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Effects of Ire1 gene on virulence and pathogenicity of Candida albicans

  • Huihai Zhao , Lixia Qin , Mengyan Li , Mengyu Jiang , Mengge Cui , Hua Wang , Baohua Hou , Fukun Wang EMAIL logo and Keran Jia EMAIL logo
Published/Copyright: April 29, 2025
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Open Life Sciences
From the journal Open Life Sciences Volume 20 Issue 1

Abstract

With the extensive utilization of antifungal drugs, the drug resistance of Candida albicans is progressively intensifying, and the effect of empirical treatment for C. albicans infection is not evident. There is an urgent need for novel strategies and methods for the treatment of C. albicans infection. Our study utilized the previously constructed C. albicans Ire1 double gene deletion strain to explore the influence of the Ire1 on endoplasmic reticulum (ER) stress and pathogenicity of C. albicans through drug stress phenotype testing, biofilm and hyphomycete formation testing, and mouse systemic infection testing. The results indicate that Ire1 is involved in maintaining the integrity of the C. albicans cell wall and influencing the hyphal formation ability of C. albicans. Concurrently, the deletion of the Ire1 increased the sensitivity of C. albicans to the ER stress agents tunicamycin and dithiothreitol and diminished the biofilm formation ability of C. albicans in vitro, resulting in significant inhibition of the growth of C. albicans. In mouse models, the deletion of Ire1 completely nullified the virulence and pathogenicity of C. albicans in the tail vein infection. In conclusion, Ire1 might be a key target for the potential development of new therapeutic drugs and vaccines.

Keywords: Candida albicans ; Ire1; endoplasmic reticulum; virulence

1 Introduction

Candida is an opportunistic pathogen that is prevalently present in the peripheral environment and constitutes the microflora of normal human skin and gut, with a carriage rate reaching up to 60% in healthy individuals [1,2,3,4].

Candidiasis typically occurs as a consequence of excessive proliferation or abnormal colonization of candidiasis due to local or general impairments in the host’s defense mechanisms [3]. In recent years, with the advancement of science and technology, medical conditions and the medical environment have continued to improve; however, this has been accompanied by an increase in the incidence and mortality of invasive candidiasis, with a crude mortality rate of 46–75% and an attributable mortality rate of 10–49% [1,5,6,7,8]; thus, it has drawn extensive concern from clinicians.

With the extensive utilization of antifungal drugs, the drug resistance of Candida albicans is also escalating [9,10,11,12,13,14]. The efficacy of empirical treatment for C. albicans infection is not conspicuous, and novel strategies for the treatment of C. albicans infection are urgently required in the clinical setting. Hence, to explore the virulence factors and/or pathogenic factors of C. albicans to identify new key targets and provide a theoretical foundation for the discovery and development of new therapeutic drugs and vaccines.

2 Materials and methods

2.1 Strains and reagents

The standard strains SN152 and Ire1 gene knockout strains (Ire1Δ/Δ) of C. albicans were maintained in the laboratory of Bethune International Peace Hospital. Yeast extract and peptone were purchased from OXOID company; YPD culture medium (self-prepared), RPMI-1640, and d-anhydrous glucose were obtained from Solarbio; agar powder was purchased from Beijing Aoboxing; fluconazole (FLU), itraconazole (ITZ), calcium fluoride white (CFW), and Congo red (CGR) were purchased from MCE.

  1. Informed consent: Informed consent has been obtained from all individuals included in this study.

  2. Ethical approval: The research related to human use has been complied with all the relevant national regulations and institutional policies and in accordance with the tenets of the Helsinki Declaration and has been approved by the Ethics Committee of the 980Th Hospital of PLA Joint Logistical Support Force (Bethune International Peace Hospital) (2023-KY-93).

2.2 Methods

2.2.1 Activation of C. albicans

Standard strains SN152 and Ire1Δ/Δ and clinical strains of C. albicans were resuscitated and inoculated onto Candida Comagia chromogenic medium and then cultured at 35°C and 5% CO2 for 48 h. A single colony with green, smooth, and good independent growth on the Candida Comagia chromogenic medium was selected using an aseptic inoculation ring and inoculated into 5 mL of YPD medium. The colony was fully mixed in a vortex mixer and incubated overnight in a shaker at 35°C at 160 rpm so that it was in the logarithmic growth phase.

2.2.2 Experiment on liquid growth of C. albicans

  1. C. albicans strains SN152 and Ire1Δ/Δ were added to 5 mL YPD, respectively, activated in a constant temperature shaking table at 35°C overnight, and then, the initial value of OD600 was adjusted to 0.1 with fresh YPD, which was evenly divided into two 50 mL sterile centrifuge tubes.

  2. Adding 2 μg/mL tunicamycin to one tube and not adding to the other tube, cultured for 20 h.

  3. Determining the strain of OD600 value and understand the strain growth situation.

2.2.3 Liquid mycelium induction of C. albicans

The overnight-activated C. albicans SN152 and Ire1Δ/Δ strains were collected by centrifuge at 5,000 rpm. The bacteria were washed with sterile phosphate buffered saline (PBS) for 2–3 times and then re-suspended in the mycelium induction medium with RPMI 1640, with the initial OD600 adjusted to approximately 0.05. After incubation at 160 rpm in a constant temperature shaking table at 35°C for 2 h, the bacteria were collected, and the mycelial growth status of each strain was observed by wet tablets and Gram staining microscopy.

2.2.4 The ability of C. albicans to form biofilm in vitro was detected by crystal violet staining

The activated C. albicans SN152 and Ire1Δ/Δ strains were collected by centrifugation at 5,000 rpm, washed with sterile PBS for 2–3 times, and then re-suspended in RPMI 1640 medium. The initial OD600 was adjusted to approximately 0.1, and 100 μL/well was added to the 96-well plate. After 24 h culture, the culture medium was aspirated and washed with 200 μL/well PBS for 3 times. After fixation with 100 μL/well methanol for 15 min, the methanol was aspirated and allowed to dry. After staining with 100 μL/well 1% crystal violet for 5 min, the remaining crystal violet was aspirated and washed with 200 μL/well PBS several times until rinsed. The plate was dried upside down in a 37°C incubator. 100 μL/well of 33% glacial acetic acid was dissolved at 37°C for 30 min and mixed well. The OD595 value was detected and recorded.

2.2.5 Determination of C. albicans stress phenotype

The growth of C. albicans SN152 and Ire1Δ/Δ under diverse pressure conditions was observed through spot testing.

  1. C. albicans SN152 and Ire1Δ/Δ were, respectively, added to 5 mL YPD and were oscillated overnight in a constant temperature shaking table at 35°C for activation. Subsequently, the OD600 value of the bacterial solution was adjusted to approximately 0.1 with fresh YPD and was cultured at 160 rpm in a shaking table at 35°C for 4–6 h to reach the logarithmic stage.

