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Abstract Objective Our study tried to evaluate the prognostic utility of preoperative serum cyfra21-1 in patients with penile squamous cell carcinoma (PSCC). Methods This retrospective study analyzed data from 94 patients who underwent either partial or radical penectomy accompanied by bilateral inguinal or pelvic lymphadenectomy at our institution from 2010 to 2018. The median duration of follow-up was 66.5 months. Serum cyfra21-1 concentrations were quantified through enzyme-linked immunosorbent assay, with patients classified into two groups based on cyfra21-1 levels (≤ 3.30 ng/ml and > 3.30 ng/ml). The impact of cyfra21-1 levels on clinical outcomes was evaluated. Results Among the 94 patients, 68 (72.3%) had normal cyfra21-1 levels, while 26 (27.6%) exhibited elevated cyfra21-1 levels. During the follow-up period, 38 patients (40.4%) experienced relapse, and 35 patients (37.2%) died from PSCC. A significantly higher occurrence of advanced pathological grades was observed in the elevated cyfra21-1 group compared to the normal group (P = 0.029). Patients with elevated cyfra21-1 levels had significantly worse disease-free survival (DFS) and disease-specific survival (DSS) than those with normal levels (P

Abstract Background Studies have shown that m6A modification is related to the occurrence and development of papillary thyroid carcinoma (PTC). The disorder of succinic acid metabolism is associated with the occurrence and development of various tumors. However, there are few studies based on m6A and succinate metabolism-related genes (SMRGs) in PTC. Methods The TCGA-Thyroid carcinoma (THCA), GSE33630, 1159 SMRGs, and 23 m6A regulatory factors were collected from the online databases. Subsequently, the differentially expressed genes (DEGs) were selected between PTC (Tumor) and Normal samples. The overlapping genes among the DEGs, m6A, and SMRGs were applied to screen the biomarkers. Using the 3 machine-learning algorithms, the biomarkers were determined based on the overlapping genes. Next, the biomarkers were evaluated by the ROC curve and expression analysis in TCGA-THCA and GSE33630. Then, the overall survival (OS) differences were compared between the high-and low-expression biomarkers. Finally, immune infiltration analysis, molecular regulatory network, and drug prediction were performed based on the biomarkers. Results In TCGA-THCA, there were 2800 DEGs between and Normal samples, and then 7 overlapping genes were obtained. Importantly, ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ were determined as biomarkers with excellent diagnostic efficiency (AUC > 0.7). In PTC samples, ADK and TNFRSF10B were high-expressed while CYP7B1, FGFR2, and CPQ were low-expressed. Especially, the high-expression groups of ADK had a better prognosis, while the high-expression groups of CYP7B1, FGFR2, and CPQ had a worse prognosis. Afterward, immune infiltration analysis found that 16 immune cells had infiltration differences between the Tumor and Normal samples. Finally, transcription factor SP1 could regulate CYP7B1 and TNFRSF10B. Moreover, Navitoclax was a potential drug for PTC patients. Conclusion Overall, we described 5 biomarkers associated with adverse prognosis of PTC, including ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ. All these biomarkers were involved in succinate metabolism and m6A modification of RNA. This set of biomarkers should be explored further for their diagnostic value in PTC. Investigations into the mechanistic role of alteration of succinate metabolism and m6A modification of RNA pathways in the pathophysiology of PTC are warranted.

Objective To explore the epidemiological characteristics of voluntary blood donors with enzyme-linked immuno-sorbent assay (ELISA) negative and nucleic acid testing (NAT) positive in Hainan from 2012 to 2022, so as to provide reference for developing rational blood screening strategies. Methods The screening results for transfusion-transmitted disease markers in 1 161 042 blood samples in Hainan from 2012 to 2022 were retrospectively analyzed. All samples have been measured twice by ELISA and once by NAT. Statistical methods were used to analyze the proportion of ELISA negative and NAT positive (ELISA-/NAT+ ) among voluntary blood donors and its relation with factors including gender, age, ethnicity and region. Results Among the voluntary blood donors in Hainan from 2012 to 2022, the overall proportion of ELISA-/NAT+ was 0.19% (2 151/1 161 042), and the difference was statistically significant (P

Abstract Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I–III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p

Abstract Background The lack of professional identity can impede the transition from nursing students to qualified nurses and exacerbate the shortage of health care professionals. Personality is important to resilience-building and professional identity development in nursing students. However, the associations among personality, resilience, and professional identity are less explored. The study aims to identify latent subtypes of personality, to evaluate the mediating role of resilience between personality and professional identity in nursing students, and to provide practical guidance for educators’ subsequent interventions with nursing students’ professional identity. Methods 1397 nursing students were recruited from Be Resilient to Nursing Career (BRNC) between October 2020 and April 2022 by cluster sampling from 4 universities in China. NEO Five-Factor Inventory, 10-item Connor-Davidson Resilience Scale, and Professional Identity Questionnaire for Undergraduate Students were administered. Analyses of latent profiles and mediations were performed. Results Three latent personality types were identified: Over-sensitivity (35.4%), Ordinary (53.8%), and Flexibility (10.8%). Nursing role model was found to be a significant indicator of personality (Ordinary as ref, Over-sensitivity: OR = 0.73, 95% CI: 0.57–0.93, P = 0.010; Flexibility: OR = 1.85, 95% CI: 1.29–2.65, P = 0.001). The association between personality portraits and professional identity were significantly mediated by resilience (P

Abstract Background Pedicle screw instrument surgeries can result in the development of aortic pseudoaneurysm, which is a rare yet potentially severe complication; therefore, the purpose of this work is to describe the case of pseudoaneurysm of the thoracic aorta caused by the severe migration of a pedicle screw after surgery. Case presentation We herein report a patient who underwent endovascular repair for the pseudoaneurysm of the descending thoracic aorta following thoracic vertebral fixation surgery. A 28–80 mm covered stent was initially inserted through the right femoral artery, and intraoperative aortography revealed a minor extravasation of contrast material. Subsequently, an additional 28–140 mm covered stent was implanted. The patient recovered well during the 8-year follow-up period. Conclusions Vascular complications resulting from spinal surgery are severe and rare, necessitating early diagnosis and intervention.

