Histopathological staging of atrophic lesions of gastric mucosa.

Objective: To study the histopathological staging of atrophic lesions of the gastric mucosa. Methods: Histology and immunohistochemistry were used to closely examine 2144 specimens of atrophic gastric mucosa that were taken from endoscopic biopsies. Results: When the gastric mucosa epithelium is affected by infection, chemical stimulation, immune factors, genetic factors, and other factors, it may cause an atrophy of gastric mucosa epithelium and a decrease in the number of glands, intestinal metaplasia, hyperplasia of smooth muscle fibers, and atrophy of stem cells in the proliferative zone. In this study, we characterized the above lesions as atrophic lesions of the gastric mucosa. Based on the morphological and histological characteristics of the lesion, as well as the law of cell proliferation and transformation during its occurrence and development, we propose five stages. We also noted the onset age, gender correlation, and histopathological characteristics of each stage of gastric mucosal atrophies. Conclusion: Understanding the pathological staging of gastric mucosal atrophy is essential for treating patients correctly and keeping track of changes in malignant cells. It is also very important in preventing the initiation of gastric cancer or from getting worse.

Deciphering the role of wound healing genes in skin cutaneous melanoma: Insights into expression, methylation, mutations, and therapeutic implications.

Skin Cutaneous Melanoma (SKCM) is a form of cancer that originates in the pigment-producing cells, known as melanocytes, of the skin. Delay wound healing is often correlated with the occurrence of and progression of SKCM. In this comprehensive study, we investigated the intricate roles of two important wound healing genes in SKCM, including Matrix Metalloproteinase-2 (MMP2) and Matrix Metalloproteinase-9 (MMP9). Through a multi-faceted approach, we collected clinical samples, conducted molecular experiments, including RT-qPCR, bisulphite sequencing, cell culture, cell Counting Kit-8, colony formation, and wound healing assays. Beside this, we also used various other databases/tools/approaches for additional analysis including, UALCAN, GEPIA, HPA, MEXPRESS, cBioPortal, KM plotter, DrugBank, and molecular docking. Our results revealed a significant up-regulation of MMP2 and MMP9 in SKCM tissues compared to normal counterparts. Moreover, promoter methylation analysis suggested an epigenetic regulatory mechanism. Validations using TCGA datasets and immunohistochemistry emphasized the clinical relevance of MMP2 and MMP9 dysregulation. Functional assays demonstrated their synergistic impact on proliferation and migration in SKCM cells. Furthermore, we identified potential therapeutic candidates, Estradiol and Calcitriol, through drug prediction and molecular docking analyses. These compounds exhibited binding affinities, suggesting their potential as MMP2/MMP9 inhibitors. Overall, our study elucidates the diagnostic, prognostic, and therapeutic implications of MMP2 and MMP9 in SKCM, shedding light on their complex interplay in SKCM occurrence and progression.

Current developments and future perspectives of nanotechnology in orthopedic implants: an updated review.

Orthopedic implants are the most commonly used fracture fixation devices for facilitating the growth and development of incipient bone and treating bone diseases and defects. However, most orthopedic implants suffer from various drawbacks and complications, including bacterial adhesion, poor cell proliferation, and limited resistance to corrosion. One of the major drawbacks of currently available orthopedic implants is their inadequate osseointegration at the tissue-implant interface. This leads to loosening as a result of immunological rejection, wear debris formation, low mechanical fixation, and implant-related infections. Nanotechnology holds the promise to offer a wide range of innovative technologies for use in translational orthopedic research. Nanomaterials have great potential for use in orthopedic applications due to their exceptional tribological qualities, high resistance to wear and tear, ability to maintain drug release, capacity for osseointegration, and capability to regenerate tissue. Furthermore, nanostructured materials possess the ability to mimic the features and hierarchical structure of native bones. They facilitate cell proliferation, decrease the rate of infection, and prevent biofilm formation, among other diverse functions. The emergence of nanostructured polymers, metals, ceramics, and carbon materials has enabled novel approaches in orthopaedic research. This review provides a concise overview of nanotechnology-based biomaterials utilized in orthopedics, encompassing metallic and nonmetallic nanomaterials. A further overview is provided regarding the biomedical applications of nanotechnology-based biomaterials, including their application in orthopedics for drug delivery systems and bone tissue engineering to facilitate scaffold preparation, surface modification of implantable materials to improve their osteointegration properties, and treatment of musculoskeletal infections. Hence, this review article offers a contemporary overview of the current applications of nanotechnology in orthopedic implants and bone tissue engineering, as well as its prospective future applications.