  2. The bacteria reaching the logarithmic stage were centrifuged and collected at 5,000 rpm. Then, the centrifuged bacteria were washed with sterile normal saline for 2–3 times, suspended in the normal saline, and the OD600 was adjusted to 0.2.

  3. Dilute OD600 to 0.2 bacterial solution by double ratio (10 times gradient) and dilute four gradients.

  4. Take 2.5 μL of the bacterial solution per gradient, place it on the labeled solid pressure medium plate in the order of points from high to low concentration, and seal the plate with a sealing film.

  5. The plate was placed upside down in a constant temperature and humidity incubator at 35°C for approximately 2–3 days. Subsequently, the growth of each strain was observed and photographed for record keeping.

2.2.6 Determination of systemic infection ability in mice

  1. Seven-week-old female BALB/C mice were randomly divided into the normal saline group, the SN152 group, and the Ire1Δ/Δ group (nine mice per group) for the subsequent establishment of the experimental model via tail vein injection.

  2. The overnight-activated C. albicans SN152 and Ire1Δ/Δ strains were collected by centrifugation at 5,000 rpm, washed with sterile normal saline for 2–3 times, and then suspended in sterile normal saline and adjusted to an OD600 of 0.5 (approximately 5 × 107 CFU/mL). The suspension of C. albicans was injected into the tail vein of each group of mice through tail vein injection, 100 μL each (5 × 106 CFU/mL).

  3. The growth and death of mice in each group were periodically recorded starting from the second day after the completion of the tail vein injection. The death data of mice in each group were statistically analyzed, and the survival curve was drawn using GraphPad Prism 9 software.

  4. On the second day following the tail vein injection, four mice in each group were killed by neck amputation. Subsequently, the right kidney was dissected, washed with sterile PBS, weighed, placed in a 1 mL sterile PBS EP tube, and homogenized with an ultrasonic breaker. The homogenate was diluted by multiple (10-fold) gradients, and 10 μL was applied onto a Candida chromogenic plate. After incubation at 35°C for 2–3 days, the number of C. albicans colonies on the plate was counted, and the load of C. albicans in mouse kidneys was calculated to indicate the colonization ability of C. albicans SN152 and Ire1Δ/Δ in mouse kidneys.

2.2.7 Pathological evaluation of mouse renal tissue injury

  1. The operation was identical to that in Section 2.2.6. After dissection, the left kidney was retrieved, promptly placed in neutral buffered formalin, labeled, and fixed at room temperature for 24 h.

  2. Preparation of slices

    Slice and patch: The embedded wax blocks are sliced into 3–5 μm sections using a microslicer and then placed in a constant-temperature water bath. The sections are tightly pressed onto the pathological slides with tweezers, dried in a 45°C incubator, and sealed with neutral gum after staining.

  3. Hematoxylin–eosin (HE) staining

  4. Glycogen (PAS) staining

3 Results

3.1 Deletion of Ire1 affects the stress function of the endoplasmic reticulum (ER) of C. albicans

ER stress refers to the accumulation of unfolded or misfolded proteins in the ER caused by various reasons, which triggers the unfolded protein response [15,16,17]. Itamycin and dithiothreitol (DTT) can serve as an inducer of ER stress, resulting in a significant accumulation of misfolded proteins [18]. To explore the effect of Ire1 gene deletion on the ER function of C. albicans, we performed a DTT sensitive phenotype test of C. albicans SN152 (WT) and the Ire1 gene deletion strain Ire1Δ/Δ to 2 μg/mL itamycin and 20 μM by using the solid dilution point plate method. The phenotypic results are presented in Figure 1. According to the results, there was no difference in the growth of C. albicans in the SN152 (WT) group and the Ire1Δ/Δ group on the solid YPD plate.

Figure 1 Growth phenotypes of SN152, Ire1Δ/Δ strains on (a) YPD, (b) 2 μg/mL tunicamycin, and (c) (20 μM DTT) drug plates.
Figure 1

Growth phenotypes of SN152, Ire1Δ/Δ strains on (a) YPD, (b) 2 μg/mL tunicamycin, and (c) (20 μM DTT) drug plates.

However, after 2–3 days of culture with 2 μg/mL of eimycin and 20 μM of DTT, compared with the SN152 (WT) strain, the deletion of Ire1Δ/Δ strain was significantly more sensitive to 2 μg/mL of itamycin and 20 μM of DTT, and its growth was significantly inhibited.

Meanwhile, the growth of the SN152 (WT) and Ire1Δ/Δ strains was measured through a liquid growth test. The phenotypic results are presented in Figure 2. After adding 2 μg/mL of eimycin in the YPD liquid medium for 20 h, the OD600 of Ire1Δ/Δ decreased more significantly than that of SN152 (WT) (****P < 0.0001). Therefore, we contend that the Ire1 gene is involved in maintaining the normal function of the ER stress of C. albicans.

Figure 2 Growth assay of SN152, Ire1Δ/Δ strains in YPD liquid medium containing tunicamycin (2 μg/mL).
Figure 2

Growth assay of SN152, Ire1Δ/Δ strains in YPD liquid medium containing tunicamycin (2 μg/mL).

3.2 The impact of Ire1 deletion on the transformation function of C. albicans yeast to mycelium

C. albicans is a typical dimorphic fungus that exhibits a variety of forms, such as yeast, pseudomycelium, and mycelium. It can switch between the yeast phase, the mycelium phase, and the pseudomycelium phase, and this morphological transformation is closely related to the virulence of C. albicans [3,19,20].

When the host immunity is low, the form of C. albicans undergoes a change, transforming from the yeast form to the mycelium form. The corresponding adhesion and invasion are enhanced, and it becomes easier to penetrate the host mucosal barrier, eventually causing invasive candidiasis. In severe cases, it may even threaten the life of the host.

SN152 (WT) and Ire1Δ/Δ strains were activated overnight and cultivated in RPMI 1640 mycelia induction medium at 37°C for 2 h. Subsequently, the mycelia development capacity of each strain was observed under the microscope through wet tablets and Gram staining. As depicted in Figure 3, the mycelium of the SN152 (WT) strain could develop normally after a 2-h culture. In contrast to the wild strain, yeast-type cells were the dominant morphology in the Ire1Δ/Δ strain, and only a few spores developed short mycelia presenting a pseudomycelia state. These results imply that the deletion of the Ire1 gene can severely affect the mycelial formation ability of C. albicans.

Figure 3 Effect of Ire1Δ/Δ on the ability of C. albicans to form hyphae. (a) and (b) Wet film microscopy and (c) and (d) Gram staining microscopy.
Figure 3

Effect of Ire1Δ/Δ on the ability of C. albicans to form hyphae. (a) and (b) Wet film microscopy and (c) and (d) Gram staining microscopy.

