Host-derived Interleukin 1α induces an immunosuppressive tumor microenvironment via regulating monocyte-to-macrophage differentiation.

Tumor-associated macrophages exhibit high heterogeneity and contribute to the establishment of an immunosuppressive tumor microenvironment (TME). Although numerous studies have demonstrated that extracellular factors promote macrophage proliferation and polarization, the regulatory mechanisms governing the differentiation process to generate phenotypically, and functionally diverse macrophage subpopulations remain largely unexplored. In this study, we examined the influence of interleukin 1α (IL-1α) on the development of an immunosuppressive TME using orthotopic transplantation murine models of breast cancer. Deletion of host Il1α led to the rejection of inoculated congenic tumors. Single-cell sequencing analysis revealed that CX3CR1+ macrophage cells were the primary sources of IL-1α in the TME. The absence of IL-1α reprogrammed the monocyte-to-macrophage differentiation process within the TME, characterized by a notable decrease in the subset of CX3CR+ ductal-like macrophages and an increase in iNOS-expressing inflammatory cells. Comparative analysis of gene signatures in both human and mouse macrophage subsets suggested that IL-1α deficiency shifted the macrophage polarization from M2 to M1 phenotypes, leading to enhanced cytotoxic T lymphocyte activity in the TME. Importantly, elevated levels of IL-1α in human cancers were associated with worse prognosis following immunotherapy. These findings underscore the pivotal role of IL-1α in shaping an immune-suppressive TME through the regulation of macrophage differentiation and activity, highlighting IL-1α as a potential target for breast cancer treatment. Teaser: Interleukin 1α dictates macrophage behavior, influencing an immunosuppressive microenvironment in breast cancer, suggesting it as a treatment target.

Graphitic carbon nitride supported Ni-Co dual-atom catalysts beyond Ni1(Co1) single-atom catalysts for hydrogen production: a density functional theory study.

Using density functional theory calculations we investigate the formation, structure and electronic properties of gh-C3N4-supported Ni-Co (Ni-Co/gh-C3N4) dual-atom catalysts and Ni1(Co1) single-metal catalysts, as a paradigmatic example of single-atom versus few-atom catalysts. An inverted mold assumption is proposed to identify the factors determining the number, shape and packing manner of metal atoms inside the pores of gh-C3N4. The area matching between virtual fragments and metal fillers and lattice inheritance from N coordination and metal aggregates allow for a stable Ni-Co/gh-C3N4, which would possess more active sites and a more complex structure-activity relation than single-atom doping. The hydrogen production behavior and catalytic activity of this catalyst are comprehensively discussed. Ni-Co/gh-C3N4 exhibits higher hydrogen evolution activity than Ni1(Co1)/gh-C3N4 at an appropriate H coverage, which is comparable to Pt under analogous conditions. This strategy, derived from the inverted mold assumption, is deemed to be a simple and easy-to-operate method for designing and building metal aggregates confined inside the pores of two-dimensional materials and in the cavities of nanoparticles for few-atom catalysts.

Minimally Invasive Semiconductor Laser Surgery Combined with 5-ALA Photodynamic Therapy for a Chronic Hyperplastic Candidiasis Patient Who Is Ineffective to Antifungal Therapy.

Background: Chronic hyperplastic candidiasis (CHC) is a chronic oral mucosal infection caused by Candida, which has potential for malignant transformation. Diagnosing CHC can be challenging due to its various manifestations. In addition, fungal treatments often prove to be ineffective, highlighting the urgent need for a new safe and efficient treatment approach. Given the potential of CHC to transform into malignancy, it is crucial to emphasize dynamic monitoring and follow-up after treatment. Objective: We attempted to investigate the effect of semiconductor laser pretreatment combined with 5-amino-levulinic acid (5-ALA) photodynamic therapy (PDT) for CHC. Methods: We presented the successful treatment of CHC with mild dysplasia in a 30-year-old man using semiconductor laser and 5-ALA PDT after antifungal therapy proved ineffective. Toluidine blue staining, autofluorescence imaging, and DNA image cytometry were combined to dynamically monitor the progress of the disease. Results: We have obtained positive outcomes with the use of laser combined with PDT treatment. The patients experienced only mild adverse reactions after the treatment, and there was no indication of recurrence or malignant transformation during the subsequent follow-up period, as observed through various auxiliary examinations. Conclusions: This case report suggests that semiconductor laser surgery combined with PDT could be a promising treatment option for patients with CHC who do not respond to antifungal therapy. In addition, the use of combined noninvasive examinations might provide a more accurate assessment of malignant transformation in patients with CHC.