Chronic infectious unilateral giant thyroid cyst related to diabetes mellitus: A case report.

BACKGROUND: Patients rarely develop complicated infections in thyroid cysts. Here, we describe a patient with chronic infected unilateral giant thyroid cyst related to diabetes mellitus (DM). CASE SUMMARY: A 66-year-old male was admitted due to an evident neck lump for 5 d after approximately 40 years of gradually progressive neck mass and 7 years of DM. Doppler ultrasound and computed tomography scan showed a giant lump in the left thyroid gland lobe. He was diagnosed with a large thyroid nodule complicated by tracheal dislocation and had surgical indications. Surgical exploration revealed evident inflammatory edema and exudation between the left anterior neck muscles, the nodule and glandular tissue. Fortunately, inflammatory lesions did not affect major neck vessels. Finally, a left partial thyroidectomy was performed. Macroscopic observation showed that the cystic thyroid mass consisted of extensive cystic wall calcification and was rich in massive rough sand-like calculi content and purulent matter. Postoperative pathology confirmed benign thyroid cyst with chronic infection. CONCLUSION: The progression of this chronic infectious unilateral giant thyroid cyst may have been related to DM, and identifying blood vessels involvement can prevent serious complications during operation.

Enhancing antibacterial properties of titanium implants through a novel Ag-TiO2-OTS nanocomposite coating: a comprehensive study on resist-killing-disintegrate approach.

Titanium (Ti) implants are widely used in orthopedic and dental applications due to their excellent biocompatibility and mechanical properties. However, bacterial adhesion and subsequent biofilm formation on implant surfaces pose a significant risk of postoperative infections and complications. Conventional surface modifications often lack long-lasting antibacterial efficacy, necessitating the development of novel coatings with enhanced antimicrobial properties. This study aims to develop a novel Ag-TiO2-OTS (Silver-Titanium dioxide-Octadecyltrichlorosilane, ATO) nanocomposite coating, through a chemical plating method. By employing a 'resist-killing-disintegrate' approach, the coating is designed to inhibit bacterial adhesion effectively, and facilitate pollutant removal with lasting effects. Characterization of the coatings was performed using spectroscopy, electron microscopy, and contact angle analysis. Antibacterial efficacy, quantitatively evaluated against E. coli and S. aureus over 168 h, showed a significant reduction in bacterial adhesion by 76.6% and 66.5% respectively, and bacterial removal rates were up to 83.8% and 73.3% in comparison to uncoated Ti-base material. Additionally, antibacterial assays indicated that the ratio of the Lifshitz-van der Waals apolar component to electron donor surface energy components significantly influences bacterial adhesion and removal, underscoring a tunable parameter for optimizing antibacterial surfaces. Biocompatibility assessments with the L929 cell line revealed that the ATO coatings exhibited excellent biocompatibility, with minimal cytotoxicity and no significant impact on cell proliferation or apoptosis. The ATO coatings provided a multi-functionality surface that not only resists bacterial colonization but also possesses self-cleaning capabilities, thereby marking a substantial advancement in the development of antibacterial coatings for medical implants.

A novel membrane-free electrochemical separation-filtering crystallization coupling process for treating circulating cooling water.