3.3 Effect of Ire1 gene knockout on biofilm formation of C. albicans in vitro

Crystal Violet dye is an alkaline dye that can bind to the DNA in the nucleus, presenting a deep purple color. This enables the number of cells in the C. albicans biofilm to be expressed by the color depth, and the biofilm is quantified by measuring its absorbance at OD595. As shown in Figure 4, compared with SN152, the ability of the Ire1Δ/Δ strain to generate a biofilm was significantly reduced. These results suggest that the deletion of the Ire1 gene has a significant impact on the biofilm formation ability of C. albicans.

Figure 4 Effect of deletion of the Ire1 gene on the ability of C. albicans to form biofilms.
Figure 4

Effect of deletion of the Ire1 gene on the ability of C. albicans to form biofilms.

3.4 Deletion of Ire1 results in an increased sensitivity to stress in the cell wall of C. albicans

The cell wall of C. albicans serves as the first barrier against host immunity and possesses multiple functions, such as secreting adhesion factors, promoting morphological transformation, and enabling biofilm formation. To detect the effect of the Ire1 gene on the formation or remodeling of the cell wall of C. albicans, we conducted solid dilution point plate experiments using cell wall stress agents, CFW, and CGR. CFW can bind to glycosides with β-links. The chitin and cellulose in the cell wall of C. albicans contain β-linked glycosides, and CFW binds to them and inhibits their synthesis. CGR can specifically bind to 1,3-β-d glucan in the cell wall of C. albicans, preventing the normal assembly of the cell wall. As shown in Figure 5, the Ire1 gene deletion strain was significantly more sensitive to the pressure plates containing CFW (50 μg/mL) and CGR (10 μg/mL) compared with the SN152 (WT) strain. This indicates that the Ire1 gene of C. albicans plays a role in the cell wall stress induced by CFW and CGR.

Figure 5 Growth phenotypes of SN152, Ire1Δ/Δ strains on (a) (YPD), (b) (50 μg/mL CFW), and (c) (10 μg/mL CGR) plates.
Figure 5

Growth phenotypes of SN152, Ire1Δ/Δ strains on (a) (YPD), (b) (50 μg/mL CFW), and (c) (10 μg/mL CGR) plates.

3.5 The Ire1 influences resistance of C. albicans to antifungal drugs

Azoles constitute a group of antifungal compounds that exhibit a broad range of activities against the majority of Candida species. They are generally well tolerated, possess predictable drug–drug interactions and can be administered either intravenously or orally as systemic drugs. The azole antifungals inhibit seosterol 14α-demethylase, which is a crucial enzyme in the formation of ergosterol, a major component of fungal cell membranes [21]. We investigated the susceptibility of C. albicans strains, SN152 (WT) and Ire1Δ/Δ, to FLU and ITZ. As depicted in Figure 6, the Ire1 deletion strain was significantly more sensitive to FLU (2 μg/mL, 4 μg/mL) and ITZ (0.125 μg/mL, 0.25 μg/mL) than the SN152 (WT) strain.

Figure 6 Growth phenotypes of SN152, Ire1Δ/Δ strains on (a) (YPD), (b) (2 μg/mL FLU), (c) (4 μg/mL FLU), (d) (0.125 μg/mL ITZ), and (e) (0.25 μg/mL ITZ) plates.
Figure 6

Growth phenotypes of SN152, Ire1Δ/Δ strains on (a) (YPD), (b) (2 μg/mL FLU), (c) (4 μg/mL FLU), (d) (0.125 μg/mL ITZ), and (e) (0.25 μg/mL ITZ) plates.

3.6 Effect of Ire1 gene deletion on the ability of C. albicans to infect systemically

The aforementioned experimental results showed that the deletion of the Ire1 gene significantly affected the mycelial formation and morphological transformation abilities of C. albicans. To further explore the effect of the Ire1 gene on C. albicans’s virulence in mice, the mouse systemic infection model was established by injecting the tail vein. For detailed information, refer to Section 2.2.12. The mice were infected with strains of C. albicans SN152 (WT) and Ire1Δ/Δ through tail vein injection at a dose of 5 × 106 per mouse.

3.6.1 Survival curve

As shown in Figure 7, mice injected with the SN152 (WT) strain began to die on the first day after injection and all died by the third day, with a 100% mortality rate. Mice injected with the Ire1Δ/Δ strain, like those in the normal saline group, grew well and none died during the 14-day observation. The results indicated that the deletion of the Ire1 gene caused C. albicans to completely lose its pathogenicity and virulence.

Figure 7 Survival curves of BALB/c mice after tail vein injection of C. albicans.
Figure 7

Survival curves of BALB/c mice after tail vein injection of C. albicans.

3.6.2 Analysis of bacterial load in kidney tissue

In the mouse model of bloodstream infection, the kidney is the main target organ attacked by C. albicans. To detect the effect of the Ire1 gene on the virulence of C. albicans infection, we counted and analyzed the bacterial amount in the kidneys of mice injected with C. albicans for 24 h. The specific operation steps are presented in Section 2.2.12. The experimental results are shown in Figure 8. After mice were infected with the C. albicans SN152 (WT) strain, the bacterial count in kidney tissue was 1.9 × 107/g, while after mice were infected with the Ire1Δ/Δ strain, the bacterial amount in kidney tissue was 0, completely losing the ability of colonization in mouse kidneys.

Figure 8 Determination of bacterial load in mouse kidney at 24 h.
Figure 8

Determination of bacterial load in mouse kidney at 24 h.

3.6.3 Pathological analysis of kidney tissue

HE and PAS staining were used to stain the kidney tissue of mice infected with C. albicans. The appearance of mouse kidney tissue is presented in Figure 9. The kidneys of C. albicans Ire1Δ/Δ and saline mice appeared reddish, while those of SN152 (WT)-infected mice appeared gray.

Figure 9 Appearance of kidney tissue in (a) saline, (b) Ire1Δ/Δ, and (c) SN152 groups.
Figure 9

Appearance of kidney tissue in (a) saline, (b) Ire1Δ/Δ, and (c) SN152 groups.

3.6.3.1 HE staining of pathological sections of kidney

The experimental results are presented in Figure 10. The Ire1Δ/Δ group and the normal saline group had normal kidney tissues, with no pathological changes or inflammatory cell infiltration observed. The pathological sections of mice infected with the SN152 (WT) strain indicated that the main pathological changes were inflammatory cell infiltration, and the renal interstitium, renal tubules, and glomeruli were invaded, dissolved, and destroyed to varying degrees.

Figure 10 HE staining of kidney tissue (a) saline, (b) Ire1Δ/Δ, and (c) SN152 groups.
Figure 10

HE staining of kidney tissue (a) saline, (b) Ire1Δ/Δ, and (c) SN152 groups.

3.6.3.2 Renal tissue PAS staining

The experimental results are presented in Figure 11. The Ire1Δ/Δ group and the normal saline group had normal kidney tissues, and no C. albicans invasion or inflammatory cell infiltration was observed. A large number of mycelial C. albicans were found in the renal tubules and calyces of mice infected with the SN152 (WT) strain. Thus, we believe that the deletion of the Ire1 gene causes C. albicans to completely lose its ability to invade mouse kidney tissue. The Ire1 gene is an important factor in maintaining the virulence of C. albicans.

