NSUN5/TET2-directed chromatin-associated RNA modification of 5-methylcytosine to 5-hydroxymethylcytosine governs glioma immune evasion.

Malignant glioma exhibits immune evasion characterized by highly expressing the immune checkpoint CD47. RNA 5-methylcytosine(m5C) modification plays a pivotal role in tumor pathogenesis. However, the mechanism underlying m5C-modified RNA metabolism remains unclear, as does the contribution of m5C-modified RNA to the glioma immune microenvironment. In this study, we demonstrate that the canonical 28SrRNA methyltransferase NSUN5 down-regulates ß-catenin by promoting the degradation of its mRNA, leading to enhanced phagocytosis of tumor-associated macrophages (TAMs). Specifically, the NSUN5-induced suppression of ß-catenin relies on its methyltransferase activity mediated by cysteine 359 (C359) and is not influenced by its localization in the nucleolus. Intriguingly, NSUN5 directly interacts with and deposits m5C on CTNNB1 caRNA (chromatin-associated RNA). NSUN5-induced recruitment of TET2 to chromatin is independent of its methyltransferase activity. The m5C modification on caRNA is subsequently oxidized into 5-hydroxymethylcytosine (5hmC) by TET2, which is dependent on its binding affinity for Fe2+ and α-KG. Furthermore, NSUN5 enhances the chromatin recruitment of RBFOX2 which acts as a 5hmC-specific reader to recognize and facilitate the degradation of 5hmC caRNA. Notably, hmeRIP-seq analysis reveals numerous mRNA substrates of NSUN5 that potentially undergo this mode of metabolism. In addition, NSUN5 is epigenetically suppressed by DNA methylation and is negatively correlated with IDH1-R132H mutation in glioma patients. Importantly, pharmacological blockage of DNA methylation or IDH1-R132H mutant and CD47/SIRPα signaling synergistically enhances TAM-based phagocytosis and glioma elimination in vivo. Our findings unveil a general mechanism by which NSUN5/TET2/RBFOX2 signaling regulates RNA metabolism and highlight NSUN5 targeting as a potential strategy for glioma immune therapy.

Low phosphorus increases hepatic lipid deposition, oxidative stress and inflammatory response via Acetyl-CoA carboxylase-dependent manner in zebrafish liver cells.

Acetyl-CoA carboxylase (ACC) plays a regulatory role in both fatty acid synthesis and oxidation, controlling the process of lipid deposition in the liver. Given that existing studies have shown a close relationship between low phosphorus (P) and hepatic lipid deposition, this study was conducted to investigate whether ACC plays a crucial role in this relationship. Zebrafish liver cell line (ZFL) was incubated under low P medium (LP, P concentration: 0.77 mg/L) or adequate P medium (AP, P concentration: 35 mg/L) for 240 h. The results showed that, compared with AP-treated cells, LP-treated cells displayed elevated lipid accumulation, and reduced fatty acid ß-oxidation, ATP content, and mitochondrial mass. Furthermore, transcriptomics analysis revealed that LP-treated cells significantly increased lipid synthesis (Acetyl-CoA carboxylases (acc), Stearyl coenzyme A dehydrogenase (scd)) but decreased fatty acid ß-oxidation (Carnitine palmitoyltransferase I (cptI)) and (AMP-activated protein kinase (ampk)) mRNA levels compared to AP-treated cells. The phosphorylation of AMPK and ACC, and the protein expression of CPTI were significantly decreased in LP-treated cells compared with those in AP-treated cells. After 240 h of LP treatment, PF-05175157 (an ACC inhibitor) was supplemented in the LP treatment for an additional 12 h. PF-05175157-treated cells showed higher phosphorylation of ACC, higher protein expression of CPTI, and lower protein expression of FASN, lower TG content, enhanced fatty acid ß-oxidation, increased ATP content, and mitochondrial mass compared with LP-treated cells. PF-05175157 also relieved the LP-induced oxidative stress and inflammatory response. Overall, these findings suggest that ACC is a promising target for treating LP-induced elevation of lipid deposition in ZFL, and can alleviate oxidative stress and inflammatory response.

Omeprazole taken once every other day can effectively prevent aspirin-induced gastrointestinal mucosal damage in rats.

BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.

Association of cooking oil and incident of frailty in older adults: a cohort study.