The traditional electrochemical descaling process exhibits drawbacks, including low OH- utilization efficiency, constrained cathode deposition area, and protracted homogeneous precipitation time. Consequently, this study introduces a novel membrane-free electrochemical separation-filtering crystallization (MFES-FC) coupling process to treat circulating cooling water (CCW). In the membrane-free electrochemical separation (MFES) system, OH- is rapidly extracted by pump suction from the porous cathode boundary layer solution, preventing neutralization with H+, thereby enhancing the removal of Ca2+ and Mg2+. Experimental results indicate that the pH of the pump suction water can swiftly increase from 8.13 to 11.42 within 10 min. Owing to the high supersaturation of the pump suction water, this study couples the MFES with a filtration crystallization (FC) system that employs activated carbon as the medium. This approach captures scale particles to enhance water quality and expedites the homogeneous precipitation of hardness ions, shortening the treatment time while further augmenting the removal rate. After the MFES-FC treatment, the single-pass removal rates for total hardness, Ca2+ hardness, Mg2+ hardness, and alkalinity in the effluent reached 92 %, 97 %, 64 %, and 67 %, respectively, with turbidity of 3 NTU, current efficiency of 86.6 %, and energy consumption of 7.19 kWh·kg-1 CaCO3. This coupling process facilitates an effective removal of hardness and alkalinity at a comparatively low cost, offering a new reference and inspiration for advancements in electrochemical descaling technology.

MV-SHIF: Multi-view symmetric hypothesis inference fusion network for emotion-cause pair extraction in documents.

Emotion-cause pair extraction (ECPE) is a challenging task that aims to automatically identify pairs of emotions and their causes from documents. The difficulty of ECPE lies in distinguishing valid emotion-cause pairs from many irrelevant ones. Most previous methods have primarily focused on utilizing multi-task learning to extract semantic information solely from documents without explicitly encoding the relations between clauses. We propose a new approach that incorporates textual entailment paradigm aiming to infer the entailment relationship between the original document as the premise and the clauses or pairs described as the hypothesis. Our approach designs label-view hypothesis templates to improve ECPE by filtering out irrelevant emotion and cause clauses. Furthermore, we formulate candidate emotion-cause pairs as hypothesis statements, and define explicit multi-view symmetric templates to capture the emotion-cause relation semantics. The text entailment recognition for ECPE is finally implemented by fusing multi-view semantic information using a simplified capsule network. Our proposed model achieves state-of-the-art performance on ECPE compared to previous baselines. More importantly, this work demonstrates a novel effective way of applying the textual entailment paradigm to ECPE or clause-level causal discovery by designing multi-view hypothesis inference and information fusion.

Pharmacokinetics, pharmacodynamics, and safety of frunexian in healthy Chinese volunteer adults: A randomized dose-escalation phase I study.

The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of frunexian (formerly known as EP-7041 and HSK36273) injection, a small molecule inhibitor of activated coagulation factor XI (FXIa), in healthy Chinese adult volunteers. This study was a randomized, placebo- and positive-controlled, sequential, ascending-dose (0.3/0.6/1.0/1.5/2.25 mg/kg/h) study of 5-day continuous intravenous infusions of frunexian. Frunexian administration exhibited an acceptable safety profile with no bleeding events. Steady state was rapidly reached with a median time ranging from 1.02 to 1.50 h. The mean half-life ranged from 1.15 to 1.43 h. Frunexian plasma concentration at a steady state and area under the concentration-time curve exhibited dose-proportional increases. The dose-escalation study of frunexian demonstrated its progressively enhanced capacities to prolong activated partial thromboplastin time (aPTT) and inhibit FXIa activity. The correlations between PK and PD biomarkers (aPTT/baseline and FXI clotting activity/baseline) were described by the two Emax models, with the EC50 values of 8940 and 1300 ng/mL, respectively. Frunexian exhibits good safety and PK/PD properties, suggesting it is a promising candidate for anticoagulant drug.