Figure 11 PAS staining of kidney tissue (a) saline, (b) Ire1Δ/Δ, and (c) SN152 groups.
Figure 11

PAS staining of kidney tissue (a) saline, (b) Ire1Δ/Δ, and (c) SN152 groups.

4 Discussion

Candida is an opportunistic pathogen that exists widely in the surrounding environment and is a microflora of normal human skin and gut, with a carriage rate of up to 60% in healthy people [1]. Candidiasis usually occurs due to overpropagation or abnormal colonization of Candida as a result of local or general defects in host defense mechanisms.

Candidiasis is a broad term that encompasses fungal infections of the skin, mucous membranes, and deep organs (intraperitoneal, thoracic, bone and joint, brain, heart, kidney, liver, spleen, etc.). It can occur at any age, while invasive candidiasis mainly refers to candidemia and deep organ infection.

In recent years, with the advancement of science and technology, medical conditions and the medical environment keep improving. However, the incidence and mortality of invasive candidiasis have increased, with a crude mortality of 46–75% and an attributable mortality of 10–49% [1,5,6,7,8], which has drawn wide attention from clinicians. At least 15 distinct Candida spp. can cause human diseases, but the majority of invasive infections are caused by five pathogens: C. albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei [1,2,6,7]. The most common fungus causing invasive candidiasis infections is C. albicans. When the immune mechanism of the host is impaired or the intestinal mucosal flora is imbalanced, C. albicans can change from colonization to opportunistic bacteria and cause infection.

At present, there are three clear mechanisms causing infection: (1) long-term use of broad-spectrum antibiotics leads to flora imbalance, inhibits normal bacteria, reduces the release of mucosal anti-Candida protective factors, and causes Candida overcloning and reproduction [2,22]. (2) Damage to gastrointestinal and cutaneous mucosal barriers. Gastrointestinal surgeries, perforations, and central vein catheterizations can cause mucosal barrier damage, allowing C. albicans colonized in these sites to enter the bloodstream through the damaged mucosa. (3) The use of immunosuppressants, such as chemotherapy-induced neutropenia and glucocorticoid therapy, can reduce the host’s immune and epidemic prevention abilities, resulting in C. albicans entering tissues or organs from the blood. Common parts are the liver, spleen, kidney, brain, and heart, which may be related to the rich blood flow in these parts, increasing the chance of invasion.

At present, the drugs commonly used in clinical practice mainly include acanthocinins, azole, and polyenes. However, with the widespread use of antifungal drugs, the drug resistance of C. albicans is also increasing, and the effect of traditional treatment methods is not significant, which can no longer fully meet the needs of clinical treatment of C. albicans infection. Therefore, the virulence factors or pathogenic factors of C. albicans were studied to find new key targets and provide a theoretical basis for finding and developing new therapeutic drugs and vaccines.

The protein structure of Ire1 is the most conserved in eukaryotes, including fungal members. It acts as an ER stress sensor and plays pleiotropic roles in ER stress response, antifungal tolerance, cell wall regulation, and virulence-related traits [15,16,23]. Therefore, studying the molecular mechanism of the Ire1 pathway influencing C. albicans hyphae formation and pathogenicity by regulating ER stress will help clarify the relationship between hyphae formation and pathogenic factors at the cellular and molecular levels, and assist in finding therapeutic targets for C. albicans infection.

The Ire1 gene is highly correlated with the pathogenic virulence of C. albicans. In the ER stress induced by tunicamycin and DTT, the Ire1 deletion strain IRE1Δ/Δ exhibited greater sensitivity to 2 μg/mL tunicamycin and 20 μM DTT than the SN152 (WT) strain, and its growth was significantly inhibited. In the RPMI 1640 hyphae induction training, the hypha growth and biofilm formation ability of Ire1Δ/Δ had obvious flaws, which affected the yeast-mycelial morphological transformation and adhesion ability of C. albicans. Ire1Δ/Δ exhibited increased sensitivity to azole antifungals such as FLU and ITZ, as well as cell wall stressors CFW and CGR, illustrating the precise role of Ire1 in regulating sensitivity to these antifungals and cell wall stressors.

The Ire1Δ/Δ strain was non-virulent in the tail vein-infected mouse model and completely lost its pathogenic capacity.

All experimental mice survived until the conclusion of the experiment without manifesting clinical symptoms, and no C. albicans was cultivated from the kidney tissue of the infected mice. No invasion of C. albicans and inflammatory cell infiltration were observed in the pathological sections of the renal tissue.

5 Conclusion

In conclusion, we constructed Sho1Δ/Δ and investigated the influence of the Ire1 gene on ER stress and the pathogenicity of C. albicans through drug stress phenotype testing, biofilm formation assays, hyphal growth assays, and systemic infection tests in mice. The deletion of the Ire1 gene decreased the ability of C. albicans to form hyphae and biofilms, impaired cell wall integrity, increased sensitivity to ER stress agents, and lost toxicity in a mouse tail vein injection model. These results demonstrate that the Ire1 gene maintains the virulence and pathogenicity of C. albicans and can serve as a key target for the potential development of new therapeutic drugs and vaccines.

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  1. Funding information: This study was supported by the 980Th Hospital of PLA Joint Logistical Support Force science and technology innovation incubation plan project (FYJHQN202303) and Hebei Province medical science research project (20241197).

  2. Author contributions: Conception and design were contributed by HZ, FW, and KJ; manuscript was drafted by HZ and LQ; provision of study materials or patients was contributed by BH, KJ, and FW; all experiments were completed by HZ, ML, HW, and MJ; data analysis and interpretation were contributed by HZ, LQ, HW, MJ, and MC; and FW and KJ revised the manuscript and were the supporters of the study. All authors contributed to the article and approved the submitted version.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2024-08-03
Revised: 2024-12-02
Accepted: 2025-01-16
Published Online: 2025-04-29