BACKGROUND: Studies examining the potential association between cooking oil and frailty risk in older adults have produced conflicting outcomes. Therefore, our objective was to explore the relationship between cooking oil (vegetable and animal fat oils), changes in oil usage, and the risk of frailty in older adults. METHODS: We included 4,838 participants aged ≥ 65 years without frailty (frailty index < 0.25) from the 2011 wave of the Chinese Longitudinal Healthy Longevity Survey. Follow-up occurred in the 2014 and 2018 waves. Cox proportional hazard models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) to examine the association between cooking oil and frailty. Additionally, we evaluated the effect of switching cooking oil on frailty during the follow-up period. RESULTS: During a median follow-up of 3.0 (2.8-6.9) years, 1,348 individuals (27.9%) developed frailty. Compared to those using vegetable oil, users of animal fat oil had a lower risk of frailty (HR = 0.72, 95% CI: 0.61-0.85). Participants who switched from vegetable oil to animal fat oil, as well as those consistently using animal fat oil, had lower risks of frailty with HRs of 0.70 (0.52-0.95) and 0.63 (0.51-0.77) respectively, compared to those who consistently used vegetable oil. Conversely, individuals who switched from animal fat oil to vegetable oil experienced an increased risk of frailty (HR: 1.41, 95% CI: 1.01-1.97). CONCLUSIONS: The utilization of animal fat oil in cooking exhibited a reduced frailty risk among older adults. Conversely, transitioning from animal fat oil to vegetable oil may elevate the risk. These findings propose that substituting vegetable oil with animal fat oil in the diet may safeguard against frailty.

Artificial Intelligence-Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice.

OBJECTIVES: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses. METHODS: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians. RESULTS: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864). CONCLUSIONS: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.

[Transition metal accumulation and cellular senescence].

Aging refers to a progressive decline in biological functions, leading to age-related diseases and mortality. The transition metals, including iron, copper, and manganese, play important roles in human physiological and pathological processes. Substantial research has demonstrated that senescent cells accumulate higher levels of transition metals, which in turn accelerates the process of cellular senescence and related diseases through mechanisms such as production of excessive reactive oxygen species (ROS), induction of oxidative stress, DNA damage, and mitochondrial dysfunction. This review article provides a comprehensive overview of the causes of transition metal accumulation in senescent cells, as well as the mechanisms by which it further promotes cellular senescence and related diseases. The aim is to provide insights into anti-aging and treatment of aging-related diseases caused by transition metal accumulation.

Evaluation of reducing the south and reinforcing the north method on postmenopausal atherosclerosis disease based on 4 diagnostic objectifications: A prospective observational study.

Reducing the south and reinforcing the north method (RSRN) has a positive effect on atherosclerosis disease. However, there is a lack of objective standards based on the quantification of 4 diagnostic methods in evaluating the improvement or effectiveness of the treatment. This study aimed to explore the quantitative evaluation of the therapeutic effect of RSRN on postmenopausal atherosclerosis based on the 4 diagnostic methods. The observational prospective cohort study was conducted at Longhua hospital Shanghai University of traditional Chinese medicine. According to the inclusion criteria, 96 patients (disease group) and 38 healthy cases (control group) were selected, the pulse parameters were compared between the 2 groups to demonstrate the reliability and success of the disease model. Then 4 diagnostic information before and after RSRN treatment were collected and statistical analyzed by 1-way analysis of variance (ANOVA) (with Bonferroni correction). Furthermore, social network analysis was used to analyze the changes of symptoms, tongue, pulse, and complexion characteristics before and after treatment. There was a significant difference in pulse parameters between the disease group and the control group. The pulse parameters t1, h3, h3/h1, h4/h1, S, As, and w values in disease group were higher than those in control group, while the h5, h5/h1, and Ad values were lower than those in control group (P < .05). After the treatment of RSRN, the clinical symptoms of patients were greatly improved. The facial color indexes L, a, b values of the disease group at week 6 were different from those at week 0 (P < .05). The overall brightness and chroma of the patient's facial color were significantly improved. The patients had virtual string pulse at week 0, and mainly string I and string II at week 7. The pulse parameters t1, t5, w, w/t, h1, h5, h3/h1, and h5/h1 values at week 7 were different from those at weeks 0, 1, 2 (P < .05); the tongue image was mainly red and crimson, peeling or greasy fur at week 0, while at weeks 6, 7, mainly light red, or thin white tongue. The RSRN method can regulate the complexion, tongue and pulse condition, clinical symptoms of postmenopausal atherosclerosis.