Redox-neutral electrochemical decontamination of hypersaline wastewater with high technology readiness level.

Industrial hypersaline wastewaters contain diverse pollutants that harm the environment. Recovering clean water, alkali and acid from these wastewaters can promote circular economy and environmental protection. However, current electrochemical and advanced oxidation processes, which rely on hydroxyl radicals to degrade organic compounds, are inefficient and energy intensive. Here we report a flow-through redox-neutral electrochemical reactor (FRER) that effectively removes organic contaminants from hypersaline wastewaters via the chlorination-dehalogenation-hydroxylation route involving radical-radical cross-coupling. Bench-scale experiments demonstrate that the FRER achieves over 75% removal of total organic carbon across various compounds, and it maintains decontamination performance for over 360 h and continuously treats real hypersaline wastewaters for two months without corrosion. Integrating the FRER with electrodialysis reduces operating costs by 63.3% and CO2 emissions by 82.6% when compared with traditional multi-effect evaporation-crystallization techniques, placing our system at technology readiness levels of 7-8. The desalinated water, high-purity NaOH (>95%) and acid produced offset industrial production activities and thus support global sustainable development objectives.

Polymer-enhanced peroxidase activity of ceria nanozyme for highly sensitive detection of alkaline phosphatase.

Nanoceria have demonstrated a wide array of catalytic activity similar to natural enzymes, holding considerable significance in the colorimetric detection of alkaline phosphatase (ALP), which is a biomarker of various biological disorders. However, the issues of physiological stability and formation of protein corona, which are strongly related to their surface chemistry, limit their practical application. In this work, CeO2 nanoparticles characterized by enhanced dimensional uniformity and specific surface area were synthesized, followed by encapsulation with various polymers to further increase catalytic activity and physiological stability. Notably, the CeO2 nanoparticles encapsulated within each polymer exhibited improved catalytic characteristics, with PAA-capped CeO2 exhibiting the highest performance. We further demonstrated that the PAA-CeO2 obtained with enhanced catalytic activity was attributed to an increase in surface negative charge. PAA-CeO2 enabled the quantitative assessment of AA activity within a wide concentration range of 10 to 60 µM, with a detection limit of 0.111 µM. Similarly, it allowed for the evaluation of alkaline phosphatase activity throughout a broad range of 10 to 80 U/L, with a detection limit of 0.12 U/L. These detection limits provided adequate sensitivity for the practical detection of ALP in human serum.

Transcatheter arterial perfusion chemotherapy combined with lipiodol chemoembolization for advanced colorectal cancer complicated by obstruction.

Background: Obstruction is a common complication of advanced colorectal cancer. This study was aimed at investigating the safety, efficacy, and feasibility of transcatheter arterial perfusion chemotherapy combined with lipiodol chemoembolization for treating advanced colorectal cancer complicated by obstruction. Patients and methods: This retrospective analysis was conducted using clinical data of patients with advanced colorectal cancer who received arterial infusion chemotherapy combined with lipiodol chemoembolization treatment at our center. Treatment efficacy was evaluated in terms of obstruction-free survival and overall survival, and treatment complications were monitored. Results: Fifty-four patients with colorectal cancer complicated by obstruction were included. All patients successfully underwent transcatheter arterial infusion combined with lipiodol chemoembolization treatment. The average lipiodol dose administered was 2.62 ± 1.45 ml (0.5-5.5 ml). No serious complications such as perforation or tumor dissemination occurred. The clinical success rate was 83.3% (45/54). One month after treatment, the objective response rate (ORR) and disease control rate (DCR) were 66.67% and 88.9%, respectively. The median obstruction-free survival was 5.0 months. No serious adverse events occurred. As of the last follow-up, 6 patients survived, 44 died, and 4 were lost to follow-up. Conclusion: Our findings revealed that transcatheter arterial infusion chemotherapy combined with lipiodol chemoembolization is safe and effective for treating advanced colorectal cancer complicated by obstruction. It may serve as a new treatment strategy for patients with advanced colorectal cancer complicated by obstruction.