Learning Graph Attentions via Replicator Dynamics.

Graph Attention (GA) which aims to learn the attention coefficients for graph edges has achieved impressive performance in GNNs on many graph learning tasks. However, existing GAs are usually learned based on edges' (or connected nodes') features which fail to fully capture the rich structural information of edges. Some recent research attempts to incorporate the structural information into GA learning but how to fully exploit them in GA learning is still a challenging problem. To address this challenge, in this work, we propose to leverage a new Replicator Dynamics model for graph attention learning, termed Graph Replicator Attention (GRA). The core of GRA is our derivation of replicator dynamics based sparse attention diffusion which can explicitly learn context-aware and sparse preserved graph attentions via a simple self-supervised way. Moreover, GRA can be theoretically explained from an energy minimization model. This provides a more theoretical justification for the proposed GRA method. Experiments on several graph learning tasks demonstrate the effectiveness and advantages of the proposed GRA method on ten benchmark datasets.

A cross-sectional study on the potential drug-drug interaction risk of COVID-19 patients in hospital.

OBJECTIVE: To investigate the incidence of and risk factors for potential drug-drug interactions (DDIs) among elderly patients with corona virus disease 2019 (-COVID-19) in hospital and to explore management strategies to reduce the occurrence of potential DDIs and ensure patient medication safety. MATERIALS AND METHODS: This was a descriptive, retrospective cross-sectional study among patients aged 65 years and older who were hospitalized with COVID-19. Potential DDIs associated with prescriptions containing two or more medicines were analyzed with Lexicomp software, the incidence of DDIs was calculated, recommendations for medication adjustment were formulated, and the χ2-test and binary logistic regression were used to analyze related risk factors. RESULTS: A total of 772 prescriptions were analyzed, 527 (68.26) of which involved 5,732 potential DDIs. The results of this study showed that a total of 152 (28.84%) prescriptions had 270 X risk class potential DDIs (i.e., avoid combining), 313 (59.39%) prescriptions had 1,161 D risk class potential DDIs (i.e., consider therapy modification), and 476 (90.32%) prescriptions had 4,301 C risk class potential DDIs (i.e., monitor therapy). The study findings showed that the total number of drugs (p < 0.001), the length of hospital stay (p < 0.001), and the number of comorbidities (p < 0.001) were risk factors affecting the occurrence of potential DDIs. CONCLUSION: This study identified factors associated with potential DDIs, which can assist in changing medication strategies, preventing adverse drug reactions, and improving clinical efficacy.

CPA4 as a biomarker promotes the proliferation, migration and metastasis of clear cell renal cell carcinoma cells.

Clear cell renal cell carcinoma (ccRCC) is a commonly occurring and highly aggressive urological malignancy characterized by a significant mortality rate. Current therapeutic options for advanced ccRCC are limited, necessitating the discovery of novel biomarkers and therapeutic targets. Carboxypeptidase A4 (CPA4) is a zinc-containing metallocarboxypeptidase with implications in various cancer types, but its role in ccRCC remains unexplored. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized in order to investigate the differential expression patterns of CPA4. The expression of CPA4 in ccRCC patients was further verified using immunohistochemical (IHC) examination of 24 clinical specimens. A network of protein-protein interactions (PPI) was established, incorporating CPA4 and its genes that were expressed differentially. Functional enrichment analyses were conducted to anticipate the contribution of CPA4 in the development of ccRCC. To validate our earlier study, we conducted real-time PCR and cell functional tests on ccRCC cell lines. Our findings revealed that CPA4 is overexpressed in ccRCC, and the higher the expression of CPA4, the worse the clinical outcomes such as TNM stage, pathological stage, histological grade, etc. Moreover, patients with high CPA4 expression had worse overall survival, disease-specific survival and progress-free interval than patients with low expression. The PPI network analysis highlighted potential interactions contributing to ccRCC progression. Functional enrichment analysis indicated the involvement of CPA4 in the regulation of key pathways associated with ccRCC development. Additionally, immune infiltration analysis suggested a potential link between CPA4 expression and immune response in the tumour microenvironment. Finally, cell functional studies in ccRCC cell lines shed light on the molecular mechanisms underlying the role of CPA4 in promoting ccRCC formation. Overall, our study unveils CPA4 as a promising biomarker with prognostic potential in ccRCC. The identified interactions and pathways provide valuable insights into its implications in ccRCC development and offer a foundation for future research on targeted therapies. Further investigation of CPA4's involvement in immune responses may contribute to the development of immunotherapeutic strategies for ccRCC treatment.

