Antifungal Activity of Phloroglucinol Derivatives against Botrytis cinerea and Monilinia fructicola.

Naturally derived compounds show promise as treatments for microbial infections. Polyphenols, abundantly found in various plants, fruits, and vegetables, are noted for their physiological benefits including antimicrobial effects. This study introduced a new set of acylated phloroglucinol derivatives, synthesized and tested for their antifungal activity in vitro against seven different pathogenic fungi. The standout compound, 3-methyl-1-(2,4,6-trihydroxyphenyl) butan-1-one (2b), exhibited remarkable fungicidal strength, with EC50 values of 1.39 µg/mL against Botrytis cinerea and 1.18 µg/mL against Monilinia fructicola, outperforming previously screened phenolic compounds. When tested in vivo, 2b demonstrated effective antifungal properties, with cure rates of 76.26% for brown rot and 83.35% for gray mold at a concentration of 200 µg/mL, rivaling the commercial fungicide Pyrimethanil in its efficacy against B. cinerea. Preliminary research suggests that 2b's antifungal mechanism may involve the disruption of spore germination, damage to the fungal cell membrane, and leakage of cellular contents. These results indicate that compound 2b has excellent fungicidal properties against B. cinerea and holds potential as a treatment for gray mold.

Variability in Lipid Profiles During Young Adulthood and the Risk of Coronary Artery Calcium Incidence in Midlife: Insights From the CARDIA Study.

BACKGROUND: Intraindividual variability in lipid profiles is recognized as a potential predictor of cardiovascular events. However, the influence of early adulthood lipid profile variability along with mean lipid levels on future coronary artery calcium (CAC) incidence remains unclear. METHODS: A total of 2395 participants (41.6% men; mean±SD age, 40.2±3.6 years) with initial CAC =0 from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included. Serial lipid measurements were obtained to calculate mean levels and variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides. CAC incidence was defined as CAC >0 at follow-up. RESULTS: During a mean follow-up of 9.0 years, 534 individuals (22.3%) exhibited CAC incidence. Higher mean levels of total cholesterol, LDL-C, and non-HDL-C were associated with a greater risk of future CAC incidence. Similarly, 1-SD increment of lipid variability, as assessed by variability independent of the mean, was associated with an increased risk of CAC incidence (LDL-C: hazard ratio, 1.139 [95% CI, 1.048-1.238]; P=0.002; non-HDL-C: hazard ratio, 1.102 [95% CI, 1.014-1.198]; P=0.022; and triglycerides: hazard ratio, 1.480 [95% CI, 1.384-1.582]; P<0.001). Combination analyses demonstrated that participants with both high lipid levels and high variability in lipid profiles (LDL-C and non-HDL-C) faced the greatest risk of CAC incidence. Specifically, elevated variability of LDL-C was associated with an additional risk of CAC incidence even in low mean levels of LDL-C (hazard ratio, 1.396 [95% CI, 1.106-1.763]; P=0.005). These findings remained robust across a series of sensitivity and subgroup analyses. CONCLUSIONS: Elevated variability in LDL-C and non-HDL-C during young adulthood was associated with an increased risk of CAC incidence in midlife, especially among those with high mean levels of atherogenic lipoproteins. These findings highlight the importance of maintaining consistently low levels of atherogenic lipids throughout early adulthood to reduce subclinical atherosclerosis in midlife. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005130.

Design, Synthesis, and Antimicrobial Activity Evaluation of Novel Isocryptolepine Derivatives against Phytopathogenic Fungi and Bacteria.

This research adopted the Fischer indole synthesis method to continue constructing a novel drug-like chemical entity based on the guidance of isocryptolepine and obtained four series of derivatives: Y, Da, Db, and Dc. The antimicrobial activity of these derivatives against plant pathogens was further evaluated. The results showed that Dc-2 had the best antifungal effect against Botrytis cinerea, and its EC50 value was up to 1.29 µg/mL. In addition, an in vivo activity test showed that the protective effect of Dc-2 on apples was 82.2% at 200 µg/mL, which was better than that of Pyrimethanil (45.4%). Meanwhile, it was found by scanning electron microscopy and transmission electron microscopy that the compound Dc-2 affected the morphology of mycelia. The compound Dc-2 was found to damage the cell membrane by PI and ROS staining. Through experiments such as leakage of cell contents, it was found that the compound Dc-2 changed the permeability of the cell membrane and caused the leakage of substances in the cell. According to the above studies, compound Dc-2 can be used as a candidate lead compound for further structural optimization and development.