Greenspace and human microbiota: A systematic review.

BACKGROUND: Potential effect of greenspace exposure on human microbiota have been explored by a number of observational and interventional studies, but the results remained mixed. We comprehensively synthesized these studies by performing a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: Comprehensive literature searches in three international databases (PubMed, Embase, and Web of Science) and three Chinese databases (China National Knowledge Infrastructure, Wanfang, and China Biology Medicine disc) were conducted from inception to November 1, 2023. Observational and interventional studies that evaluated associations between greenspace exposure and human microbiota at different anatomical sites were included. Studies were assessed using the National Toxicology Program's office of Health Assessment and Translation risk of bias tool and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. Two authors independently performed study selection, data extraction, and risk of bias assessment, and evidence grading. Study results were synthesized descriptively. RESULTS: Twenty studies, including 11 observational studies and 9 interventional studies, were finally included into the systematic review. The microbiota of the included studies was from gut (n = 13), skin (n = 10), oral cavity (n = 5), nasal cavity (n = 5) and eyes (n = 1). The majority of studies reported the associations of greenspace exposure with increased diversity (e.g., richness and Shannon index) and/or altered overall composition of human gut (n = 12) and skin microbiota (n = 8), with increases in the relative abundance of probiotics (e.g., Ruminococcaceae) and decreases in the relative abundance of pathogens (e.g., Streptococcus and Escherichia/Shigella). Due to limited number of studies, evidence concerning greenspace and oral, nasal, and ocular microbiota were still inconclusive. CONCLUSION: The current evidence suggests that greenspace exposure may diversify gut and skin microbiota and alter their composition to healthier profiles. These findings would be helpful in uncovering the potential mechanisms underlying greenspace and human health and in promoting a healthier profile of human microbiota.

Self-distillation framework for document-level relation extraction in low-resource environments.

The objective of document-level relation extraction is to retrieve the relations existing between entities within a document. Currently, deep learning methods have demonstrated superior performance in document-level relation extraction tasks. However, to enhance the model's performance, various methods directly introduce additional modules into the backbone model, which often increases the number of parameters in the overall model. Consequently, deploying these deep models in resource-limited environments presents a challenge. In this article, we introduce a self-distillation framework for document-level relational extraction. We partition the document-level relation extraction model into two distinct modules, namely, the entity embedding representation module and the entity pair embedding representation module. Subsequently, we apply separate distillation techniques to each module to reduce the model's size. In order to evaluate the proposed framework's performance, two benchmark datasets for document-level relation extraction, namely GDA and DocRED are used in this study. The results demonstrate that our model effectively enhances performance and significantly reduces the model's size.

Plant-ant interactions mediate herbivore-induced conspecific negative density dependence in a subtropical forest.

The early growth stage of plants is vital to community diversity and community regeneration. The Janzen-Connell hypothesis predicts that conspecific density dependence lowers the survival of conspecific seedlings by attracting specialist natural enemies, promoting the recruitment and performance of heterospecific neighbors. Recent work has underscored how this conspecific negative density dependence may be mediated by mutualists - such as how mycorrhizal fungi may mediate the accrual of host-specific pathogens beneath the crown of conspecific adult trees. Aboveground mutualist and enemy interactions exist as well, however, and may provide useful insight into density dependence that are as of yet unexplored. Using a long-term seedling demographic dataset in a subtropical forest plot in central China, we confirmed that conspecific neighborhoods had a significant negative effect on seedling survival in this subtropical forest. Furthermore, although we detected more leaf damage in species that were closely related to ants, we found that the presence of ants had significant positive effects on seedling survival. Beside this, we also found a negative effect of ant appearance on seedling growth which may reflect a trade-off between survival and growth. Overall, our findings suggested that ants and conspecific neighborhoods played important but inverse roles on seedling survival and growth. Our results suggest ants may mediate the influence of conspecific negative density dependence on seedling survival at community level.

The Pivotal Function of SLC16A1 and SLC16A1-AS1 in Cancer Progress: Molecular Pathogenesis and Prognosis.