© 2025 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Biomedical Sciences
  2. Mechanism of triptolide regulating proliferation and apoptosis of hepatoma cells by inhibiting JAK/STAT pathway
  3. Maslinic acid improves mitochondrial function and inhibits oxidative stress and autophagy in human gastric smooth muscle cells
  4. Comparative analysis of inflammatory biomarkers for the diagnosis of neonatal sepsis: IL-6, IL-8, SAA, CRP, and PCT
  5. Post-pandemic insights on COVID-19 and premature ovarian insufficiency
  6. Proteome differences of dental stem cells between permanent and deciduous teeth by data-independent acquisition proteomics
  7. Optimizing a modified cetyltrimethylammonium bromide protocol for fungal DNA extraction: Insights from multilocus gene amplification
  8. Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
  9. Efficacy of alginate-coated gold nanoparticles against antibiotics-resistant Staphylococcus and Streptococcus pathogens of acne origins
  10. Battling COVID-19 leveraging nanobiotechnology: Gold and silver nanoparticle–B-escin conjugates as SARS-CoV-2 inhibitors
  11. Neurodegenerative diseases and neuroinflammation-induced apoptosis
  12. Impact of fracture fixation surgery on cognitive function and the gut microbiota in mice with a history of stroke
  13. COLEC10: A potential tumor suppressor and prognostic biomarker in hepatocellular carcinoma through modulation of EMT and PI3K-AKT pathways
  14. High-temperature requirement serine protease A2 inhibitor UCF-101 ameliorates damaged neurons in traumatic brain-injured rats by the AMPK/NF-κB pathway
  15. SIK1 inhibits IL-1β-stimulated cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling
  16. Rutin–chitooligosaccharide complex: Comprehensive evaluation of its anti-inflammatory and analgesic properties in vitro and in vivo
  17. Knockdown of Aurora kinase B alleviates high glucose-triggered trophoblast cells damage and inflammation during gestational diabetes
  18. Calcium-sensing receptors promoted Homer1 expression and osteogenic differentiation in bone marrow mesenchymal stem cells
  19. ABI3BP can inhibit the proliferation, invasion, and epithelial–mesenchymal transition of non-small-cell lung cancer cells
  20. Changes in blood glucose and metabolism in hyperuricemia mice
  21. Rapid detection of the GJB2 c.235delC mutation based on CRISPR-Cas13a combined with lateral flow dipstick
  22. IL-11 promotes Ang II-induced autophagy inhibition and mitochondrial dysfunction in atrial fibroblasts
  23. Short-chain fatty acid attenuates intestinal inflammation by regulation of gut microbial composition in antibiotic-associated diarrhea
  24. Application of metagenomic next-generation sequencing in the diagnosis of pathogens in patients with diabetes complicated by community-acquired pneumonia
  25. NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation
  26. Phytol-mixed micelles alleviate dexamethasone-induced osteoporosis in zebrafish: Activation of the MMP3–OPN–MAPK pathway-mediating bone remodeling
  27. Association between TGF-β1 and β-catenin expression in the vaginal wall of patients with pelvic organ prolapse
  28. Primary pleomorphic liposarcoma involving bilateral ovaries: Case report and literature review
  29. Effects of de novo donor-specific Class I and II antibodies on graft outcomes after liver transplantation: A pilot cohort study
  30. Sleep architecture in Alzheimer’s disease continuum: The deep sleep question
  31. Ephedra fragilis plant extract: A groundbreaking corrosion inhibitor for mild steel in acidic environments – electrochemical, EDX, DFT, and Monte Carlo studies
  32. Langerhans cell histiocytosis in an adult patient with upper jaw and pulmonary involvement: A case report
  33. Inhibition of mast cell activation by Jaranol-targeted Pirin ameliorates allergic responses in mouse allergic rhinitis
  34. Aeromonas veronii-induced septic arthritis of the hip in a child with acute lymphoblastic leukemia
  35. Clusterin activates the heat shock response via the PI3K/Akt pathway to protect cardiomyocytes from high-temperature-induced apoptosis
  36. Research progress on fecal microbiota transplantation in tumor prevention and treatment
  37. Low-pressure exposure influences the development of HAPE
  38. Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis
  39. AKAP12, mediated by transcription factor 21, inhibits cell proliferation, metastasis, and glycolysis in lung squamous cell carcinoma
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  41. A case of bloodstream infection caused by Neisseria gonorrhoeae
  42. Case of nasopharyngeal tuberculosis complicated with cervical lymph node and pulmonary tuberculosis
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  52. The effect of the PKR inhibitor, 2-aminopurine, on the replication of influenza A virus, and segment 8 mRNA splicing
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  54. Small cell lung cancer with small intestinal metastasis: Case report and literature review
  55. GRB14: A prognostic biomarker driving tumor progression in gastric cancer through the PI3K/AKT signaling pathway by interacting with COBLL1
  56. 15-Lipoxygenase-2 deficiency induces foam cell formation that can be restored by salidroside through the inhibition of arachidonic acid effects
  57. FTO alleviated the diabetic nephropathy progression by regulating the N6-methyladenosine levels of DACT1
  58. Clinical relevance of inflammatory markers in the evaluation of severity of ulcerative colitis: A retrospective study
  59. Zinc valproic acid complex promotes osteoblast differentiation and exhibits anti-osteoporotic potential
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  61. Metagenomic next-generation sequencing of alveolar lavage fluid improves the detection of pulmonary infection
  62. Uterine tumor resembling ovarian sex cord tumor with extensive rhabdoid differentiation: A case report
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  64. Effects of tiered cardiac rehabilitation on CRP, TNF-α, and physical endurance in older adults with coronary heart disease
  65. Changes in T-lymphocyte subpopulations in patients with colorectal cancer before and after acupoint catgut embedding acupuncture observation
  66. Modulating the tumor microenvironment: The role of traditional Chinese medicine in improving lung cancer treatment
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  68. Research on individualized drug sensitivity detection technology based on bio-3D printing technology for precision treatment of gastrointestinal stromal tumors
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  70. Oncolytic bacteria: A revolutionary approach to cancer therapy
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  72. Diagnosis of secondary tuberculosis infection in an asymptomatic elderly with cancer using next-generation sequencing: Case report
  73. Hesperidin and its zinc(ii) complex enhance osteoblast differentiation and bone formation: In vitro and in vivo evaluations
  74. Research progress on the regulation of autophagy in cardiovascular diseases by chemokines
  75. Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
  76. Immunoassay for pyruvate kinase M1/2 as an Alzheimer’s biomarker in CSF
  77. The role of HDAC11 in age-related hearing loss: Mechanisms and therapeutic implications
  78. Evaluation and application analysis of animal models of PIPNP based on data mining
  79. Therapeutic approaches for liver fibrosis/cirrhosis by targeting pyroptosis
  80. Fabrication of zinc oxide nanoparticles using Ruellia tuberosa leaf extract induces apoptosis through P53 and STAT3 signalling pathways in prostate cancer cells