Objective The clinical characteristics and prognosis of primary epithelial-myoepithelial carcinoma of salivary gland (EMC-SG) have not been defined well due to its rarity. The purpose of this study is to assess the proportion of EMC-SG among salivary gland cancers, describe the clinicopathological features and prognosis of this disease, further analyze the factors associated with EMC-SG survival, and establish individual survival-predicting models. Methods Data on patients diagnosed with salivary gland malignancy between 2000 and 2020 were collected from the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method and log-rank test were employed to estimate survival of EMC-SG patients. Univariable and multivariable Cox proportional hazards models were developed to determine the EMC-SG survival-associated factors. Furthermore, EMC-SG nomograms were constructed. Results A total of 15 212 patients with salivary gland malignancy were identified. Of these, 310 cases were diagnosed with EMC-SG, representing a prevalence of 2.03% (95%CI 1.82%-2.28%). The overall survival (OS) rates for all 310 EMC-SG patients at 2-year, 5-year, and 10-year were 92.43%, 84.85%, and 73.39%, respectively. Age, primary site, and T stage were independent prognostic factors for OS, while pathological grade and the use of surgery were independent prognostic factors for cancer-specific survival (CSS). The concordance index (C-index) for the OS- and CSS-specific nomograms was 0.72 (95%CI 0.64-0.80) and 0.77 (95%CI 0.67-0.87), respectively. The calibration curve and receiver operating characteristic analysis demonstrated that the predicted values aligned well with the actual observations. Decision curve analysis indicated the superiority of the nomograms over the traditional Tumor Node Metastasis staging system. Conclusions This study represents the largest cohort of EMC-SG patients used to investigate the characteristics and prognosis of this disease. EMC-SG patients often have a less aggressive course and favorable prognosis. The established nomograms provide a useful tool for clinicians to predict patient outcomes, and can assist in customizing the counseling approach for this rare disease.

Keratitis induced by Pseudomonas aeruginosa (P. aeruginosa) is an acute and serious corneal inflammation. As a family of gene regulators, miRNAs play a crucial role in modulating host response after microbial invasion. However, their functions in P. aeruginosa keratitis remain largely unclear. In the present study, we demonstrated that miR-155 expression was significantly increased in macrophages and corneal tissue after P. aeruginosa infection. In vivo studies demonstrated that mice with miR-155 knockdown displayed more resistance to P. aeruginosa keratitis, with a lower bacterial burden. In addition, in vitro and in vivo studies indicated that miR-155 enhanced apoptosis of macrophages after P. aeruginosa infection, and resulted in a susceptible phenotype of P. aeruginosa keratitis. Moreover, miR-155 induced apoptosis through reducing activation of PI3K-Akt signaling pathway. Our data provided evidence of miR-155 mediated apoptosis of macrophage in P. aeruginosa keratitis, which may be an underlying target for the therapy of P. aeruginosa keratitis and other infectious diseases.

Biosynthesis of atypical angucyclines involves unique oxidative B-ring cleavage and rearrangement reactions, which are catalyzed by AlpJ-family oxygenases, including AlpJ, JadG, and GilOII. Prior investigations established the essential requirement for FADH2/FMNH2 as cofactors when utilizing the quinone intermediate dehydrorabelomycin as a substrate. In this study, we unveil a previously unrecognized facet of these enzymes as cofactor-independent oxygenases when employing the hydroquinone intermediate CR1 as a substrate. The enzymes autonomously drive oxidative ring cleavage and rearrangement reactions of CR1, yielding products identical to those observed in cofactor-dependent reactions of AlpJ-family oxygenases. Furthermore, the AlpJ- and JadG-catalyzed reactions of CR1 could be quenched by superoxide dismutase, supporting a catalytic mechanism wherein the substrate CR1 reductively activates molecular oxygen, generating a substrate radical and the superoxide anion O2•−. Our findings illuminate a substrate-controlled catalytic mechanism of AlpJ-family oxygenases, expanding the realm of cofactor-independent oxygenases. Notably, AlpJ-family oxygenases stand as a pioneering example of enzymes capable of catalyzing oxidative reactions in either an FADH2/FMNH2-dependent or cofactor-independent manner.

Abstract Interplay between innate and adaptive immune cells is important for the antitumor immune response. However, the tumor microenvironment may turn immune suppressive, and tumor associated macrophages are playing a role in this transition. Here, we show that CD276, expressed on tumor-associated macrophages (TAM), play a role in diminishing the immune response against tumors. Using a model of tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in BLCA male mice we show that genetic ablation of CD276 in TAMs blocks efferocytosis and enhances the expression of the major histocompatibility complex class II (MHCII) of TAMs. This in turn increases CD4 + and cytotoxic CD8 + T cell infiltration of the tumor. Combined single cell RNA sequencing and functional experiments reveal that CD276 activates the lysosomal signaling pathway and the transcription factor JUN to regulate the expression of AXL and MerTK, resulting in enhanced efferocytosis in TAMs. Proving the principle, we show that simultaneous blockade of CD276 and PD-1 restrain tumor growth better than any of the components as a single intervention. Taken together, our study supports a role for CD276 in efferocytosis by TAMs, which is potentially targetable for combination immune therapy.

Abstract Background Lymphatic metastasis is the major challenge in the treatment of penile cancer. The prognosis of individuals with lymphatic metastasis is extremely poor. Therefore, early identification of disease progression and lymphatic metastasis is an urgent task for researchers in penile cancer worldwide. Methods In this study, using single‐cell RNA sequencing, an immune landscape was established for the cancer ecosystem based on 46,861 cells from six patients with penile cancer (four with lymphatic metastasis [stage IV] and two without lymphatic metastasis [stage I]). Using bulk RNA sequencing, the discrepancy between the cancers and their respective metastatic lymph nodes was depicted based on seven patients with penile cancer. Results The interaction between epithelial cells, fibroblasts, and endothelial cells, and the functional cooperation among invasion, epithelial‐mesenchymal transition, and angiogenesis were found to be important landscapes in the penile cancer ecosystem, playing important roles in progression of cancer and lymph node metastasis. Conclusions This study is the first to investigate the altered tumor microenvironment heterogeneity of penile cancer as it evolves from non‐lymphatic to lymphatic metastasis and provides insights into the mechanisms underlying malignant progression, the premetastatic niche, and lymphatic metastasis in penile cancer.