More than 300 membranes make up the SLC family of transporters, utilizing an ion gradient or electrochemical potential difference to move their substrates across biological membranes. The SLC16 gene family contains fourteen members. Proton-linked transportation of monocarboxylates can be promoted by the transporters MCT1, which the SLC16A1 gene family encodes. Glycolysis is constitutively up-regulated in cancer cells, and the amount of lactate produced as a result is correlated with prognosis. Further speaking, SLC16A1 plays an essential role in controlling the growth and spread of tumors, according to mounting evidence. Additionally, LncRNAs are the collective term for all genes that produce RNA transcripts longer than 200 nucleotides but do not convert into proteins. It has steadily developed into a hub for research, offering an innovative approach to tumor study as technology related to molecular biology advances. The growing study has uncovered SLC16A1-AS1, an RNA that acts as an antisense to SLC16A1, which is erroneously expressed in various types of cancers. Therefore, we compiled the most recent information on the physiological functions and underlying processes of SLC16A1 and the LncRNA SLC16A1-AS1 during tumor development to explore their impact on cancer treatment and prognosis. We compiled the most recent information on the physiological functions and underlying processes of SLC16A1 and the LncRNA SLC16A1-AS1 during tumor development to explore their impact on cancer treatment and prognosis. Relevant studies were retrieved and collected through the PubMed system. After determining SLC16A1 and SLC16A1-AS1 as the research object, we found a close relationship between SLC16A1 and tumorigenesis as well as the influencing factors through the analysis of the research articles. SLC16A1 regulates lactate chemotaxis while uncovering SLC16A1- as1 as an antisense RNA acting through multiple pathways; they affect the metabolism of tumor cells and have an impact on the prognosis of patients with various cancers.

γδ T cells in oral diseases.

OBJECTIVE: γδ T cells are a distinct subset of unconventional T cells, which link innate and adaptive immunity by secreting cytokines and interacting with other immune cells, thereby modulating immune responses. As the first line of host defense, γδ T cells are essential for mucosal homeostasis and immune surveillance. When abnormally activated or impaired, γδ T cells can contribute to pathogenic processes. Accumulating evidence has revealed substantial impacts of γδ T cells on the pathogenesis of cancers, infections, and immune-inflammatory diseases. γδ T cells exhibit dual roles in cancers, promoting or inhibiting tumor growth, depending on their phenotypes and the clinical stage of cancers. During infections, γδ T cells exert high cytotoxic activity in infectious diseases, which is essential for combating bacterial and viral infections by recognizing foreign antigens and activating other immune cells. γδ T cells are also implicated in the onset and progression of immune-inflammatory diseases. However, the specific involvement and underlying mechanisms of γδ T cells in oral diseases have not been systematically discussed. METHODS: We conducted a systematic literature review using the PubMed/MEDLINE databases to identify and analyze relevant literature on the roles of γδ T cells in oral diseases. RESULTS: The literature review revealed that γδ T cells play a pivotal role in maintaining oral mucosal homeostasis and are involved in the pathogenesis of oral cancers, periodontal diseases, graft-versus-host disease (GVHD), oral lichen planus (OLP), and oral candidiasis. γδ T cells mainly influence various pathophysiological processes, such as anti-tumor activity, eradication of infection, and immune response regulation. CONCLUSION: This review focuses on the involvement of γδ T cells in oral diseases, with a particular emphasis on the main functions and underlying mechanisms by which γδ T cells influence the pathogenesis and progression of these conditions. This review underscores the potential of γδ T cells as therapeutic targets in managing oral health issues.

Structural Reversibility of Nanoscaled Sn Anodes.

Alloying-type anode materials provide high capacity for lithium-ion batteries; however, they suffer pulverization problems resulting from the volume change during cycling. Realizing the cycling reversibility of these anodes is therefore critical for sustaining their electrochemical performance. Here, we investigate the structural reversibility of Sn NPs during cycling at atomic-level resolution utilizing in situ high-resolution TEM. We observed a surprisingly near-perfect structural reversibility after a complete cycle. A three-step phase transition happens during lithiation, accompanied by the generation of a significant number of defects, grain boundaries, and up to 202% volume expansion. In subsequent delithiation, the volume, morphology, and crystallinity of the Sn NPs were restored to their initial state. Theoretical calculations show that compressive stress drives the removal of vacancies generated within the NPs during delithiation, therefore maintaining their intact morphology. This work demonstrates that removing vacancies during cycling can efficiently improve the structural reversibility of high-capacity anode materials.