Causal Association of Golgi Protein 73 With Coronary Artery Disease: Evidence from Proteomics and Mendelian Randomization.

Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD.

Current development and structure-activity relationship study of berberine derivatives.

Berberine is a quaternary ammonium isoquinoline alkaloid derived from traditional Chinese medicines Coptis chinensis and Phellodendron chinense. It has many pharmacological activities such as hypoglycemic, hypolipidemic, anti-tumor, antimicrobial and anti-inflammatory. Through structural modifications at various sites of berberine, the introduction of different groups can change berberine's physical and chemical properties, thereby improving the biological activity and clinical efficacy, and expanding the scope of application. This paper reviews the research progress and structure-activity relationships of berberine in recent years, aiming to provide valuable insights for the exploration of novel berberine derivatives.

Prenylated Flavonoids Isolated from the Root of Sophora flavescens as Potent Antifungal Agents against Botrytis cinerea.

Sophora flavescens, a traditional Chinese herb, produces a wide range of secondary metabolites with a broad spectrum of biological activities. In this study, we isolated six isopentenyl flavonoids (1-6) from the roots of S. flavescens and evaluated their activities against phytopathogenic fungi. In vitro activities showed that kurarinone and sophoraflavanone G displayed broad spectrum and superior activities, among which sophoraflavanone G displayed excellent activity against tested fungi, with EC50 values ranging from 4.76 to 13.94 µg/mL. Notably, kurarinone was easily purified and showed potential activity against Rhizoctonia solani, Botrytis cinerea, and Fusarium graminearum with EC50 values of 16.12, 16.55, and 16.99 µg/mL, respectively. Consequently, we initially investigated the mechanism of kurarinone against B. cinerea. It was found that kurarinone disrupted cell wall components, impaired cell membrane integrity, increased cell membrane permeability, and affected cellular energy metabolism, thereby exerting its effect against B. cinerea. Therefore, kurarinone is expected to be a potential candidate for the development of plant fungicides.

Blood pressure variability and prognostic significance in traumatic brain injury: analysis of the eICU-CRD database.

BACKGROUND: Preliminary evidence demonstrates that visit-to-visit systolic blood pressure (SBP) variability is a prognostic factor of TBI. However, literature regarding the impact of initial blood pressure management on the outcomes of TBI patients is limited. We aimed to further validate the clinical significance of BPV on the prognostic outcomes of patients with TBI. METHODS: We performed the analysis by using individual patient-level data acquired from the eICU-CRD, which collected 200,859 ICU admissions of 139,367 patients in 2014 and 2015 from 208 US hospitals. Adult patients with traumatic intraparenchymal hemorrhage or contusion were included. The primary outcome was in-hospital mortality and the secondary outcome was discharge-home rate. Blood pressure variability (BPV) was calculated according to standard criteria: at least six measurements were taken in the first 24 h (hyperacute group) and 36 over days 2-7 (acute group). We estimated the associations between BPV and outcomes with logistic and proportional odds regression models. The key parameter for BPV was standard deviation (SD) of SBP, categorized into quintiles. We also calculated the average real variability (ARV), as well as maximum, minimum, and mean SBP for comparison in our analysis. RESULTS: We studied 1486 patients in the hyperacute group and 857 in the acute group. SD of SBP had a significant association with the in-hospital mortality for both the hyperacute group (highest quintile adjusted OR 2.28 95% CI 1.18-4.42; ptrend<0.001) and the acute group (highest quintile adjusted OR 2.17, 95% CI 1.08-4.36; ptrend<0.001). The strongest predictors of primary outcome were SD of SBP in the hyperacute phase and minimum SBP in the acute phase. Associations were similar for the discharge-home rate (for the hyperacute group, highest quintile adjusted OR 0.58, 95% CI 0.37-0.89; ptrend<0.001; for the acute group OR 0.55, 95% CI 0.32-0.95; ptrend<0.001). CONCLUSION: Systolic BPV seems to predict a poor outcome in patients with TBI. The benefits of early treatment to maintain appropriate SBP level might be enhanced by smooth and sustained control.

Epidemiological features and temporal trends of the co-infection between HIV and tuberculosis, 1990-2021: findings from the Global Burden of Disease Study 2021.