Penile cancer is a rare malignant tumor of the male urinary system. The treatment benefit of standard first-line chemotherapy is not ideal for patients with locally advanced or metastatic lymph nodes. Immunotherapy has brought new treatment strategies and opportunities for patients with penile cancer. At present, clinical studies on immunotherapy for penile cancer have been reported, and the results show that it is effective but not conclusive. With the development of immunotherapy and the progress of molecular research technology, we can better screen the immunotherapy response population and explore new combination treatment regimens to evaluate the best combination regimen and obtain the optimal treatment options, which is also an important research direction for the immunotherapy of penile cancer in the future.

Abstract Introduction Penile cancer (PC) is a lethal malignancy with no effective prognostic biomarker. We aim to investigate associations between trajectories of squamous cell carcinoma antigen (SCC‐A) and patient outcomes after chemotherapy based on paclitaxel, ifosfamid, and cisplatin (TIP) regimen. Methods Consecutive AJCC staging III/IV PC patients who received TIP chemotherapy and repeated SCC‐A measurements in 2014–2022 were analyzed. Latent class growth mixed (LCGM) models were employed to characterize patients' serum SCC‐A trajectories. Patient survival, and clinical and pathological tumor responses were compared. Inverse probability treatment weighting was used to adjust confounding factors. Results Eighty patients were included. LCGM models identified two distinct trajectories of SCC‐A: low‐stable (40%; n = 32) and high‐decline (60%; n = 48). Overall survival (HR [95% CI]: 3.60 [1.23–10.53], p = 0.019), progression‐free survival (HR [95% CI]: 11.33 [3.19–40.3], p

The interaction between microplastics (MPs) and cadmium (Cd) poses a threat to agricultural soil environments, and their effects on plant growth and rhizosphere microbial community functions are not yet clear. In this study, energy sorghum was used as a test plant to investigate the effects of two types of MPs, polystyrene (PS) and polyethylene (PE), at different particle sizes (13 μm, 550 μm) and concentrations (0.1%, 1% w/w), and Cd, as well as their interactions, on the growth of sorghum in a soil-cultivation pot experiment. The results showed that the combined effects of MP and Cd pollution on the dry weight and Cd accumulation rate in sorghum varied depending on the type, concentration, and particle size of the MPs, with an overall trend of increasing stress from combined pollution with increasing Cd content and accumulation. High-throughput sequencing analysis revealed that combined MP and Cd pollution increased bacterial diversity, and the most significant increase was observed in the abundance-based coverage estimator (ACE), Shannon, and Sobs indices in the 13 μm 1% PS+Cd treatment group. Metagenomic analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed that 19 groups of metabolic pathways, including microbial metabolism and methane metabolism, differed significantly under combined MP and Cd pollution. Hierarchical clustering results indicated that Cd treatment and combined MP and Cd treatment affected the abundances of sorghum rhizosphere soil nitrogen (N) and phosphorus (P) cycling genes and that the type of MP present was an important factor affecting N and P cycling genes. The results of this study provide a basis for exploring the toxic effects of combined MP and Cd pollution and for conducting soil environmental risk assessments.

Obesity is a major risk factor of hypertension, therefore quantifying the contribution of obesity to hypertension is necessary. The current study aimed to investigate the changes in population-attributable fractions (PAFs) of hypertension associated with general obesity and abdominal obesity over the recent 2 decades among the US population, as well as important sub-populations. This report was performed based on national-level cross-sectional data for 46,535 adults aged 18 years and older and 20,745 children aged 8–17 from the US National Health and Nutrition Examination Survey 1999–2018. The PAFs of hypertension due to general obesity and abdominal obesity were calculated by sex, race/ethnicity, and survey year. The linear regression analysis was used to evaluate the secular trends of PAFs over the years. The prevalence of general obesity and abdominal obesity presented significantly increasing trends during the past 2 decades in the US. The PAFs of hypertension due to general obesity increased steadily from 11.9 % to 15.1 % in women with a slope of 0.38 % (95 % CI: 0.31 – 0.45 %) and from 8.4 % to 13.4 % in men with a slope of 0.46 % (95 % CI: 0.36 – 0.56 %). Similar increasing trends were also observed for the PAFs due to abdominal obesity in both women and men. Additionally, there were significantly different trends of PAFs in various races/ethnicities. Over the past 2 decades, the contributions of obesity to hypertension were gradually rising among US population, which emphasizes the importance of controlling weight to further reduce the burden of hypertension.

The quality of water in urban parks is closely related to people’s daily lives, but the pollution caused by microplastics in park water and sediments has not been comprehensively studied. Therefore, eight typical parks in the urban area of Changsha, China, were selected, and Raman spectroscopy was used to explore the spatial distributions and compositions of the microplastics in the water and sediments, analyze their influencing factors, and evaluate their environmental risks. The results showed that the abundances of surface water microplastics in all parks ranged from 150 to 525 n L−1, and the abundances of sediment microplastics ranged from 120 to 585 n kg−1. The microplastics in the surface water included polyethylene terephthalate (PET), chlorinated polyethylene (CPE), and fluororubber (FLU), while those in the sediments included polyvinyl chloride (PVC), wp-acrylate copolymer (ACR), and CPE. Regression analyses revealed significant positive correlations between human activities and the abundances of microplastics in the parks. Among them, the correlations of population, industrial discharge and domestic wastewater discharge with the abundance of microplastics in park water were the strongest. However, the correlations of car flow and tourists with the abundance of microplastics in park water were the weakest. Based on the potential ecological risk indices (PERI) classification assessment method, the levels of microplastics in the waters and sediments of the eight parks were all within the II-level risk zone (53–8,549), among which the risk indices for Meixi Lake and Yudai Lake were within the IV risk zone (1,365–8,549), which may have been caused by the high population density near the park. This study provides new insights into the characteristics of microplastics in urban park water and sediment.