Effectiveness of silver and iodine dressings on wound healing: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effects of silver and iodine dressings on healing time, healing rate, exudate amount, pain and anti-infective efficacy. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Databases including PubMed, Cochrane Library, Embase, Web of Science and CINAHL were surveyed up to May 2024. ELIGIBILITY CRITERIA: Randomised controlled trials comparing silver and iodine dressings on wound healing in humans. DATA EXTRACTION AND SYNTHESIS: Evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Data extraction was done independently by two reviewers, with the risk of bias assessed using the Cochrane tool. Narrative synthesis was performed to evaluate the effects of silver and iodine dressings on healing time, healing rate, pain, exudate amount and anti-infective efficacy. Meta-analysis using Review Manager V.5.4 calculated standardised mean differences for healing time and relative risks for rate to quantify the impacts of the treatments. RESULTS: 17 studies (18 articles) were included. The meta-analysis indicated that silver dressings significantly reduced healing time compared with iodine dressings (SMD=-0.95, 95% CI -1.62 to -0.28, I2=92%, p=0.005, moderate-quality evidence), with no significant difference in enhancing healing rate (RR=1.29, 95% CI 0.90 to 1.85, I2=91%, p=0.16, low-quality evidence). Based on low-quality evidence, for exudate amount (3/17), 66.7% (2/3) of the studies favoured silver dressings over iodine in reducing exudate volume. For pain (7/17), 57.1% (4/7) of the studies reported no significant difference between silver and iodine dressings, while 42.9% (3/7) studies indicated superior pain relief with silver dressings. For anti-infective efficacy (11/13), 54.5% (6/11) of the studies showed equivalence between silver and iodine dressings, while 36.4% (4/11) suggested greater antibacterial efficacy for silver. CONCLUSION: Silver dressings, demonstrating a comparable healing rate to iodine dressings, significantly reduce healing time, suggesting their potential as a superior adjunct in wound care. PROSPERO REGISTRATION NUMBER: CRD42020199602.

Risk Factors for Focal Choroidal Excavation Concurrent with Chorioretinal Disease: Evaluated by Spectral-Domain OCT.

Purpose: To investigate the risk factors for patients with focal choroidal excavation (FCE) and their correlation with chorioretinal diseases. Design: Retrospective cross-sectional study. Subjects: Patients with FCE were enrolled, while healthy subjects were recruited for the control group. Methods: The study collected demographic information, clinical features, and multimodal images. Parameters of FCE identified using spectral-domain OCT (SD-OCT) were manually measured using built-in software and subsequently analyzed statistically. Main Outcome Measures: Subfoveal choroidal thickness (SFCT), subexcavation choroidal thickness (SECT), and the greatest depth and width of each excavation were manually measured using built-in calipers in OCT software. Results: Twenty-one patients (13/8, male/female) with FCE were included in this study. The average age was 45.2 years, and their best-corrected visual acuity (BCVA) was 0.4 logarithm of the minimum angle of resolution (Snellen equivalent, 20/50). Focal choroidal excavation was present in 28 eyes of 21 patients, including isolated FCE (12 eyes) and complicated FCE (16 eyes) with choroidal neovascularization (sCNV), central serous chorioretinopathy, and other conditions. Patients with complicated FCE were significantly older than those isolated FCE (P = 0.015). The SFCT of the healthy subjects was significantly less than that of the fellow eyes of the patients with FCE (P < 0.01), as was that of the eyes with isolated FCE (P < 0.001) and complicated FCE (P < 0.001). The width of excavation was wider in eyes with complicated FCE than in those with isolated FCE (P = 0.001). Hypertransmission defect (HD) was found beneath 15 excavations and was more prevalent in the complicated FCE group than the isolated FCE group (P = 0.023). Conclusions: Focal choroidal excavation appears to be closely related to chorioretinal disorders, and the width of the excavation is a significant indicator for evaluating the risk of chorioretinal diseases. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Application of a Diabetic Foot Smart APP in the measurement of diabetic foot ulcers.