BACKGROUND: The co-infection of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) poses a significant clinical challenge and is a major global public health issue. This study aims to elucidate the disease burden of HIV-TB co-infection in global, regions and countries, providing critical information for policy decisions to curb the HIV-TB epidemic. METHODS: The ecological time-series study used data from the Global Burden of Disease (GBD) Study 2021. The data encompass the numbers of incidence, prevalence, mortality, and disability-adjusted life year (DALY), as well as age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate for HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis (HIV-MDR-TB), and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) from 1990 to 2021. from 1990 to 2021. The estimated annual percentage change (EAPC) of rates, with 95% confidence intervals (CIs), was calculated. RESULTS: In 2021, the global ASIR for HIV-DS-TB was 11.59 per 100,000 population (95% UI: 0.37-13.05 per 100,000 population), 0.55 per 100,000 population (95% UI: 0.38-0.81 per 100,000 population), for HIV-MDR-TB, and 0.02 per 100,000 population (95% UI: 0.01-0.03 per 100,000 population) for HIV-XDR-TB. The EAPC for the ASIR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.71 (95% CI: 1.92-7.59) and 13.63 (95% CI: 9.44-18.01), respectively. The global ASMR for HIV-DS-TB was 2.22 per 100,000 population (95% UI: 1.73-2.74 per 100,000 population), 0.21 per 100,000 population (95% UI: 0.09-0.39 per 100,000 population) for HIV-MDR-TB, and 0.01 per 100,000 population (95% UI: 0.00-0.03 per 100,000 population) for HIV-XDR-TB in 2021. The EAPC for the ASMR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.78 (95% CI: 1.32-8.32) and 10.00 (95% CI: 6.09-14.05), respectively. CONCLUSIONS: The findings indicate that enhancing diagnostic and treatment strategies, strengthening healthcare infrastructure, increasing access to quality medical care, and improving public health education are essential to combat HIV-TB co-infection.

Anti-swelling Microporous Membrane for High-capacity and Long-life Zn-I2 Batteries.

Zinc-iodine (Zn-I2) batteries are gaining popularity due to cost-effectiveness and ease of manufacturing. However, challenges like polyiodide shuttle effect and Zn dendrite growth hinder their practical application. Here, we report a cation exchange membrane to simultaneously prevent the polyiodide shuttle effect and regulate Zn2+ deposition. Comprised of rigid polymers, this membrane shows superior swelling resistance and ion selectivity compared to commercial Nafion. The resulting Zn-I2 battery exhibits a high Coulombic efficiency of 99.4% and low self-discharge rate of 4.47% after 48 h rest. By directing a uniform Zn2+ flux, the membrane promotes a homogeneous electric field, resulting in a dendrite-free Zn surface. Moreover, its microporous structure enables pre-adsorption of additional active materials prior to battery assembly, boosting battery capacity to 287 mA h g-1 at 0.1 A g-1. At 2 A g-1, the battery exhibits a steady running for 10,000 cycles with capacity retention up to 96.1%, demonstrating high durability of the membrane. The practicality of the membrane is validated via a high loading (35 mg cm-2) pouch cell with impressive cycling stability, paving a way for membrane design towards advanced Zn-I2 batteries.

Comprehensive Multiple Risk Factor Control in Type 2 Diabetes to Mitigate Heart Failure Risk: Insights From a Prospective Cohort Study.

OBJECTIVE: The impact of comprehensive risk factor control on heart failure (HF) risk and HF-free survival time in individuals with type 2 diabetes (T2D) was evaluated in this study. RESEARCH DESIGN AND METHODS: This prospective study included 11,949 individuals diagnosed with T2D, matched with 47,796 non-T2D control study participants from the UK Biobank cohort. The degree of comprehensive risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, BMI, LDL cholesterol, hemoglobin A1c, renal function, smoking, diet, and physical activity. Cox proportional hazards models were used to measure the associations between the degree of risk factor control and HF risk. Irwin's restricted mean was used to evaluate HF-free survival time. RESULTS: During a median follow-up of 12.3 years, 702 individuals (5.87%) with T2D and 1,402 matched control participants (2.93%) developed HF. Each additional risk factor controlled was associated with an average 19% lower risk of HF. Optimal control of at least six risk factors was associated with a 67% lower HF risk (hazard ratio [HR] 0.33; 95% CI 0.20, 0.54). BMI was the primary attributable risk factor for HF. Notably, the excess risk of HF associated with T2D could be attenuated to levels comparable to those of non-T2D control participants when individuals had a high degree of risk factor control (HR 0.66; 95% CI 0.40, 1.07), and they exhibited a longer HF-free survival time. CONCLUSIONS: Comprehensive management of risk factors is inversely associated with HF risk, and optimal risk factor control may prolong HF-free survival time among individuals with T2D.