BackgroundTheories propose that brief, mobile, self-guided mindfulness ecological momentary interventions (MEMIs) could enhance emotion regulation (ER) and self-compassion. Such changes are posited to be mechanisms of change. However, rigorous tests of these theories have not been conducted. ObjectiveIn this assessor-blinded, parallel-group randomized controlled trial, we aimed to test these theories in social anxiety disorder (SAD). MethodsParticipants with SAD (defined as having a prerandomization cut-off score ≥20 on the Social Phobia Inventory self-report) were randomized to a 14-day fully self-guided MEMI (96/191, 50.3%) or self-monitoring app (95/191, 49.7%) arm. They completed web-based self-reports of 6 clinical outcome measures at prerandomization, 15-day postintervention (administered the day after the intervention ended), and 1-month follow-up time points. ER and self-compassion were assessed at preintervention and 7-day midintervention time points. Multilevel modeling determined the efficacy of MEMI on ER and self-compassion domains from pretrial to midintervention time points. Bootstrapped parallel multilevel mediation analysis examined the mediating role of pretrial to midintervention ER and self-compassion domains on the efficacy of MEMI on 6 clinical outcomes. ResultsParticipants demonstrated strong compliance, with 78% (149/191) engaging in at least 80% of the MEMI and self-monitoring prompts. MEMI was more efficacious than the self-monitoring app in decreasing ER goal–directed behavior difficulties (between-group Cohen d=−0.24) and lack of emotional clarity (Cohen d=0.16) and increasing self-compassion social connectedness (Cohen d=0.19), nonidentification with emotions (Cohen d=0.16), and self-kindness (Cohen d=0.19) from pretrial to midintervention time points. The within-group effect sizes from pretrial to midintervention were larger in the MEMI arm than in the self-monitoring app arm (ER goal–directed behavior difficulties: Cohen d=−0.73 vs −0.29, lack of emotional clarity: Cohen d=−0.39 vs −0.21, self-compassion domains of social connectedness: Cohen d=0.45 vs 0.19, nonidentification with emotions: Cohen d=0.63 vs 0.48, and self-kindness: Cohen d=0.36 vs 0.10). Self-monitoring, but not MEMI, alleviated ER emotional awareness issues (between-group Cohen d=0.11 and within-group: Cohen d=−0.29 vs −0.13) and reduced self-compassion acknowledging shared human struggles (between-group Cohen d=0.26 and within-group: Cohen d=−0.23 vs 0.13). No ER and self-compassion domains were mediators of the effect of MEMI on SAD symptoms (P=.07-

Summary: Emerging studies have demonstrated the link between RNA modifications and various cancers, while the predictive value and functional mechanisms of RNA modification-related genes (RMGs) in esophageal squamous cell carcinoma (ESCC) remain unclear. Here we established a prognostic signature for ESCC based on five RMGs. The analysis of ESCC clinical samples further verified the prognostic power of the prognostic signature. Moreover, we found that the knockdown of NSUN6 promotes ESCC progression in vitro and in vivo, whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells. Mechanically, NSUN6 mediated tRNA m5C modifications selectively enhance the translation efficiency of CDH1 mRNA in a codon dependent manner. Rescue assays revealed that E-cadherin is an essential downstream target that mediates NSUN6’s function in the regulation of ESCC progression. These findings offer additional insights into the link between ESCC and RMGs, as well as provide potential strategies for ESCC management and therapy.

Background: Lactylation is a significant post-translational modification bridging the gap between cancer epigenetics and metabolic reprogramming. However, the association between lactylation and prognosis, tumor microenvironment (TME), and response to drug therapy in various cancers remains unclear. Methods: First, the expression, prognostic value, and genetic and epigenetic alterations of lactylation genes were systematically explored in a pan-cancer manner. Lactylation scores were derived for each tumor using the single-sample gene set enrichment analysis (ssGSEA) algorithm. The correlation of lactylation scores with clinical features, prognosis, and TME was assessed by integrating multiple computational methods. In addition, GSE135222 data was used to assess the efficacy of lactylation scores in predicting immunotherapy outcomes. The expression of lactylation genes in breast cancers and gliomas were verified by RNA-sequencing. Results: Lactylation genes were significantly upregulated in most cancer types. CREBBP and EP300 exhibited high mutation rates in pan-cancer analysis. The prognostic impact of the lactylation score varied by tumor type, and lactylation score was a protective factor for KIRC, ACC, READ, LGG, and UVM, and a risk factor for CHOL, DLBC, LAML, and OV. In addition, a high lactylation score was associated with cold TME. The infiltration levels of CD8+ T, γδT, natural killer T cell (NKT), and NK cells were lower in tumors with higher lactylation scores. Finally, immunotherapy efficacy was worse in patients with high lactylation scores than other types. Conclusion: Lactylation genes are involved in malignancy formation. Lactylation score serves as a promising biomarker for predicting patient prognosis and immunotherapy efficacy.

Introduction and Objectives: Accumulating evidence has supported that mild elevated total bilirubin exerts antioxidant and anti-inflammatory properties in multiple metabolic diseases. We aimed to explore the association of circulating total bilirubin concentration with non-alcoholic fatty liver disease (NAFLD) risk and all-cause mortality and examine the potential nonlinear relationships between them. Material and Methods: We used nationally representative data from the National Health and Nutrition Examination Survey (NHANES). NAFLD was assessed using the fatty liver index (FLI) and United States fatty liver index (USFLI), respectively. Results: A total of 35 912 and 17 329 participants were included in FLI-NAFLD (case with NAFLD was diagnosed by FLI) and USFLI-NAFLD (case with NAFLD was diagnosed by USFLI) groups, respectively. The mean age of total population was 46.25 years, and 48.51% were male. Compared to participants with lowest quintile of total bilirubin concentration, those with highest quintile had lower risk of NAFLD in both FLI-NAFLD (OR: 0.48, 95% CI: 0.40, 0.59) and USFLI-NAFLD (OR: 0.55, 95% CI: 0.43, 0.70) groups. Compared to participants with lowest quintile of total bilirubin concentration, the association between total bilirubin concentration and all-cause mortality was not significant among those with highest quintile of total bilirubin concentration (HR: 0.89, 95% CI: 0.66, 1.20). The restricted spline curves showed the nonlinear U-shaped association of total bilirubin concentration with NAFLD risk and all-cause mortality. The segmented linear regression analysis showed negative associations between total bilirubin concentration and risk of NAFLD in both FLI-NAFLD (OR: 0.94, 95% CI: 0.93, 0.95) and USFLI-NAFLD (OR: 0.95, 95% CI: 0.93, 0.96) groups when total bilirubin concentration was below the turning point (FLI-NAFLD: 18.81 μmol/L; USFLI-NAFLD: 15.39 μmol/L) and these associations were not significant when total bilirubin concentration was higher than the turning point. Furthermore, all-cause mortality decreased (OR: 0.97, 95%CI: 0.95, 1.00) with increased total bilirubin concentration up to the turning point (11.97 μmol/L), and then all-cause mortality increased with increasing total bilirubin concentration (OR: 1.03, 95%CI: 1.02, 1.04). Conclusions: We found that higher circulating total bilirubin concentration within the physiological range was associated with decreased risk of NAFLD and all-cause mortality among NAFLD patients.