AIMS: In the early stage, we developed an intelligent measurement APP for diabetic foot ulcers, named Diabetic Foot Smart APP. This study aimed to validate the APP in the measurement of ulcer area for diabetic foot ulcer (DFU). METHODS: We selected 150 DFU images to measure the ulcer areas using three assessment tools: the Smart APP software package, the ruler method, and the gold standard Image J software, and compared the measurement results and measurement time of the three tools. The intra-rater and inter-rater reliability were described by Pearson correlation coefficient, intra-group correlation coefficient, and coefficient of variation. RESULTS: The Image J software showed a median ulcer area of 4.02 cm2, with a mean measurement time of 66.37 ± 7.95 s. The ruler method showed a median ulcer area of 5.14 cm2, with a mean measurement time of 171.47 ± 46.43 s. The APP software showed a median ulcer area of 3.70 cm2, with a mean measurement time of 38.25 ± 6.81 s. There were significant differences between the ruler method and the golden standard Image J software (Z = -4.123, p < 0.05), but no significant difference between the APP software and the Image J software (Z = 1.103, p > 0.05). The APP software also showed good inter-rater reliability and intra-rater reliability, with both reaching 0.99. CONCLUSION: The Diabetic Foot Smart APP is a fast and reliable measurement tool with high measurement accuracy that can be easily used in clinical practice for the measurement of ulcer areas of DFU. TRIAL REGISTRATION: Chinese clinical trial registration number: ChiCTR2100047210.

Systematic evaluation of machine learning-enhanced trifocal IOL power selection for axial myopia cataract patients.

PURPOSE: This study aimed to evaluate and optimize intraocular lens (IOL) power selection for cataract patients with high axial myopia receiving trifocal IOLs. DESIGN: A multi-center, retrospective observational case series was conducted. Patients having an axial length ≥26 mm and undergoing cataract surgery with trifocal IOL implanted were studied. METHODS: Preoperative biometric and postoperative outcome data from 139 eyes were collected to train and test various machine learning (ML) models (support vector machine, linear regression, and stacking regressor) using five-fold cross-validation. The models' performance was further validated externally using data from 48 eyes enrolled from other hospitals. Performance of seven IOL calculation formulas (BUII, Kane, EVO, K6, DGS, Holladay I, and SRK/T) were examined with and without ML models. RESULTS: The results of cross-validation revealed improvements across all IOL calculation formulas, especially for K6 and Holladay I. The model increased the percentage of eyes with a prediction error (PE) within ±0.50 D from 71.94% to 79.14% for K6, and from 35.25% to 51.80% for Holladay I. In external validation involving 48 patients from other centers, six out of seven formulas demonstrated a reduction in the mean absolute error (MAE). K6's PE within ±0.50 D improved from 62.50% to 77.08%, and Holladay I from 16.67% to 58.33%. CONCLUSIONS: In this study, we conducted a comprehensive evaluation of seven IOL power calculation formulas in high axial myopia cases and explored the effectiveness of the Stacking Regressor model in augmenting their accuracy. Of these formulas, K6 and Holladay I exhibited the most significant improvements, suggesting that integrating ML may have varying levels of effectiveness across different formulas but holds substantial promise in improving the predictability of IOL power calculations in patients with long eyes.

FACE-Q eye module for measuring patient-reported outcomes in blepharoplasty surgery: A validation study.

This study aimed to conduct a linguistic validation of all FACE-Q eye module scales in German, and to evaluate the reliability and validity of the scales in patients with blepharoplasty. According to international recommendations, all FACE-Q scales and checklists were translated from English to German. Psychometric testing of blepharoplasty surgery-related scales of translated versions were administered to patients with blepharochalasis or dermatochalasis and a history of blepharoplasty surgery (n = 64; 11 scales) or no history of blepharoplasty surgery (n = 65; seven scales), and to a group of control subjects (n = 64; seven scales). Most of the subscales showed acceptable internal consistency, with Cronbach's alphas ranging from 0.75 to 0.97. Intraclass correlation coefficients were high (0.70-0.92), indicating good reliability, with total values of 0.63 (95% CI 0.46-0.76) and 0.68 (95% CI 0.53-0.80) for the upper eyelid and social function scores, respectively. There was good discriminability between pre- and post-blepharoplasty patients and normal subjects (p < 0.05). The German-language version of the FACE-Q eye module is a successfully validated and helpful tool for assessing outcomes after blepharoplasty surgery, especially with respect to 'satisfaction with overall facial appearance', 'psychological well-being, social function', 'decision satisfaction, outcome satisfaction', and 'early-life impact recovery'.

Correction: Accelerated weight gain, prematurity, and the risk of childhood obesity: A meta-analysis and systematic review.

[This corrects the article DOI: 10.1371/journal.pone.0232238.].

FedEYE: A scalable and flexible end-to-end federated learning platform for ophthalmology.