Protocol for evaluating S-acylated protein membrane affinity using protein-lipid conjugates.

S-acylation of proteins allows their association with membranes. Here, we present a protocol for establishing a platform for membrane affinity evaluation of S-acylated proteins in vitro. We describe steps for preparing lipid-maleimide compounds, mCherry-p62 recombinant proteins, and total cellular membranes. We then detail procedures for synthesizing protein-lipid conjugates using lipid-maleimide compounds and recombinant proteins and evaluating the membrane affinity of protein-lipid conjugates. For complete details on the use and execution of this protocol, please refer to Huang Xue et al.1.

Identifying cooperating cancer driver genes in individual patients through hypergraph random walk.

OBJECTIVE: Identifying cancer driver genes, especially rare or patient-specific cancer driver genes, is a primary goal in cancer therapy. Although researchers have proposed some methods to tackle this problem, these methods mostly identify cancer driver genes at single gene level, overlooking the cooperative relationship among cancer driver genes. Identifying cooperating cancer driver genes in individual patients is pivotal for understanding cancer etiology and advancing the development of personalized therapies. METHODS: Here, we propose a novel Personalized Cooperating cancer Driver Genes (PCoDG) method by using hypergraph random walk to identify the cancer driver genes that cooperatively drive individual patient cancer progression. By leveraging the powerful ability of hypergraph in representing multi-way relationships, PCoDG first employs the personalized hypergraph to depict the complex interactions among mutated genes and differentially expressed genes of an individual patient. Then, a hypergraph random walk algorithm based on hyperedge similarity is utilized to calculate the importance scores of mutated genes, integrating these scores with signaling pathway data to identify the cooperating cancer driver genes in individual patients. RESULTS: The experimental results on three TCGA cancer datasets (i.e., BRCA, LUAD, and COADREAD) demonstrate the effectiveness of PCoDG in identifying personalized cooperating cancer driver genes. These genes identified by PCoDG not only offer valuable insights into patient stratification correlating with clinical outcomes, but also provide an useful reference resource for tailoring personalized treatments. CONCLUSION: We propose a novel method that can effectively identify cooperating cancer driver genes for individual patients, thereby deepening our understanding of the cooperative relationship among personalized cancer driver genes and advancing the development of precision oncology.

Baseline Performance of Ultrasound-Based Strategies in Breast Cancer Screening Among Chinese Women.

RATIONALE AND OBJECTIVE: There is a notable absence of robust evidence on the efficacy of ultrasound-based breast cancer screening strategies, particularly in populations with a high prevalence of dense breasts. Our study addresses this gap by evaluating the effectiveness of such strategies in Chinese women, thereby enriching the evidence base for identifying the most efficacious screening approaches for women with dense breast tissue. METHODS: Conducted from October 2018 to August 2022 in Central China, this prospective cohort study enrolled 8996 women aged 35-64 years, divided into two age groups (35-44 and 45-64 years). Participants were screened for breast cancer using hand-held ultrasound (HHUS) and automated breast ultrasound system (ABUS), with the older age group also receiving full-field digital mammography (FFDM). The Breast Imaging Reporting and Data System (BI-RADS) was employed for image interpretation, with abnormal results indicated by BI-RADS 4/5, necessitating a biopsy; BI-RADS 3 required follow-up within 6-12 months by primary screening strategies; and BI-RADS 1/2 were classified as negative. RESULTS: Among the screened women, 29 cases of breast cancer were identified, with 4 (1.3‰) in the 35-44 years age group and 25 (4.2‰) in the 45-64 years age group. In the younger age group, HHUS and ABUS performed equally well, with no significant difference in their AUC values (0.8678 vs. 0.8679, P > 0.05). For the older age group, ABUS as a standalone strategy (AUC 0.9935) and both supplemental screening methods (HHUS with FFDM, AUC 0.9920; ABUS with FFDM, AUC 0.9928) outperformed FFDM alone (AUC 0.8983, P < 0.05). However, there was no significant difference between HHUS alone and FFDM alone (AUC 0.9529 vs. 0.8983, P > 0.05). CONCLUSION: The findings indicate that both HHUS and ABUS exhibit strong performance as independent breast cancer screening strategies, with ABUS demonstrating superior potential. However, the integration of FFDM with these ultrasound techniques did not confer a substantial improvement in the overall effectiveness of the screening process.