  81. Haplo-hematopoietic stem cell transplantation and immunoradiotherapy for severe aplastic anemia complicated with nasopharyngeal carcinoma: A case report
  82. Modulation of the KEAP1-NRF2 pathway by Erianin: A novel approach to reduce psoriasiform inflammation and inflammatory signaling
  83. The expression of epidermal growth factor receptor 2 and its relationship with tumor-infiltrating lymphocytes and clinical pathological features in breast cancer patients
  84. Innovations in MALDI-TOF Mass Spectrometry: Bridging modern diagnostics and historical insights
  85. BAP1 complexes with YY1 and RBBP7 and its downstream targets in ccRCC cells
  86. Hypereosinophilic syndrome with elevated IgG4 and T-cell clonality: A report of two cases
  87. Electroacupuncture alleviates sciatic nerve injury in sciatica rats by regulating BDNF and NGF levels, myelin sheath degradation, and autophagy
  88. Polydatin prevents cholesterol gallstone formation by regulating cholesterol metabolism via PPAR-γ signaling
  89. RNF144A and RNF144B: Important molecules for health
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  91. Artesunate inhibits hepatocellular carcinoma cell migration and invasion through OGA-mediated O-GlcNAcylation of ZEB1
  92. Endovascular management of post-pancreatectomy hemorrhage caused by a hepatic artery pseudoaneurysm: Case report and review of the literature
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  94. SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
  95. Overexpression of the ferroptosis-related gene, NFS1, corresponds to gastric cancer growth and tumor immune infiltration
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  97. Atractylenolide I alleviates the experimental allergic response in mice by suppressing TLR4/NF-kB/NLRP3 signalling
  98. FBXO31 inhibits the stemness characteristics of CD147 (+) melanoma stem cells
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  100. Inhibiting CXCR6 promotes senescence of activated hepatic stellate cells with limited proinflammatory SASP to attenuate hepatic fibrosis
  101. Cadmium toxicity, health risk and its remediation using low-cost biochar adsorbents
  102. Pulmonary cryptococcosis with headache as the first presentation: A case report
  103. Solitary pulmonary metastasis with cystic airspaces in colon cancer: A rare case report
  104. RUNX1 promotes denervation-induced muscle atrophy by activating the JUNB/NF-κB pathway and driving M1 macrophage polarization
  105. Morphometric analysis and immunobiological investigation of Indigofera oblongifolia on the infected lung with Plasmodium chabaudi
  106. The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
  107. Experimental study on salmon demineralized bone matrix loaded with recombinant human bone morphogenetic protein-2: In vitro and in vivo study
  108. A case of IgA nephropathy treated with a combination of telitacicept and half-dose glucocorticoids
  109. Analgesic and toxicological evaluation of cannabidiol-rich Moroccan Cannabis sativa L. (Khardala variety) extract: Evidence from an in vivo and in silico study
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  114. Optimization and comparative study of Bacillus consortia for cellulolytic potential and cellulase enzyme activity
  115. The complete mitochondrial genome analysis of Haemaphysalis hystricis Supino, 1897 (Ixodida: Ixodidae) and its phylogenetic implications
  116. Epidemiological characteristics and risk factors analysis of multidrug-resistant tuberculosis among tuberculosis population in Huzhou City, Eastern China
  117. Indices of human impacts on landscapes: How do they reflect the proportions of natural habitats?
  118. Genetic analysis of the Siberian flying squirrel population in the northern Changbai Mountains, Northeast China: Insights into population status and conservation
  119. Diversity and environmental drivers of Suillus communities in Pinus sylvestris var. mongolica forests of Inner Mongolia
  120. Agriculture
  121. Integrated analysis of transcriptome, sRNAome, and degradome involved in the drought-response of maize Zhengdan958
  122. Variation in flower frost tolerance among seven apple cultivars and transcriptome response patterns in two contrastingly frost-tolerant selected cultivars
  123. Heritability of durable resistance to stripe rust in bread wheat (Triticum aestivum L.)
  124. Animal Science
  125. Effect of sex ratio on the life history traits of an important invasive species, Spodoptera frugiperda
  126. Plant Sciences
  127. Hairpin in a haystack: In silico identification and characterization of plant-conserved microRNA in Rafflesiaceae
  128. Widely targeted metabolomics of different tissues in Rubus corchorifolius
  129. The complete chloroplast genome of Gerbera piloselloides (L.) Cass., 1820 (Carduoideae, Asteraceae) and its phylogenetic analysis
  130. Field trial to correlate mineral solubilization activity of Pseudomonas aeruginosa and biochemical content of groundnut plants
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  139. Review on role of honey in disease prevention and treatment through modulation of biological activities
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  143. Toxicological qualities and detoxification trends of fruit by-products for valorization: A review
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  150. Impact of hyaluronic acid-modified hafnium metalorganic frameworks containing rhynchophylline on Alzheimer’s disease
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https://doi.org/10.1515/biol-2022-1062
Keywords for this article
Candida albicans; Ire1; endoplasmic reticulum; virulence
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Mechanism of triptolide regulating proliferation and apoptosis of hepatoma cells by inhibiting JAK/STAT pathway
  3. Maslinic acid improves mitochondrial function and inhibits oxidative stress and autophagy in human gastric smooth muscle cells
  4. Comparative analysis of inflammatory biomarkers for the diagnosis of neonatal sepsis: IL-6, IL-8, SAA, CRP, and PCT
  5. Post-pandemic insights on COVID-19 and premature ovarian insufficiency
  6. Proteome differences of dental stem cells between permanent and deciduous teeth by data-independent acquisition proteomics
  7. Optimizing a modified cetyltrimethylammonium bromide protocol for fungal DNA extraction: Insights from multilocus gene amplification
  8. Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
  9. Efficacy of alginate-coated gold nanoparticles against antibiotics-resistant Staphylococcus and Streptococcus pathogens of acne origins
  10. Battling COVID-19 leveraging nanobiotechnology: Gold and silver nanoparticle–B-escin conjugates as SARS-CoV-2 inhibitors
  11. Neurodegenerative diseases and neuroinflammation-induced apoptosis
  12. Impact of fracture fixation surgery on cognitive function and the gut microbiota in mice with a history of stroke
  13. COLEC10: A potential tumor suppressor and prognostic biomarker in hepatocellular carcinoma through modulation of EMT and PI3K-AKT pathways
  14. High-temperature requirement serine protease A2 inhibitor UCF-101 ameliorates damaged neurons in traumatic brain-injured rats by the AMPK/NF-κB pathway
  15. SIK1 inhibits IL-1β-stimulated cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling
  16. Rutin–chitooligosaccharide complex: Comprehensive evaluation of its anti-inflammatory and analgesic properties in vitro and in vivo
  17. Knockdown of Aurora kinase B alleviates high glucose-triggered trophoblast cells damage and inflammation during gestational diabetes