In this work, we demonstrated a novel, sensitive and effective fluorescent naringin (NRG) and naringenin (NRGe) detection method using polymethionine nanoparticles (PMNPs) as a fluorescent nanoprobe. The PMNPs were first synthesized by autopolymerization of methionine at 90 °C when trace copper ions existed. The as-prepared PMNPs were thoroughly characterized by transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), gel permeation chromatograph (GPC), nuclear magnetic resonance spectroscopy (NMR), transient and steady-state fluorescence and UV–Vis absorption spectroscopy. The quenching mechanism was attributed to the inner filter effect (IFE). Moreover, the developed assay was used successfully to detect NRG and NRGe in real samples of citrus fruits, illustrating that this detection method has great potential application in the field of citrus fruits analysis.

Tight junctional complexes (TJCs) between cerebral microvascular endothelial cells (CMECs) are essential parts of the blood–brain barrier (BBB), whose regulation closely correlates to the BBB’s integrity and function. hCMEC/D3 is the typical cell line used to imitate and investigate the barrier function of the BBB via the construction of an in vitro model. This study aims to investigate the protective effect of the deep-sea-derived fibrinolytic compound FGFC1 against H2O2-induced dysfunction of TJCs and to elucidate the underlying mechanism. The barrier function was shown to decline following exposure to 1 mM H2O2 in an in vitro model of hCMEC/D3 cells, with a decreasing temperature-corrected transendothelial electrical resistance (tcTEER) value. The decrease in the tcTEER value was significantly inhibited by 80 or 100 µM FGFC1, which suggested it efficiently protected the barrier integrity, allowing it to maintain its function against the H2O2-induced dysfunction. According to immunofluorescence microscopy (IFM) and quantitative real-time polymerase chain reaction (qRT-PCR), compared to the H2O2-treated group, 80~100 µM FGFC1 enhanced the expression of claudin-5 (CLDN-5) and VE-cadherin (VE-cad). And this enhancement was indicated to be mainly achieved by both up-regulation of CLDN-5 and inhibition of the down-regulation by H2O2 of VE-cad at the transcriptional level. Supported by FGFC1’s molecular docking to these proteins with reasonable binding energy, FGFC1 was proved to exert a positive effect on TJCs’ barrier function in hCMEC/D3 cells via targeting CLDN-5 and VE-cad. This is the first report on the protection against H2O2-induced barrier dysfunction by FGFC1 in addition to its thrombolytic effect. With CLDN-5 and VE-cad as the potential target proteins of FGFC1, this study provides evidence at the cellular and molecular levels for FGFC1’s reducing the risk of bleeding transformation following its application in thrombolytic therapy for cerebral thrombosis.

The Hosoya index is an important topological index in graph theory, which is defined as the total number of s-matchings, denoted as m(G,s), in a graph G. Therefore, computing the number of s-matchings for various molecular structures holds significant importance. By applying the concept of symmetry, defining the s-matching vector of the graph with a specified edge, using the transfer matrix, and iteratively applying two recursive formulas to derive the reduction formula, we compute the number of s-matchings of cyclooctatetraene chains.

The application of phosphorus-solubilizing bacteria is an effective method for increasing the available phosphorus content and inhibiting wheat uptake of heavy metals. However, further research is needed on the mechanism by which phosphorus-solubilizing bacteria inhibit cadmium (Cd) uptake in wheat roots and its impact on the expression of root-related genes. Here, the effects of strain Klebsiella aerogenes M2 on Cd absorption in wheat and the expression of root-related Cd detoxification and immobilization genes were determined. Compared with the control, strain M2 reduced (64.1–64.6%) Cd uptake by wheat roots. Cd fluorescence staining revealed that strain M2 blocked the entry of exogenous Cd into the root interior and enhanced the immobilization of Cd by cell walls. Forty-seven genes related to Cd detoxification, including genes encoding peroxidase, chalcone synthase, and naringenin 3-dioxygenase, were upregulated in the Cd+M2 treatment. Strain M2 enhanced the Cd resistance and detoxification activity of wheat roots through the regulation of flavonoid biosynthesis and antioxidant enzyme activity. Moreover, strain M2 regulated the expression of genes related to phenylalanine metabolism and the MAPK signaling pathway to enhance Cd immobilization in roots. These results provide a theoretical basis for the use of phosphorus-solubilizing bacteria to remediate Cd-contaminated fields and reduce Cd uptake in wheat.

Obesity is a global health challenge that has received increasing attention in contemporary research. The gut microbiota has been implicated in the development of obesity, primarily through its involvement in regulating various host metabolic processes. Recent research suggests that epigenetic modifications may serve as crucial pathways through which the gut microbiota and its metabolites contribute to the pathogenesis of obesity and other metabolic disorders. Hence, understanding the interplay between gut microbiota and epigenetic mechanisms is crucial for elucidating the impact of obesity on the host. This review primarily focuses on the understanding of the relationship between the gut microbiota and its metabolites with epigenetic mechanisms in several obesity-related pathogenic mechanisms, including energy dysregulation, metabolic inflammation, and maternal inheritance. These findings could serve as novel therapeutic targets for probiotics, prebiotics, and fecal microbiota transplantation tools in treating metabolic disruptions. It may also aid in developing therapeutic strategies that modulate the gut microbiota, thereby regulating the metabolic characteristics of obesity.

Angiotensin-converting enzyme 2 (ACE2) is a major cell entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The induction of ACE2 expression may serve as a strategy by SARS-CoV-2 to facilitate its propagation. However, the regulatory mechanisms of ACE2 expression after viral infection remain largely unknown. Using 45 different luciferase reporters, the transcription factors SP1 and HNF4α were found to positively and negatively regulate ACE2 expression, respectively, at the transcriptional level in human lung epithelial cells (HPAEpiCs). SARS-CoV-2 infection increased the transcriptional activity of SP1 while inhibiting that of HNF4α. The PI3K/AKT signaling pathway, activated by SARS-CoV-2 infection, served as a crucial regulatory node, inducing ACE2 expression by enhancing SP1 phosphorylation—a marker of its activity—and reducing the nuclear localization of HNF4α. However, colchicine treatment inhibited the PI3K/AKT signaling pathway, thereby suppressing ACE2 expression. In Syrian hamsters (Mesocricetus auratus) infected with SARS-CoV-2, inhibition of SP1 by either mithramycin A or colchicine resulted in reduced viral replication and tissue injury. In summary, our study uncovers a novel function of SP1 in the regulation of ACE2 expression and identifies SP1 as a potential target to reduce SARS-CoV-2 infection.