Prognostic Evaluation for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Patients Treated with Transarterial Chemoembolization Plus Molecular Targeted Therapies-Development and Validation of the ABPS Score.

RATIONALE AND OBJECTIVES: Transarterial chemoembolization (TACE) plus molecular targeted therapies has emerged as the main approach for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). A robust model for outcome prediction and risk stratification of recommended TACE plus molecular targeted therapies candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. METHODS: A retrospective analysis was conducted on 384 patients with HCC and PVTT who underwent TACE plus molecular targeted therapies at 16 different institutions. We developed and validated a new prognostic score which called ABPS score. Additionally, an external validation was performed on data from 200 patients enrolled in a prospective cohort study. RESULTS: The ABPS score (ranging from 0 to 3 scores), which involves only Albumin-bilirubin (ALBI, grade 1: 0 score; grade 2: 1 score), PVTT(I-II type: 0 score; III-IV type: 1 score), and systemic-immune inflammation index (SII,<550 × 1012: 0 score; ≥550 × 1012: 1 score). Patients were categorized into three risk groups based on their ABPS score: ABPS-A, B, and C (scored 0, 1-2, and 3, respectively). The concordance index (C-index) of the ABPS scoring system was calculated to be 0.802, significantly outperforming the HAP score (0.758), 6-12 (0.712), Up to 7 (0.683), and ALBI (0.595) scoring systems (all P < 0.05). These research findings were further validated in the external validation cohorts. CONCLUSION: The ABPS score demonstrated a strong association with survival outcomes and radiological response in patients undergoing TACE plus molecular targeted therapy for HCC with PVTT. The ABPS scoring system could serve as a valuable tool to guide treatment selection for these patients.

Development and evaluation of a time-resolved fluorescence labelled immunochromatographic strip assay for rapid and quantitative detection of bovine herpesvirus 1.

Bovine herpes virus 1 (BoHV-1) causes a wide variety of diseases in wild and domestic cattle. The most widely used method for viral identification is real-time PCR, which can only be performed in laboratories using sophisticated instruments by expert personnel. Herein, we developed an ultrasensitive time-resolved fluorescence lateral flow immunochromatographic strip (ICS) assay for detecting BoHV-1 in bovine samples using a monoclonal antibody against BoHV-1 labelled with fluorescent microspheres, which can be applied in any setting. The intact process from sample collection to final result can be achieved in 15 min. The limit of detection of the assay for BoHV-1 was 102 TCID50/100 µL. The coincidence rate of the ICS method and real-time PCR recommended by the World Organization for Animal Health (WOAH) was 100% for negative, 92.30% for positive, and 95.42% for total, as evaluated by the detection of 131 clinical samples. This detection method was specifically targeted to BoHV-1, not exhibiting cross-reactivity with other bovine pathogens including BoHV-5. We developed an ICS assay equipped with a portable instrument that offers a sensitive and specific platform for the rapid and reliable detection of BoHV-1 in the field. The Point-of-Care test of BoHV-1 is suitable for the screening and surveillance of BoHV-1 in dairy herds.

Preparation of Asymmetric Al2O3-SiO2 Janus Nanoparticles in Aqueous Phase and Its Interfacial Property.