  18. Calcium-sensing receptors promoted Homer1 expression and osteogenic differentiation in bone marrow mesenchymal stem cells
  19. ABI3BP can inhibit the proliferation, invasion, and epithelial–mesenchymal transition of non-small-cell lung cancer cells
  20. Changes in blood glucose and metabolism in hyperuricemia mice
  21. Rapid detection of the GJB2 c.235delC mutation based on CRISPR-Cas13a combined with lateral flow dipstick
  22. IL-11 promotes Ang II-induced autophagy inhibition and mitochondrial dysfunction in atrial fibroblasts
  23. Short-chain fatty acid attenuates intestinal inflammation by regulation of gut microbial composition in antibiotic-associated diarrhea
  24. Application of metagenomic next-generation sequencing in the diagnosis of pathogens in patients with diabetes complicated by community-acquired pneumonia
  25. NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation
  26. Phytol-mixed micelles alleviate dexamethasone-induced osteoporosis in zebrafish: Activation of the MMP3–OPN–MAPK pathway-mediating bone remodeling
  27. Association between TGF-β1 and β-catenin expression in the vaginal wall of patients with pelvic organ prolapse
  28. Primary pleomorphic liposarcoma involving bilateral ovaries: Case report and literature review
  29. Effects of de novo donor-specific Class I and II antibodies on graft outcomes after liver transplantation: A pilot cohort study
  30. Sleep architecture in Alzheimer’s disease continuum: The deep sleep question
  31. Ephedra fragilis plant extract: A groundbreaking corrosion inhibitor for mild steel in acidic environments – electrochemical, EDX, DFT, and Monte Carlo studies
  32. Langerhans cell histiocytosis in an adult patient with upper jaw and pulmonary involvement: A case report
  33. Inhibition of mast cell activation by Jaranol-targeted Pirin ameliorates allergic responses in mouse allergic rhinitis
  34. Aeromonas veronii-induced septic arthritis of the hip in a child with acute lymphoblastic leukemia
  35. Clusterin activates the heat shock response via the PI3K/Akt pathway to protect cardiomyocytes from high-temperature-induced apoptosis
  36. Research progress on fecal microbiota transplantation in tumor prevention and treatment
  37. Low-pressure exposure influences the development of HAPE
  38. Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis
  39. AKAP12, mediated by transcription factor 21, inhibits cell proliferation, metastasis, and glycolysis in lung squamous cell carcinoma
  40. Association between PAX9 or MSX1 gene polymorphism and tooth agenesis risk: A meta-analysis
  41. A case of bloodstream infection caused by Neisseria gonorrhoeae
  42. Case of nasopharyngeal tuberculosis complicated with cervical lymph node and pulmonary tuberculosis
  43. p-Cymene inhibits pro-fibrotic and inflammatory mediators to prevent hepatic dysfunction
  44. GFPT2 promotes paclitaxel resistance in epithelial ovarian cancer cells via activating NF-κB signaling pathway
  45. Transfer RNA-derived fragment tRF-36 modulates varicose vein progression via human vascular smooth muscle cell Notch signaling
  46. RTA-408 attenuates the hepatic ischemia reperfusion injury in mice possibly by activating the Nrf2/HO-1 signaling pathway
  47. Decreased serum TIMP4 levels in patients with rheumatoid arthritis
  48. Sirt1 protects lupus nephritis by inhibiting the NLRP3 signaling pathway in human glomerular mesangial cells
  49. Sodium butyrate aids brain injury repair in neonatal rats
  50. Interaction of MTHFR polymorphism with PAX1 methylation in cervical cancer
  51. Convallatoxin inhibits proliferation and angiogenesis of glioma cells via regulating JAK/STAT3 pathway
  52. The effect of the PKR inhibitor, 2-aminopurine, on the replication of influenza A virus, and segment 8 mRNA splicing
  53. Effects of Ire1 gene on virulence and pathogenicity of Candida albicans
  54. Small cell lung cancer with small intestinal metastasis: Case report and literature review
  55. GRB14: A prognostic biomarker driving tumor progression in gastric cancer through the PI3K/AKT signaling pathway by interacting with COBLL1
  56. 15-Lipoxygenase-2 deficiency induces foam cell formation that can be restored by salidroside through the inhibition of arachidonic acid effects
  57. FTO alleviated the diabetic nephropathy progression by regulating the N6-methyladenosine levels of DACT1
  58. Clinical relevance of inflammatory markers in the evaluation of severity of ulcerative colitis: A retrospective study
  59. Zinc valproic acid complex promotes osteoblast differentiation and exhibits anti-osteoporotic potential
  60. Primary pulmonary synovial sarcoma in the bronchial cavity: A case report
  61. Metagenomic next-generation sequencing of alveolar lavage fluid improves the detection of pulmonary infection
  62. Uterine tumor resembling ovarian sex cord tumor with extensive rhabdoid differentiation: A case report
  63. Genomic analysis of a novel ST11(PR34365) Clostridioides difficile strain isolated from the human fecal of a CDI patient in Guizhou, China
  64. Effects of tiered cardiac rehabilitation on CRP, TNF-α, and physical endurance in older adults with coronary heart disease
  65. Changes in T-lymphocyte subpopulations in patients with colorectal cancer before and after acupoint catgut embedding acupuncture observation
  66. Modulating the tumor microenvironment: The role of traditional Chinese medicine in improving lung cancer treatment
  67. Alterations of metabolites related to microbiota–gut–brain axis in plasma of colon cancer, esophageal cancer, stomach cancer, and lung cancer patients
  68. Research on individualized drug sensitivity detection technology based on bio-3D printing technology for precision treatment of gastrointestinal stromal tumors
  69. CEBPB promotes ulcerative colitis-associated colorectal cancer by stimulating tumor growth and activating the NF-κB/STAT3 signaling pathway
  70. Oncolytic bacteria: A revolutionary approach to cancer therapy
  71. A de novo meningioma with rapid growth: A possible malignancy imposter?
  72. Diagnosis of secondary tuberculosis infection in an asymptomatic elderly with cancer using next-generation sequencing: Case report
  73. Hesperidin and its zinc(ii) complex enhance osteoblast differentiation and bone formation: In vitro and in vivo evaluations
  74. Research progress on the regulation of autophagy in cardiovascular diseases by chemokines
  75. Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
  76. Immunoassay for pyruvate kinase M1/2 as an Alzheimer’s biomarker in CSF
  77. The role of HDAC11 in age-related hearing loss: Mechanisms and therapeutic implications
  78. Evaluation and application analysis of animal models of PIPNP based on data mining
  79. Therapeutic approaches for liver fibrosis/cirrhosis by targeting pyroptosis
  80. Fabrication of zinc oxide nanoparticles using Ruellia tuberosa leaf extract induces apoptosis through P53 and STAT3 signalling pathways in prostate cancer cells
  81. Haplo-hematopoietic stem cell transplantation and immunoradiotherapy for severe aplastic anemia complicated with nasopharyngeal carcinoma: A case report
  82. Modulation of the KEAP1-NRF2 pathway by Erianin: A novel approach to reduce psoriasiform inflammation and inflammatory signaling
  83. The expression of epidermal growth factor receptor 2 and its relationship with tumor-infiltrating lymphocytes and clinical pathological features in breast cancer patients
  84. Innovations in MALDI-TOF Mass Spectrometry: Bridging modern diagnostics and historical insights
  85. BAP1 complexes with YY1 and RBBP7 and its downstream targets in ccRCC cells
  86. Hypereosinophilic syndrome with elevated IgG4 and T-cell clonality: A report of two cases