Comparative discriminant analysis of Mesua ferrea L. and its adulterants.

The Uygur medicinal material Mesua ferrea L. has different plant sources in the market. The flower bud of Mammea siamensis T. Anders, which originated from Myanmar and Thailand, is actually used in the dosage room of Uygur hospitals and pharmaceutical enterprises in Xinjiang Region. On the contrary, flowers of Mesua ferrea L. are less frequently used. In this study, the taxonomic characteristics, liquid chromatography-mass spectrometry (LC/MS) and liquid chromatography (HPLC) were used to compare the similarities and differences between the two species. The results showed that the flowers of the two plants were significantly different in morphology, but the similarity of chemical components was high. At the same time, the study also found that Mesua ferrea L. and Mammea siamensis T. Anders contain a large amount of vitexin and isovitexin, which can be used for qualitative and quantitative research. This study provides a reference for the identification, development and utilization of Mesua ferrea L medicinal materials and the revision of quality standards.

The Indispensable Roles of GMDS and GMDS-AS1 in the Advancement of Cancer: Fucosylation, Signal Pathway and Molecular Pathogenesis.

Fucosylation is facilitated by converting GDP-mannose to GDP-4-keto-6-deoxymannose, which GDP-mannose 4,6-dehydratase, a crucial enzyme in the route, carries out. One of the most prevalent glycosylation alterations linked to cancer has reportedly been identified as fucosylation. There is mounting evidence that GMDS is intimately linked to the onset and spread of cancer. Furthermore, the significance of long-chain non-coding RNAs in the development and metastasis of cancer is becoming more well-recognized, and the regulatory mechanism of lncRNAs has emerged as a prominent area of study in the biological sciences. GMDS-AS1, an antisense RNA of GMDS, was discovered to have the potential to be an oncogene. We have acquired and analyzed relevant data to understand better how GMDS-AS1 and its lncRNA work physiologically and in tumorigenesis and progression. Additionally, we have looked into the possible effects of these molecules on cancer treatment approaches and patient outcomes. The physiological roles and putative processes of GMDS and lncRNA GMDS-AS1 throughout the development and progression of tumors have been assembled and examined. We also examined how these chemicals might affect patient prognosis and cancer therapy approaches. GMDS and GMDS-AS1 were determined to be research subjects by searching and gathering pertinent studies using the PubMed system. The analysis of these research articles demonstrated the close relationship between GMDS and GMDS-AS1 and tumorigenesis and the factors that influence them. GMDS plays a vital role in regulating fucosylation. The related antisense gene GMDS-AS1 affects the biological behaviors of cancer cells through multiple pathways, including the key processes of proliferation, migration, invasion, and apoptosis, providing potential biomarkers and therapeutic targets for cancer treatment and prognosis assessment.

Autosis: a new form of cell death in myocardial ischemia-reperfusion injury.

Cardiomyocytes undergo a variety of cell death events during myocardial ischemia‒reperfusion injury (MIRI). Understanding the causes of cardiomyocyte mortality is critical for the prevention and treatment of MIRI. Among the various types of cell death, autosis is a recently identified type of autophagic cell death with distinct morphological and chemical characteristics. Autosis can be attenuated by autophagy inhibitors but not reversed by apoptosis or necrosis inhibitors. In recent years, it has been shown that during the late phase of reperfusion, autosis is activated, which exacerbates myocardial injury. This article describes the characteristics of autosis, autophagic cell death, and the relationship between autophagic cell death and autosis; reviews the mechanism of autosis in MIRI; and discusses its clinical significance.

C-H arylation of thiopyran derivatives with aryl halides.

A C-H arylation of thiopyran derivatives with aryl halides has been developed. Under the catalysis of Pd(OAc)2/Ag2CO3, the C-H arylation takes place at the α-position of the thiopyran ring. When dibromo-substituted compounds are used as reactants, double C-H arylations may occur on the same thiopyran ring at its α- and ß-positions.

Charge Carrier Regulation for Efficient Blue Quantum-Dot Light-Emitting Diodes Via a High-Mobility Coplanar Cyclopentane[b]thiopyran Derivative.