In this study, asymmetric Al2O3-SiO2 Janus nanoparticles with a dumbbell-like structure were synthesized by a facile chemical process in the aqueous phase. Prior to synthesis, Al2O3 nanoparticles in hydrosol were amino-modified using 3-aminopropyl triethoxysilane (KH550) and then carboxyl acid-functionalized using a ring-opening reaction of the amine functions with succinic anhydride, imparting unique anionic properties to the Al2O3 end. SiO2 nanoparticles were rendered hydrophobic through modification with hexamethyldisilazane (HMDS) and further functionalized with 3-chloropropyl triethoxysilane (KH230). The two nanoparticle hydrosols were then mixed, and the asymmetric Al2O3-SiO2 Janus nanoparticles were synthesized via the reaction between the -NH2 and -CH2Cl groups. The prepared Janus nanoparticles were primarily characterized by dynamic light scattering (DLS), Zeta potential (ZP), and transmission electron microscopy (TEM). The results indicated that about 90% of the modified Al2O3 and SiO2 nanoparticles were covalently coupled in a one-to-one manner to form the dominant dumbbell-like structure. These Janus nanoparticles exhibit amphiphilic properties, making them highly promising surfactants for emulsifying oil-water mixtures.

Photo-modulated activation of organic bases enabling microencapsulation and on-demand reactivity.

A method is developed for facile encapsulation of reactive organic bases with potential application for autonomous damage detection and self-healing polymers. Highly reactive chemicals such as bases and acids are challenging to encapsulate by traditional oil-water emulsion techniques due to unfavorable physical and chemical interactions. In this work, reactivity of the bases is temporarily masked with photo-removable protecting groups, and the resulting inactive payloads are encapsulated via an in situ emulsion-templated interfacial polymerization method. The encapsulated payloads are then activated to restore the organic bases via photo irradiation, either before or after being released from the core-shell carriers. The efficacy of the photo-activated capsules is demonstrated by a damage-triggered, pH-induced color change in polymeric coatings and by recovery of adhesive strength of a damaged interface. Given the wide range of potential photo-deprotection chemistries, this encapsulation scheme provides a simple but powerful method for storage and targeted delivery of a broad variety of reactive chemicals, promoting design of diverse autonomous functionalities in polymeric materials.

Tailored chitosan integration in diatomaceous earth particles as a scaffold for fructosyltransferase immobilization in fructo-oligosaccharide production.

BACKGROUND: Fructo-oligosaccharide (FOS) belongs to the group of short inulin-type fructans and is one of the most important non-digestible bifid-oligosaccharides capable of biotransforming sucrose using fructosyltransferase (FTase). However, there are no immobilized FTase products that can be successfully used industrially. In this study, diatomite was subjected to extrusion, sintering and granulation to form diatomaceous earth particles that were further modified via chitosan aminomethylation for modification. FTase derived from Aspergillus oryzae was successfully immobilized on the modified support via covalent binding. RESULTS: The immobilized enzyme activity was 503 IU g-1 at an enzyme concentration of 0.6 mg mL-1, immobilization pH of 7.0 and contact time of 3 h. Additionally, the immobilization yield was 56.91%. Notably, the immobilized enzyme was more stable under acidic conditions. Moreover, the half-life of the immobilized enzyme was 20.80 and 10.96 times as long as that of the free enzyme at 45 and 60 °C, respectively. The results show good reusability, as evidenced by the 84.77% retention of original enzyme activity after eight cycles. Additionally, the column transit time of the substrate was 35.56 min when the immobilized enzyme was applied in a packed-bed reactor. Furthermore, a consistently high FOS production yield of 60.68% was achieved and maintained over the 15-day monitoring period. CONCLUSIONS: Our results suggest that immobilized FTase is a viable candidate for continuous FOS production on an industrial scale. © 2024 Society of Chemical Industry.