Data-driven machine learning, as a promising approach, possesses the capability to build high-quality, exact, and robust models from ophthalmic medical data. Ophthalmic medical data, however, presently exist across disparate data silos with privacy limitations, making centralized training challenging. While ophthalmologists may not specialize in machine learning and artificial intelligence (AI), considerable impediments arise in the associated realm of research. To address these issues, we design and develop FedEYE, a scalable and flexible end-to-end ophthalmic federated learning platform. During FedEYE design, we adhere to four fundamental design principles, ensuring that ophthalmologists can effortlessly create independent and federated AI research tasks. Benefiting from the design principles and architecture of FedEYE, it encloses numerous key features, including rich and customizable capabilities, separation of concerns, scalability, and flexible deployment. We also validated the applicability of FedEYE by employing several prevalent neural networks on ophthalmic disease image classification tasks.

Efficient Expression and Application of a Modified Rhizomucor miehei Lipase for Simultaneous Production of Biodiesel and Eicosapentaenoic Acid Ethyl Ester from Nannochloropsis Oil.

Few reports exist on one-step enzymatic methods for the simultaneous production of biodiesel and eicosapentaenoic acid ethyl ester (EPA-EE), a high-value pharmaceutical compound. This study aimed to efficiently express Rhizomucor miehei lipase (pRML) in Pichia pastoris X-33 via propeptide mutation and high-copy strain screening. The mutated enzyme was then used to simultaneously catalyze the production of both biodiesel and EPA-EE. The P46N mutation in the propeptide (P46N-pRML) significantly boosted its production, with the four-copy strain increasing enzyme yield by 3.7-fold, reaching 3425 U/mL. Meanwhile, its optimal temperature increased to 45-50 °C, pH expanded to 7.0-8.0, specific activity doubled, Km reduced to one-third, and kcat/Km increased 7-fold. Notably, P46N-pRML efficiently converts Nannochloropsis gaditana oil's eicosapentaenoic acid (EPA). Under optimal conditions, it achieves up to 93% biodiesel and 92% EPA-EE yields in 9 h. Our study introduces a novel, efficient one-step green method to produce both biodiesel and EPA-EE using this advanced enzyme.

Two-stage deep neural network for diagnosing fungal keratitis via in vivo confocal microscopy images.

Timely and effective diagnosis of fungal keratitis (FK) is necessary for suitable treatment and avoiding irreversible vision loss for patients. In vivo confocal microscopy (IVCM) has been widely adopted to guide the FK diagnosis. We present a deep learning framework for diagnosing fungal keratitis using IVCM images to assist ophthalmologists. Inspired by the real diagnostic process, our method employs a two-stage deep architecture for diagnostic predictions based on both image-level and sequence-level information. To the best of our knowledge, we collected the largest dataset with 96,632 IVCM images in total with expert labeling to train and evaluate our method. The specificity and sensitivity of our method in diagnosing FK on the unseen test set achieved 96.65% and 97.57%, comparable or better than experienced ophthalmologists. The network can provide image-level, sequence-level and patient-level diagnostic suggestions to physicians. The results show great promise for assisting ophthalmologists in FK diagnosis.

Overcoming therapeutic resistance in oncolytic herpes virotherapy by targeting IGF2BP3-induced NETosis in malignant glioma.

Oncolytic virotherapy holds promise for cancer treatment, but the factors determining its oncolytic activity remain unclear. Neutrophil extracellular traps (NETs) are associated with cancer progression, yet their formation mechanism and role in oncolytic virotherapy remain elusive. In this study, we demonstrate that, in glioma, upregulation of IGF2BP3 enhances the expression of E3 ubiquitin protein ligase MIB1, promoting FTO degradation via the ubiquitin-proteasome pathway. This results in increased m6A-mediated CSF3 release and NET formation. Oncolytic herpes simplex virus (oHSV) stimulates IGF2BP3-induced NET formation in malignant glioma. In glioma models in female mice, a BET inhibitor enhances the oncolytic activity of oHSV by impeding IGF2BP3-induced NETosis, reinforcing virus replication through BRD4 recruitment with the CDK9/RPB-1 complex to HSV gene promoters. Our findings unveil the regulation of m6A-mediated NET formation, highlight oncolytic virus-induced NETosis as a critical checkpoint hindering oncolytic potential, and propose targeting NETosis as a strategy to overcome resistance in oncolytic virotherapy.

Exploration of the effect and mechanism of Scutellaria barbata D. Don in the treatment of ovarian cancer based on network pharmacology and in vitro experimental verification.