Background & Aims: There is limited information on how the liver-to-gut axis contributes to alcohol-associated liver disease (AALD). We previously identified that high-mobility group box-1 (HMGB1) undergoes oxidation in hepatocytes and demonstrated elevated serum levels of oxidized HMGB1 ([O] HMGB1) in alcoholic patients. Since interleukin-1 beta (IL-1B) increases in AALD, we hypothesized hepatocyte-derived [O] HMGB1 could interact with IL-1B to activate a pro-inflammatory program that, besides being detrimental to the liver, drives intestinal barrier dysfunction. Results: Alcohol-fed RageΔMye mice exhibited decreased nuclear factor kappa B signaling, a pro-inflammatory signature, and reduced total intestinal permeability, resulting in protection from AALD. In addition, [O] HMGB1 bound and signaled through the receptor for advanced-glycation end-products (RAGE) in myeloid cells, driving hepatic inflammation, intestinal permeability, and increased portal blood lipopolysaccharide in AALD. We identified that [O] HMGB1 formed a complex with IL-1B, which was found in the livers of patients with acute alcoholic hepatitis and mice with AALD. This complex originated from the liver, because it was absent in the intestine when hepatocytes did not produce [O] HMGB1. Mechanistically, the complex bound RAGE in Kupffer cells and macrophages induced a pro-inflammatory program. Moreover, it bound RAGE in intestinal macrophages and epithelial cells, leading to intestinal inflammation, altered intestinal epithelial cell tight junction protein expression, increased intestinal permeability, and elevated portal blood lipopolysaccharide, enhancing AALD pathogenesis. Conclusions: We identified a protein complex of liver origin that amplifies the pro-inflammatory feedback loop in AALD; therefore, targeting this complex could have significant therapeutic potential.

Background. Cerebral ischemia–reperfusion injury is a common complication of ischemic stroke that affects the prognosis of patients with ischemic stroke. The lipid-soluble diterpene Tanshinone IIA, which was isolated from Salvia miltiorrhiza, has been indicated to reduce cerebral ischemic injury. In this study, we investigated the molecular mechanism of Tanshinone IIA in alleviating reperfusion-induced brain injury. Methods. Middle cerebral artery occlusion animal models were established, and neurological scores, tetrazolium chloride staining, brain volume quantification, wet and dry brain water content measurement, Nissl staining, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription–quantitative polymerase chain reaction were performed. The viability of cells was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assays, while cell damage was measured by lactate dehydrogenase release in the in vitro oxygen glucose deprivation model. In addition, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription–quantitative polymerase chain reaction were used to evaluate the therapeutic effect of Tanshinone IIA on ischemia/reperfusion (I/R) induced brain injury, as well as its effects on the inflammatory response and neuronal apoptosis, in vivo and in vitro. Furthermore, this study validated the targeting relationship between miR-124-5p and FoxO1 using a dual luciferase assay. Finally, we examined the role of Tanshinone IIA in brain injury from a molecular perspective by inhibiting miR-124-5p or increasing FoxO1 levels. Results. After treatment with Tanshinone IIA in middle cerebral artery occlusion–reperfusion (MCAO/R) rats, the volume of cerebral infarction was reduced, the water content of the brain was decreased, the nerve function of the rats was significantly improved, and the cell damage was significantly reduced. In addition, Tanshinone IIA effectively inhibited the I/R-induced inflammatory response and neuronal apoptosis, that is, it inhibited the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, decreased the expression of apoptotic protein Bax and Cleaved-caspase-3, and promoted the expression of antiapoptotic protein Bcl-2. In vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, Tanshinone IIA also inhibited the expression of inflammatory factors in neuronal cells and inhibited the occurrence of neuronal apoptosis. In addition, Tanshinone IIA promoted the expression of miR-124-5p. Transfection of miR-124-5p mimic has the same therapeutic effect as Tanshinone IIA and positive therapeutic effect on OGD cells, while transfection of miR-124-5p inhibitor has the opposite effect. The targeting of miR-124-5p negatively regulates FoxO1 expression. Inhibition of miR-124-5p or overexpression of FoxO1 can weaken the inhibitory effect of Tanshinone IIA on brain injury induced by I/R, while inhibition of miR-124-5p and overexpression of FoxO1 can further weaken the effect of Tanshinone IIA. Conclusion. Tanshinone IIA alleviates ischemic–reperfusion brain injury by inhibiting neuroinflammation through the miR-124-5p/FoxO1 axis. This finding provides a theoretical basis for mechanistic research on cerebral ischemia–reperfusion injury.

Quantitative evaluation of the effects of diverse greenhouse vegetable production systems (GVPS) on vegetable yield, soil water consumption, and nitrogen (N) fates could provide a scientific basis for identifying optimum water and fertilizer management practices for GVPS. This research was conducted from 2013 to 2015 in a greenhouse vegetable field in Quzhou County, North China. Three production systems were designed: conventional (CON), integrated (INT), and organic (ORG) systems. The WHCNS-Veg model was employed for simulating vegetable growth, water dynamics, and fates of N, as well as water and N use efficiencies (WUE and NUE) for four continuous growing seasons. The simulation results revealed that nitrate leaching and gaseous N emissions constituted the predominant N loss within GVPS, which separately accounted for 11.5–59.4% and 6.0–21.1% of the N outputs. The order of vegetable yield, N uptake, WUE, and NUE under different production systems was ORG > INT > CON, while the order of nitrate leaching and gaseous N loss was CON > INT > ORG. Compared to CON, ORG exhibited a significant increase in yield, N uptake, WUE, and NUE by 24.6%, 24.2%, 26.1%, and 89.7%, respectively, alongside notable reductions in nitrate leaching and gaseous N loss by 67.7% and 63.2%, respectively. The ORG system should be recommended to local farmers.