DNAJA1­knockout alleviates heat stroke­induced endothelial barrier disruption via improving thermal tolerance and suppressing the MLCK­MLC signaling pathway.

Endothelial barrier disruption plays a key role in the pathophysiology of heat stroke (HS). Knockout of DNAJA1 (DNAJA1­KO) is thought to be protective against HS based on a genome­wide CRISPR­Cas9 screen experiment. The present study aimed to illustrate the function of DNAJA1­KO against HS in human umbilical vein endothelial cells. DNAJA1­KO cells were infected using a lentivirus to investigate the role of DNAJA1­KO in HS­induced endothelial barrier disruption. It was shown that DNAJA1­KO could ameliorate decreased cell viability and increased cell injury, according to the results of Cell Counting Kit­8 and lactate dehydrogenase assays. Moreover, HS­induced endothelial cell apoptosis was inhibited by DNAJA1­KO, as indicated by Annexin V­FITC/PI staining and cleaved­caspase­3 expression using flow cytometry and western blotting, respectively. Furthermore, the endothelial barrier function, as measured by transepithelial electrical resistance and FITC­Dextran, was sustained during HS. DNAJA1­KO was not found to have a significant effect on the expression and distribution of cell junction proteins under normal conditions without HS. However, DNAJA1­KO could effectively protect the HS­induced decrease in the expression and distribution of cell junction proteins, including zonula occludens­1, claudin­5, junctional adhesion molecule A and occludin. A total of 4,394 proteins were identified using proteomic analysis, of which 102 differentially expressed proteins (DEPs) were activated in HS­induced wild­type cells and inhibited by DNAJA1­KO. DEPs were investigated by enrichment analysis, which demonstrated significant enrichment in the 'calcium signaling pathway' and associations with vascular­barrier regulation. Furthermore, the 'myosin light­chain kinase (MLCK)­MLC signaling pathway' was proven to be activated by HS and inhibited by DNAJA1­KO, as expected. Moreover, DNAJA1­KO mice and a HS mouse model were established to demonstrate the protective effects on endothelial barrier in vivo. In conclusion, the results of the present study suggested that DNAJA1­KO alleviates HS­induced endothelial barrier disruption by improving thermal tolerance and suppressing the MLCK­MLC signaling pathway.

A New Modulator of Neuroinflammation in Diabetic Retinopathy: USP25.

Diabetic retinopathy (DR) is a diabetes-associated complication that poses a threat to vision, distinguished by persistent and mild inflammation of the retinal microvasculature. The activation of microglia plays a crucial role in driving this pathological progression. Previous investigations have demonstrated that ubiquitin-specific peptidase 25 (USP25), a deubiquitinating enzyme, is involved in the regulation of immune cell activity. Nevertheless, the precise mechanisms through which USP25 contributes to the development of DR remain incompletely elucidated. Firstly, we have demonstrated the potential mechanism by which ROCKs can facilitate microglial activation and augment the synthesis of inflammatory mediators through the modulation of NF-κB signaling pathways in a high-glucose milieu. Furthermore, our study has provided novel insights by demonstrating that the regulatory role of USP25 in the secretion of proinflammatory factors is mediated through the involvement of ROCK in modulating the expression of NF-κB and facilitating the nuclear translocation of the phosphatase NF-κB. This regulatory mechanism plays a crucial role in modulating the activation of microglial cells within a high-glycemic environment. Hence, USP25 emerges as a pivotal determinant for the inflammatory activation of microglial cells, and its inhibition exhibits a dual effect of promoting retinal neuron survival while suppressing the inflammatory response in the retina. In conclusion, the promotion of diabetic retinopathy (DR) progression by USP25 is attributed to its facilitation of microglial activation induced by high glucose levels, a process mediated by the ROCK pathway. These findings highlight the importance of considering USP25 as a potential therapeutic target for the management of diabetic neuroinflammation.