The mortality rate of ovarian cancer is the highest among gynecological cancers, posing a serious threat to women health and life. Scutellaria barbata D. Don (SBD) can effectively treat ovarian cancer. However, its mechanism of action is unclear. The aim of this study was to elucidate the mechanism of SBD in the treatment of ovarian cancer using network pharmacology, and to verify the experimental results using human ovarian cancer SKOV3 cells. The Herb and Disease Gene databases were searched to identify common targets of SBD and ovarian cancer. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Protein-Protein Interaction (PPI) network analyses were performed to identify the potential molecular mechanisms behind SBD. Finally, the molecular docking and main possible pathways were verified by experimental studies. Cell proliferation, the mRNA expression level of key genes and signaling pathway were all investigated and evaluated in vitro. A total of 29 bioactive ingredients and 137 common targets in SBD were found to inhibit ovarian cancer development. The active ingredients identified include quercetin, luteolin, and wogonin. Analysis of the PPI network showed that AKT1, VEGFA, JUN, TNF, and Caspase-3 shared centrality among all target genes. The results of the KEGG pathway analysis indicated that the cancer pathway, PI3K-Akt signaling pathway, and MAPK signaling pathways mediated the effects of SBD against ovarian cancer progression. Cell experiments showed that quercetin, luteolin, and wogonin inhibited the proliferation and clone formation of SKOV3 cells and regulated mRNA expression of 5 key genes by inhibiting PI3K/Akt signaling pathway. Our results demonstrate that SBD exerted anti-ovarian cancer effects through its key components quercetin, luteolin and wogonin. Mechanistically, its anti-cancer effects were mediated by inhibition of the PI3K/Akt signaling pathways. Therefore, SBD might be a candidate drug for ovarian cancer treatment.

Case report: One case of umbilical vein thrombosis in the second trimester with associated portal vein thrombosis after childbirth.

Background: Umbilical vein thrombosis is a rare pregnancy complication, that is difficult to detect prenatally but can lead to poor fetal outcomes. Case presentation: We described a 33-year-old primiparae who was identified as having umbilical vein thrombosis by ultrasound at 21 weeks gestation, and the neonate was found to have a portal vein thrombus after delivery. Following enoxaparin anticoagulant therapy, the thrombus disappeared within 4 weeks. No thrombus formation occured during the 10-month follow-up, and the baby was in excellent clinical condition. Conclusion: Owing to the poor fetal outcomes related to umbilical thrombosis, pay attention to abnormal clinical signs during prenatal ultrasound, fetal heart monitoring and counting fetal movements can help in the early identification of umbilical cord thrombosis.The findings highlight the importance of regular prenatal ultrasound evaluation, enabling early detection and monitoring of any anomalies or vascular abnormalities related to the fetal umbilical vein. Further research is warranted to explore the clinical implications and long-term outcomes associated with these findings.

Characterization of a Novel Polysaccharide Derived from Rhizospheric Paecilomyces vaniformisi and Its Mechanism for Enhancing Salinity Resistance in Rice Seedlings.

Soil salinity is an important limiting factor in agricultural production. Rhizospheric fungi can potentially enhance crop salinity tolerance, but the precise role of signaling substances is still to be systematically elucidated. A rhizospheric fungus identified as Paecilomyces vaniformisi was found to enhance the salinity tolerance of rice seedlings. In this study, a novel polysaccharide (PPL2b) was isolated from P. vaniformisi and identified as consisting of Manp, Glcp, GalpA, and Galp. In a further study, PPL2b showed significant activity in alleviating salinity stress-induced growth inhibition in rice seedlings. The results indicated that under salinity stress, PPL2b enhances seed germination, plant growth (height and biomass), and biochemical parameters (soluble sugar and protein contents). Additionally, PPL2b regulates genes such as SOS1 and SKOR to decrease K+ efflux and increase Na+ efflux. PPL2b increased the expression and activity of genes related to antioxidant enzymes and nonenzyme substances in salinity-induced oxidative stress. Further study indicated that PPL2b plays a crucial role in regulating osmotic substances, such as proline and betaine, in maintaining the osmotic balance. It also modulates plant hormones to promote rice seedling growth and enhance their tolerance to soil salinity. The variables interacted and were divided into two groups (PC1 77.39% and PC2 18.77%) based on their relative values. Therefore, these findings indicate that PPL2b from P. vaniformisi can alleviate the inhibitory effects of salinity stress on root development, osmotic adjustment, ion balance, oxidative stress balance, and growth of rice seedlings. Furthermore, it suggests that polysaccharides produced by rhizospheric fungi could be utilized to enhance crop tolerance to salinity.