The green and efficient remediation of soil cadmium (Cd) is an urgent task, and plant-microbial joint remediation has become a research hotspot due to its advantages. High-throughput sequencing and metabolomics have technical advantages in analyzing the microbiological mechanism of plant growth-promoting bacteria in improving phytoremediation of soil heavy metal pollution. In this experiment, a pot trial was conducted to investigate the effects of inoculating the plant growth-promoting bacterium Enterobacter sp. VY on the growth and Cd remediation efficiency of the energy plant Hybrid pennisetum. The test strain VY-1 was analyzed using high-throughput sequencing and metabolomics to assess its effects on microbial community composition and metabolic function. The results demonstrated that Enterobacter sp. VY-1 effectively mitigated Cd stress on Hybrid pennisetum, resulting in increased plant biomass, Cd accumulation, and translocation factor, thereby enhancing phytoremediation efficiency. Analysis of soil physical-chemical properties revealed that strain VY-1 could increase soil total nitrogen, total phosphorus, available phosphorus, and available potassium content. Principal coordinate analysis (PCoA) indicated that strain VY-1 significantly influenced bacterial community composition, with Proteobacteria, Firmicutes, Chloroflexi, among others, being the main differential taxa. Redundancy analysis (RDA) revealed that available phosphorus, available potassium, and pH were the primary factors affecting bacterial communities. Partial Least Squares Discriminant Analysis (PLS-DA) demonstrated that strain VY-1 modulated the metabolite profile of Hybrid pennisetum rhizosphere soil, with 27 differential metabolites showing significant differences, including 19 up-regulated and eight down-regulated expressions. These differentially expressed metabolites were primarily involved in metabolism and environmental information processing, encompassing pathways such as glutamine and glutamate metabolism, α-linolenic acid metabolism, pyrimidine metabolism, and purine metabolism. This study utilized 16S rRNA high-throughput sequencing and metabolomics technology to investigate the impact of the plant growth-promoting bacterium Enterobacter sp. VY-1 on the growth and Cd enrichment of Hybrid pennisetum, providing insights into the regulatory role of plant growth-promoting bacteria in microbial community structure and metabolic function, thereby improving the microbiological mechanisms of phytoremediation.

B0 field inhomogeneity is a long-lasting issue for Cardiac MRI (CMR) in high-field (3T and above) scanners. The inhomogeneous B0 fields can lead to corrupted image quality, prolonged scan time, and false diagnosis. B0 shimming is the most straightforward way to improve the B0 homogeneity. However, today’s standard cardiac shimming protocol requires manual selection of a shim volume, which often falsely includes regions with large B0 deviation (e.g., liver, fat, and chest wall). The flawed shim field compromises the reliability of high-field CMR protocols, which significantly reduces the scan efficiency and hinders its wider clinical adoption. This study aims to develop a dual-channel deep learning model that can reliably contour the cardiac region for B0 shim without human interaction and under variable imaging protocols. By utilizing both the magnitude and phase information, the model achieved a high segmentation accuracy in the B0 field maps compared to the conventional single-channel methods (Dice score: 2D-mag = 0.866, 3D-mag = 0.907, and 3D-mag-phase = 0.938, all p < 0.05). Furthermore, it shows better generalizability against the common variations in MRI imaging parameters and enables significantly improved B0 shim compared to the standard method (SD(B0Shim): Proposed = 15 ± 11% vs. Standard = 6 ± 12%, p < 0.05). The proposed autonomous model can boost the reliability of cardiac shimming at 3T and serve as the foundation for more reliable and efficient high-field CMR imaging in clinical routines.

Cloud computing-based online education has played a vital role in enabling uninterrupted learning during crises such as the COVID-19 pandemic. This study explored the key variables associated with cloud computing that can effectively support the operation of online education platforms. By analyzing real data from 63 online learning platforms, the study utilizes the unsupervised random forest (RF) method, ranking the importance of cloud computing-related variables using the Gini index and permutation importance and Boruta. The study's contributions include the application of innovative techniques such as Addcl1 and K-means clustering for data pre-processing, unsupervised RF dissimilarity calculated by partitioning around medoids (PAM) clustering and multidimensional scaling (MDS) plots, and the comparison of RF accuracy (98.4%) with other machine learning techniques using WEKA software. The results highlight variables such as public cloud, commercial sourcing, course number limitations, and synchronized tools as important factors in the successful implementation of cloud computing-based online learning platforms. The theoretical and practical implications of the study results can be used by researchers and practitioners to structure cloud computing-based online learning platforms that could successfully function for distance learning during crises like the COVID-19 pandemic.

Mutations modification enzymes including the tRNA N7-methylguanosine (m7G) methyltransferase complex component WDR4 were frequently found in patients with neural disorders, while the pathogenic mechanism and therapeutic intervention strategies are poorly explored. In this study, we revealed that patient-derived WDR4 mutation leads to temporal and cell-type-specific neural degeneration, and directly causes neural developmental disorders in mice. Mechanistically, WDR4 point mutation disrupts the interaction between WDR4 and METTL1 and accelerates METTL1 protein degradation. We further uncovered that impaired tRNA m7G modification caused by Wdr4 mutation decreases the mRNA translation of genes involved in mTOR pathway, leading to elevated endoplasmic reticulum stress markers, and increases neural cell apoptosis. Importantly, treatment with stress-attenuating drug Tauroursodeoxycholate (TUDCA) significantly decreases neural cell death and improves neural functions of the Wdr4 mutated mice. Moreover, adeno-associated virus mediated transduction of wild-type WDR4 restores METTL1 protein level and tRNA m7G modification in the mouse brain, and achieves long-lasting therapeutic effect in Wdr4 mutated mice. Most importantly, we further demonstrated that both TUDCA treatment and WDR4 restoration significantly improve the survival and functions of human iPSCs-derived neuron stem cells that harbor the patient's WDR4 mutation. Overall, our study uncovers molecular insights underlying WDR4 mutation in the pathogenesis of neural diseases and develops two promising therapeutic strategies for treatment of neural diseases caused by impaired tRNA modifications. [ABSTRACT FROM AUTHOR]

Conjugated polymers (CPs), which emit in the second near-infrared window (NIR-II, 1000–1700 nm), are used as biomaterials for NIR-II fluorescence imaging because of their adjustable photophysical properties and high optical stability. However, the fluorescence signal of conventional CPs is quenched in an aggregated state due to strong π–π stacking, which results in the closure of the radiation attenuation pathway. To solve this problem, the aggregation-induced emission effect is considered a reasonable strategy for enhancing the aggregative fluorescence of IR-II emitters. We herein report NIR-II conjugated polymers with typical AIE characteristics (αAIE > 3) by changing the side chain structure of receptor units and the conjugation degree of donors. Conjugated polymer nanoparticles (PoBVT NPs) exhibit outstanding performance in NIR-II fluorescence imaging (QY = 1.94%) and highly effective photothermal therapy (n = 45%). In vivo studies have shown that the location of tumors can be accurately obtained by NIR-II FL/NIR-II PA imaging, and there is a significant anti-tumor effect after laser irradiation. This work offers prospects for the design of multifunctional conjugated polymers for NIR-II FL/PA imaging to guide NIR-II PTT applications [ABSTRACT FROM AUTHOR]