The performance of blue quantum dot light-emitting diodes (QLEDs) is limited by unbalanced charge injection, resulting from insufficient holes caused by low mobility or significant energy barriers. Here, we introduce an angular-shaped heteroarene based on cyclopentane[b]thiopyran (C8-SS) to modify the hole transport layer poly-N-vinylcarbazole (PVK), in blue QLEDs. C8-SS exhibits high hole mobility and conductivity due to the π···π and S···π interactions. Introducing C8-SS to PVK significantly enhanced hole mobility, increasing it by 2 orders of magnitude from 2.44 × 10-6 to 1.73 × 10-4 cm2 V-1 s-1. Benefiting from high mobility and conductivity, PVK:C8-SS-based QLEDs exhibit a low turn-on voltage (Von) of 3.2 V. More importantly, the optimized QLEDs achieve a high peak power efficiency (PE) of 7.13 lm/W, which is 2.65 times that of the control QLEDs. The as-proposed interface engineering provides a novel and effective strategy for achieving high-performance blue QLEDs in low-energy consumption lighting applications.

Implications of innate lymphoid cells in oral diseases.

Innate lymphoid cells (ILCs), as newly discovered antigen-independent innate immune cells, respond promptly to stimuli by secreting effector cytokines to exert effector functions similar to those of T cells. ILCs predominantly reside at mucosal sites and play critical roles in defending against infections, maintaining mucosal homeostasis, regulating inflammatory and immune responses, and participating in tumorigenesis. Recently, there has been a growing interest in the role of ILCs in oral diseases. This review outlines the classifications and the major characteristics of ILCs, and then comprehensively expatiates the research on ILCs in oral cancer, primary Sjogren's syndrome, periodontal diseases, oral lichen planus, oral candidiasis, Behcet's disease, and pemphigus vulgaris, aiming at summarising the implications of ILCs in oral diseases and providing new ideas for further research.

Thiopyran-Fused Mono and Double Helicenes with Low Band Gaps via Simultaneous Ring Expansion and 6-endo Cyclizations.

Mono and double helicenes (M5, M6, D5, and D6) containing six-membered thiopyran rings have been successfully prepared via simultaneous ring expansion and 6-endo cycloisomerizations from the corresponding precursors with five-membered thiophene rings. Although D5 and D6 exhibit similar chemical structures, they demonstrate completely different helical structures because of their distinct steric clashes caused by the incorporated methyl groups. Moreover, all of the thiopyran-fused helicenes exhibit broad absorption bands covering the visible and near-infrared regions.

Melatonin improves salivary gland damage and hypofunction in pSS by inhibiting IL-6/STAT3 signaling through its receptor-dependent manner.

OBJECTIVE: Primary Sjogren's syndrome (pSS) is an autoimmune disease of the exocrine glands with no specific or efficient treatments. Melatonin, a natural hormone, is revealed to show multiple biological functions, both receptor-dependent and independent effects, including anti-apoptotic, antioxidant, and anti-inflammatory activities. However, the potential mechanism by which melatonin protects salivary glands (SGs) of pSS from damage needs to be clarified. The purpose of current study was to explore the role and receptor-related mechanisms of melatonin in pSS-induced glandular damage. METHODS AND RESULTS: NOD/Ltj mice were used to spontaneously mimic pSS-induced glandular hypofunction in vivo and primary human salivary gland epithelial (HSGE) cells were stimulated by interferon-γ (IFN-γ) to mimic pSS-induced inflammation in SGs cells in vitro. Melatonin-treated mice exhibited a significant reduction in SG injury of NOD/Ltj mice, which was accompanied by an increase in salivary flow rate, a decrease in inflammatory infiltration within the gland, and a suppression of oxidative stress indicators as well as cell apoptosis. Notably, both melatonin membrane receptors and nuclear receptors played an important role in the anti-apoptotic effects of melatonin on the SGs of NOD/Ltj mice. Furthermore, melatonin blocked the IL-6/STAT3 pathway through receptor-dependent manners in IFN-γ-stimulated HSGE cells. However, it was evident that the anti-oxidative and anti-apoptotic properties of melatonin on IFN-γ-stimulated HSGE cells were diminished by IL-6 treatment. CONCLUSION: Melatonin had the potential to mitigate inflammation, oxidative stress, and apoptosis in SGs of pSS by inhibiting the IL-6/STAT3 pathway through receptor-dependent mechanisms. This intervention effectively prevented glandular damage and preserved functional integrity.