Identification and Functional Characterization of Carboxylesterase Genes Involved in Spirodiclofen Resistance in Panonychus citri (McGregor).

Overexpression of carboxyl/cholinesterase (CCE) genes has been reported to be associated with many cases of pesticide resistance in arthropods. However, it has been rarely documented that CCE genes participate in spirodiclofen resistance in Panonychus citri. In previous research, we found that spirodiclofen resistance is related to increased P450 and CCE enzyme activities in P. citri. In this study, we identified two CCE genes, PcCCE3 and PcCCE5, which were significantly upregulated in spirodiclofen-resistant strain and after exposure to spirodiclofen. RNA interference of PcCCE3 and PcCCE5 increased the spirodiclofen susceptibility in P. citri. In vitro metabolism indicated that PcCCE3 and PcCCE5 could interact with spirodiclofen, but metabolites were detected only in the PcCCE3 treatment. Our results indicated that PcCCE3 participates in spirodiclofen resistance through direct metabolism, and PcCCE5 may be involved in the spirodiclofen resistance by passive binding and sequestration, which provides new insights into spirodiclofen resistance in P. citri.

Thyroxine regulates pig Sertoli cell line proliferation and maturation through the IKK/NFκB and p38 MAPK signaling pathways.

The aim of this study was to investigate the signaling pathways involved in the proliferation and differentiation of pig Sertoli cells (SCs) mediated by thyroid hormone (T3) to provide a theoretical and practical basis for enhancing pig semen production. The effects of different concentrations of T3 on the proliferation of pig SCs were evaluated using the CCK8 assay. The impact of T3 on the proliferation and differentiation of pig SCs was further examined using RNA-seq, qPCR, and Western Blotting techniques. Additionally, the involvement of the p38 MAPK and NFκB pathways in mediating the effects of T3 on SCs proliferation and differentiation was investigated. Our findings revealed a strong correlation between the dosage of T3 and the inhibition of pig SCs proliferation and promotion of maturation. T3 regulated the activation state of the NFκB signaling pathway by upregulating IKKα, downregulating IKKß, and promoting IκB phosphorylation. Furthermore, T3 facilitated SCs maturation by upregulating AR and FSHR expression while downregulating KRT-18. In conclusion, T3 inhibits pig SCs proliferation and promote pig SCs maturation through the IKK/NFκB and p38 MAPK pathways. These findings provide valuable insights into the mechanisms by which T3 influences the proliferation and maturation of pig SCs.

Promoting Proton Donation through Hydrogen Bond Breaking on Carbon Nitride for Enhanced H2O2 Photosynthesis.

Photocatalytic H2O2 production has attracted much attention as an alternative way to the industrial anthraquinone oxidation process but is limited by the weak interaction between the catalysts and reactants as well as inefficient proton transfer. Herein, we report on a hydrogen-bond-broken strategy in carbon nitride for the enhancement of H2O2 photosynthesis without any sacrificial agent. The H2O2 photosynthesis is promoted by the hydrogen bond formation between the exposed N atoms on hydrogen-bond-broken carbon nitride and H2O molecules, which enhances proton-coupled electron transfer and therefore the photocatalytic activity. The exposed N atoms serve as proton buffering sites for the proton transfer from H2O molecules to carbon nitride. The H2O2 photosynthesis is also enhanced through the enhanced adsorption and reduction of O2 gas toward H2O2 on hydrogen-bond-broken carbon nitride because of the formation of nitrogen vacancies (NVs) and cyano groups after the intralayer hydrogen bond breaking on carbon nitride. A high light-to-chemical conversion efficiency (LCCE) value of 3.85% is achieved. O2 and H2O molecules are found to undergo a one-step two-electron reduction pathway by photogenerated hot electrons and a four-electron oxidation process to produce O2 gas, respectively. Density functional theory (DFT) calculations validate the O2 adsorption and reaction pathways. This study elucidates the significance of the hydrogen bond formation between the catalyst and reactants, which greatly increases the proton tunneling dynamics.