Background: The high sensitivity of HBsAg quantitative tests has led to some challenges in the qualitative interpretation of weakly positive specimens. This study aimed to explore the clinical utility of neutralization confirmatory testing for specimens with low positive hepatitis B surface antigen (HBsAg). Methods: A retrospective analysis was conducted on outpatient and inpatient cases, from January 2021 to January 2022, at the Zhongshan City People's Hospital, Zhongshan. Confirmatory testing as well as enzyme-linked immunosorbent assay (ELISA) was applied to reanalyze 382 samples with low positive HBsAg detected by chemiluminescence microparticle immunoassay (CMIA). A retrospective analysis of hepatitis B serum markers, including eantigen, e-antibody, and core antibody patterns, was also performed. Results: When the HBsAg value ranged from 0.05 - 0.09 IU/mL, the positivity rate of the confirmatory testing was 34.5%. The HBsAg true positivity levels were all between 0.07 and 0.09. In the range of 0.10 - 0.49, the positivity rate of confirmatory testing was 96.1%. The three methods exhibited a high consistency, when testing samples with relatively high HBsAg values. A receiver operating characteristic (ROC) analysis showed that the optimal sensitivity and specificity were achieved at 0.14 IU/mL. For the HBV e-antigen-positive and negative groups, the positivity rate of confirmatory testing was 100% and 93.8%, with no statistical difference between them. Conclusions: For specimens with weakly positive, low-value HBsAg, particularly when the hepatitis B surface antigen level is less than 0.14 IU/mL, neutralization confirmatory testing can serve as a means for further confirmation. [ABSTRACT FROM AUTHOR]

This paper is about the unique spatial arrangement of the capital (Nanjing) and imperial mausoleum (Xiaoling) in fourteenth-century China. According to Confucian principles and traditional practices, the location of tombs should be separated from the space of the living for philosophical and emotional reasons. However, this convention was challenged by the Hongwu emperor (1368–1398), founder of the Ming dynasty (1368–1644), who built his own imperial mausoleum, Xiaoling, within the confines of the capital, an unprecedented act. According to primary sources—ritual texts, gazettes, tour books, and poetry—this innovative capital–mausoleum plan suggests an extension of the pattern by which the Hongwu emperor honored his ancestors through spatial arrangements and incorporated the imperial ancestors into dynasty-building. [ABSTRACT FROM AUTHOR]

Introduction: Disrupted in schizophrenia-1 (DISC1) is a scaffolding protein whose mutated form has been linked to schizophrenia, bipolar affective disorders, and recurrent major depression. DISC1 regulates multiple signaling pathways involved in neurite outgrowth and cortical development and binds directly to glycogen synthase kinase-3β (GSK-3β). Since ketamine activates GSK-3β, we examined the impact of ketamine on DISC1 and GSK-3β expression. Methods: Postnatal day 7 rat pups were treated with ketamine with and without the non-specific GSK-3β antagonist, lithium. Cleaved-caspase-3, GSK-3β and DISC1 levels were measured by immunoblots and DISC1 co-localization in neurons by immunofluorescence. Binding of DISC1 to GSK-3β was determined by co-immunoprecipitation. Neurite outgrowth was determined by measuring dendrite and axon length in primary neuronal cell cultures treated with ketamine and lithium. Results: Ketamine decreased DISC1 in a dose and time-dependent manner. This corresponded to decreases in phosphorylated GSK-3β, which implicates increased GSK-3β activity. Lithium significantly attenuated ketamine-induced decrease in DISC1 levels. Ketamine decreased co-immunoprecipitation of DISC1 with GSK-3β and axonal length. Conclusion: These findings confirmed that acute administration of ketamine decreases in DISC1 levels and axonal growth. Lithium reversed this effect. This interaction provides a link between DISC1 and ketamine-induced neurodegeneration. [ABSTRACT FROM AUTHOR]

Adopting Gilles Deleuze and Felix Guattari's formulations of the rhizome, this article will examine a dynamic that lies between the film Japón's (Carlos Reygadas, 2002) vernacular specificities, European modernist aesthetics and cosmopolitan spectatorship. The article aims to reveal that Japón, along with other contemporary slow films from around the world, has the potential to reify a deterritorialising and reterritorialising encounter that rethinks a Eurocentric genealogical reading of world cinema and challenges a capitalist code of filmmaking. [ABSTRACT FROM AUTHOR]

Background: Biological treatments are effective in the management of psoriasis. However, results in the real‑world setting may differ from clinical trials. Objectives: We aimed to evaluate the effectiveness of biological drugs among patients with psoriasis in Malaysia. Methods: This was a retrospective review of adult patients on biologics who were notified to the Malaysian Psoriasis Registry between 2011 and 2019. Univariate and multivariate logistic regression was performed to identify factors associated with response to treatment in terms of the Psoriasis Area and Severity Index (PASI) 75, PASI 90, and Dermatology Life Quality Index (DLQI) 0/1. Results: Of 130 patients, the most prescribed drug was ustekinumab (40.8%), followed by adalimumab (29.2%) and secukinumab (24.6%). Overall, the differences in the median PASI scores from baseline were −23.9 at 3–6 months, −25.8 at 12 months, and −27.8 at 3 years, while the difference in the median DLQI scores was −13.0 at 3–6 months. At 3–6 months, 57.6% achieved PASI‑75, 32.9% achieved PASI‑90, and 4.7% achieved PASI‑100. These responses were sustained at 12 months and 3 years. Adalimumab was the most effective treatment with 88.9% achieving PASI‑75, 77.8% PASI‑90, and 22.2% PASI‑100 at 3 years. However, secukinumab was more effective at achieving a PASI‑100 response at 3–6 months (9.1%). Chinese or Indian ethnicity, concurrent use of systemic therapy or phototherapy, comorbidities, and a longer duration of psoriasis were associated with poorer response. Conclusion: Biological treatments, particularly adalimumab and secukinumab, are effective in reducing disease severity and improving the quality of life of patients with psoriasis in Malaysia. [ABSTRACT FROM AUTHOR]