  87. Electroacupuncture alleviates sciatic nerve injury in sciatica rats by regulating BDNF and NGF levels, myelin sheath degradation, and autophagy
  88. Polydatin prevents cholesterol gallstone formation by regulating cholesterol metabolism via PPAR-γ signaling
  89. RNF144A and RNF144B: Important molecules for health
  90. Analysis of the detection rate and related factors of thyroid nodules in the healthy population
  91. Artesunate inhibits hepatocellular carcinoma cell migration and invasion through OGA-mediated O-GlcNAcylation of ZEB1
  92. Endovascular management of post-pancreatectomy hemorrhage caused by a hepatic artery pseudoaneurysm: Case report and review of the literature
  93. Efficacy and safety of anti-PD-1/PD-L1 antibodies in patients with relapsed refractory diffuse large B-cell lymphoma: A meta-analysis
  94. SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
  95. Overexpression of the ferroptosis-related gene, NFS1, corresponds to gastric cancer growth and tumor immune infiltration
  96. Understanding risk factors and prognosis in diabetic foot ulcers
  97. Atractylenolide I alleviates the experimental allergic response in mice by suppressing TLR4/NF-kB/NLRP3 signalling
  98. FBXO31 inhibits the stemness characteristics of CD147 (+) melanoma stem cells
  99. Immune molecule diagnostics in colorectal cancer: CCL2 and CXCL11
  100. Inhibiting CXCR6 promotes senescence of activated hepatic stellate cells with limited proinflammatory SASP to attenuate hepatic fibrosis
  101. Cadmium toxicity, health risk and its remediation using low-cost biochar adsorbents
  102. Pulmonary cryptococcosis with headache as the first presentation: A case report
  103. Solitary pulmonary metastasis with cystic airspaces in colon cancer: A rare case report
  104. RUNX1 promotes denervation-induced muscle atrophy by activating the JUNB/NF-κB pathway and driving M1 macrophage polarization
  105. Morphometric analysis and immunobiological investigation of Indigofera oblongifolia on the infected lung with Plasmodium chabaudi
  106. The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
  107. Experimental study on salmon demineralized bone matrix loaded with recombinant human bone morphogenetic protein-2: In vitro and in vivo study
  108. A case of IgA nephropathy treated with a combination of telitacicept and half-dose glucocorticoids
  109. Analgesic and toxicological evaluation of cannabidiol-rich Moroccan Cannabis sativa L. (Khardala variety) extract: Evidence from an in vivo and in silico study
  110. Wound healing and signaling pathways
  111. Combination of immunotherapy and whole-brain radiotherapy on prognosis of patients with multiple brain metastases: A retrospective cohort study
  112. To explore the relationship between endometrial hyperemia and polycystic ovary syndrome
  113. Ecology and Environmental Science
  114. Optimization and comparative study of Bacillus consortia for cellulolytic potential and cellulase enzyme activity
  115. The complete mitochondrial genome analysis of Haemaphysalis hystricis Supino, 1897 (Ixodida: Ixodidae) and its phylogenetic implications
  116. Epidemiological characteristics and risk factors analysis of multidrug-resistant tuberculosis among tuberculosis population in Huzhou City, Eastern China
  117. Indices of human impacts on landscapes: How do they reflect the proportions of natural habitats?
  118. Genetic analysis of the Siberian flying squirrel population in the northern Changbai Mountains, Northeast China: Insights into population status and conservation
  119. Diversity and environmental drivers of Suillus communities in Pinus sylvestris var. mongolica forests of Inner Mongolia
  120. Agriculture
  121. Integrated analysis of transcriptome, sRNAome, and degradome involved in the drought-response of maize Zhengdan958
  122. Variation in flower frost tolerance among seven apple cultivars and transcriptome response patterns in two contrastingly frost-tolerant selected cultivars
  123. Heritability of durable resistance to stripe rust in bread wheat (Triticum aestivum L.)
  124. Animal Science
  125. Effect of sex ratio on the life history traits of an important invasive species, Spodoptera frugiperda
  126. Plant Sciences
  127. Hairpin in a haystack: In silico identification and characterization of plant-conserved microRNA in Rafflesiaceae
  128. Widely targeted metabolomics of different tissues in Rubus corchorifolius
  129. The complete chloroplast genome of Gerbera piloselloides (L.) Cass., 1820 (Carduoideae, Asteraceae) and its phylogenetic analysis
  130. Field trial to correlate mineral solubilization activity of Pseudomonas aeruginosa and biochemical content of groundnut plants
  131. Correlation analysis between semen routine parameters and sperm DNA fragmentation index in patients with semen non-liquefaction: A retrospective study
  132. Plasticity of the anatomical traits of Rhododendron L. (Ericaceae) leaves and its implications in adaptation to the plateau environment
  133. Effects of Piriformospora indica and arbuscular mycorrhizal fungus on growth and physiology of Moringa oleifera under low-temperature stress
  134. Effects of different sources of potassium fertiliser on yield, fruit quality and nutrient absorption in “Harward” kiwifruit (Actinidia deliciosa)
  135. Comparative efficiency and residue levels of spraying programs against powdery mildew in grape varieties
  136. The DREB7 transcription factor enhances salt tolerance in soybean plants under salt stress
  137. Food Science
  138. Phytochemical analysis of Stachys iva: Discovering the optimal extract conditions and its bioactive compounds
  139. Review on role of honey in disease prevention and treatment through modulation of biological activities
  140. Computational analysis of polymorphic residues in maltose and maltotriose transporters of a wild Saccharomyces cerevisiae strain
  141. Optimization of phenolic compound extraction from Tunisian squash by-products: A sustainable approach for antioxidant and antibacterial applications
  142. Liupao tea aqueous extract alleviates dextran sulfate sodium-induced ulcerative colitis in rats by modulating the gut microbiota
  143. Toxicological qualities and detoxification trends of fruit by-products for valorization: A review
  144. Polyphenolic spectrum of cornelian cherry fruits and their health-promoting effect
  145. Optimizing the encapsulation of the refined extract of squash peels for functional food applications: A sustainable approach to reduce food waste
  146. Advancements in curcuminoid formulations: An update on bioavailability enhancement strategies curcuminoid bioavailability and formulations
  147. Impact of saline sprouting on antioxidant properties and bioactive compounds in chia seeds
  148. The dilemma of food genetics and improvement
  149. Bioengineering and Biotechnology
  150. Impact of hyaluronic acid-modified hafnium metalorganic frameworks containing rhynchophylline on Alzheimer’s disease
  151. Emerging patterns in nanoparticle-based therapeutic approaches for rheumatoid arthritis: A comprehensive bibliometric and visual analysis spanning two decades
  152. Application of CRISPR/Cas gene editing for infectious disease control in poultry
  153. Preparation of hafnium nitride-coated titanium implants by magnetron sputtering technology and evaluation of their antibacterial properties and biocompatibility
  154. Preparation and characterization of lemongrass oil nanoemulsion: Antimicrobial, antibiofilm, antioxidant, and anticancer activities
  155. Corrigendum
  156. Corrigendum to “Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells”
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