Identification and Validation of a Novel Tertiary Lymphoid Structures-Related Prognostic Gene Signature in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors originating from the digestive system. Tertiary lymphoid structures (TLS), non-lymphoid tissues outside of the lymphoid organs, are closely connected to chronic inflammation and tumorigenesis. However, the detailed relationship between TLS and HCC prognosis remained unclear. In this study, we aimed to construct a TLS-related gene signature for predicting the prognosis of HCC patients. Methods: The Cancer Genome Atlas (TCGA) clinical data from 369 HCC tissues and 50 normal liver tissues were utilized to examine the differential expression of TLS-related genes. Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Furthermore, Cox regression analysis was applied to identify whether the TLS score could be employed as an independent prognosis factor. A nomogram was developed to predict the survival probability of HCC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for TLS-related genes. Genetic mutation analysis, the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA) were used to assess the tumor mutation landscape and immune infiltration. Finally, the role of the TLS score in HCC therapy was investigated. Results: Six genes were included in the construction of our prognostic model (CETP, DNASE1L3, PLAC8, SKAP1, C7, and VNN2), and we validated its accuracy. Survival analysis showed that patients in the high-TLS score group had a significantly better overall survival than those in the low-TLS score group. Univariate, multivariate Cox regression analysis and the establishment of a nomogram indicated that the TLS score could independently function as a potential prognostic marker. A significant association between TLS score and immunity was revealed by an analysis of gene alterations and immune cell infiltration. In addition, two subtypes of the TLS score could accurately predict the effectiveness of sorafenib, transcatheter arterial chemoembolization (TACE), and immunotherapy in HCC patients. Conclusion: In this research, we conducted and validated a prognostic model associated with TLS that may be helpful for predicting clinical outcomes and treatment responsiveness for HCC patients.

Acute primary angle closure during the Omicron outbreak.

AIM: To investigate Omicron's impact on clinical presentation of acute primary angle closure (APAC) in China. METHODS: A consecutive case series with historical controls was conducted at Shenzhen Eye Hospital, the largest specialized hospital in Shenzhen, China. Medical records from a two-month period during the Omicron pandemic (December 1, 2022, to January 31, 2023) were compared with records from two control groups (12/2018-1/2019 and 12/2021-1/2022) before pandemic. Patients with APAC were included, and the prevalence of APAC and demographic characteristics in Omicron-infected and non-infected patients were compared. RESULTS: Seventy-one (23.43%) out of 303 patients were diagnosed with APAC in the pandemic cohort, which was 2.98 and 2.61 times higher than that in control cohorts (7.87% in 2019, 8.96% in 2022, P<0.001). The pandemic cohort has significantly higher Omicron-infected rate (78.87% vs 0 vs 0; P<0.001), lower proportion of glaucoma history (16.90% vs 42.86% vs 41.67%, P=0.005), higher surgical rate (95.77% vs 83.33% vs 78.57%, P=0.024), higher total medical costs and larger pupil diameter (5.63±0.15 vs 4.68±0.15 vs 4.69±0.22 mm, P<0.01). In 83% Omicron-infected patients, ocular symptoms appeared within 3d after systemic symptoms onset. In multivariate analysis, Omicron infection (P<0.001) was the only independent predictor of pupil diameter. CONCLUSION: In the Omicron epidemic in China, there is an increase of prevalence and severity of APAC, particularly focusing on the first 3d following infection.

Malignant glaucoma treated by low-dose laser cycloplasty: a 1-year multicenter prospective non-comparative study.

AIM: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients. METHODS: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo. Intraocular pressure (IOP), number of glaucoma medications, anterior chamber depth (ACD), and complications were recorded. Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy. Recurrence was defined by the presence of a shallow or flat anterior chamber after initial recovery from treatment. RESULTS: A total of 34 eyes received LCP. Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg (P<0.001) with 2.9±1.6 medications (P=0.046) at 1d, and 17.4±6.7 mm Hg (P<0.001) with 1.3±1.7 medications (P<0.001) at 12mo. The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo, respectively. A total of 32 (94.1%) eyes achieved initial anatomical success. During follow-up, 2 (5.9%) eyes failed and 8 (23.5%) eyes relapsed, yielding a 12-month anatomical success rate of 64.3%. Complications including anterior synechia (8.82%), choroidal/ciliary detachment (5.88%) and hypopyon (2.94%) were observed within 1wk. CONCLUSION: LCP is simple, safe, and effective in reforming the anterior chamber in malignant glaucoma.