Nobiletin derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone, inhibits neuroinflammation through the inhibition of TLR4/MyD88/MAPK signaling pathways and STAT3 in microglia.

Objective: Microglia in the central nervous system regulate neuroinflammation that leads to a wide range of neuropathological alterations. The present study investigated the anti-neuroinflammatory properties of nobiletin (Nob) derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone (5-Ac-Nob), in lipopolysaccharide (LPS)-activated BV2 microglia.Materials and Methods: By using the MTT assay, Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), we determined the cell viability, the levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors (interleukin 1 beta; IL-1ß, interleukin 6; IL-6, tumor necrosis factor alpha; TNF-α and prostaglandin E2; PGE2) in LPS-stimulated BV2 microglia. Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) signaling pathway and signal transducer and activator of transcription 3 (STAT3) were measured by western blotting. Analysis of NO generation and mRNA of pro-inflammatory cytokines was confirmed in the zebrafish model.Results: 5-Ac-Nob reduced cell death, the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and pro-inflammatory factors in LPS-activated BV-2 microglial cells. TLR4-mediated MyD88/NF-κB and MAPK pathway (p38, ERK and JNK) after exposure to 5-Ac-Nob was also suppressed. Moreover, 5-Ac-Nob inhibited phosphorylated STAT3 proteins expression in LPS-induced BV-2 microglial cells. Furthermore, we confirmed that 5-Ac-Nob decreased LPS-induced NO generation and mRNA of pro-inflammatory cytokines in the zebrafish model.Conclusions: Our findings suggest that 5-Ac-Nob represses neuroinflammatory responses by inhibiting TLR4-mediated signaling pathway and STAT3. As a result of these findings, 5-Ac-Nob has potential as an anti-inflammatory agent against microglia-mediated neuroinflammatory disorders.

Mesenchymal stem cells and their derived exosomes for the treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection typically presents with fever and respiratory symptoms, which can progress to severe respiratory distress syndrome and multiple organ failure. In severe cases, these complications may even lead to death. One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response. Therefore, suppressing the overactive immune response may be an effective strategy for treating COVID-19. Mesenchymal stem cells (MSCs) and their derived exosomes (MSCs-Exo) have potent homing abilities, immunomodulatory functions, regenerative repair, and antifibrotic effects, promising an effective tool in treating COVID-19. In this paper, we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19. We also summarize relevant recent clinical trials, including the source of cells, the dosage and the efficacy, and the clinical value and problems in this field, providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.

The Antimicrobial Peptide Tilapia Piscidin 4 Induced the Apoptosis of Bladder Cancer Through ERK/SIRT1/PGC-1α Signaling Pathway.

Marine antimicrobial peptides have been demonstrated in numerous studies to possess anti-cancer properties. This research investigation aimed to explore the fundamental molecular mechanisms underlying the antitumor activity of Tilapia piscidin 4 (TP4), an antimicrobial peptide, in human bladder cancer. TP4 exhibited a remarkable inhibitory effect on the proliferation of bladder cancer cells through cell cycle arrest at the G2/M phase. Additionally, TP4 upregulated the expression of cleaved caspase-3, caspase-9, and PARP, leading to the activation of apoptotic pathways in bladder cancer cells. TP4 exhibit a marked rise in mitochondria reactive oxygen species, leading to the subsequent loss of potential for the mitochondrial membrane. Furthermore, the inhibition of mitochondrial oxidative phosphorylation resulted in a decrease in downstream ATP production. Meanwhile, TP4-treated bladder cancer cells showed an increase in Bax and ERK but a decrease in SIRT1, PGC-1α, and Bcl2. ERK activation, SIRT1/PGC-1α-axis, and TP4-induced apoptosis were all significantly reversed by the ERK inhibitor SCH772984. Finally, the inhibitory effect of TP4 on tumor growth has been confirmed in a zebrafish bladder cancer xenotransplantation model. These findings suggest that TP4 may be a potential agents for human bladder cancer through apoptosis induction, ERK activation, and the promotion of SIRT1-mediated signaling pathways.

Exaggerated sensitivity to threat and reduced medial prefrontal engagement during threat generalization in reactive aggressive adolescents.

Aggressive adolescents tend to exhibit abnormal fear acquisition and extinction, and reactive aggressive adolescents are often more anxious. However, the relationship between fear generalization and reactive aggression (RA) remains unknown. According to Reactive-Proactive Aggression Questionnaire (RPQ) scores, 61 adolescents were divided into two groups, namely, a high RA group (N = 30) and a low aggression (LA) group (N = 31). All participants underwent three consecutive phases of the Pavlovian conditioning paradigm (i.e., habituation, acquisition, and generalization), and neural activation of the medial prefrontal cortex (mPFC) was assessed by functional near-infrared spectroscopy (fNIRS). The stimuli were ten circles with varying sizes, including two conditioned stimuli (CSs) and eight generalization stimuli (GSs). A scream at 85 dB served as the auditory unconditioned stimulus (US). The US expectancy ratings of both CSs and GSs were higher in the RA group than in the LA group. The fNIRS results showed that CSs and GSs evoked lower mPFC activation in the RA group compared to the LA group during fear generalization. These findings suggest that abnormalities in fear acquisition and generalization are prototypical dysregulations in adolescents with RA. They provide neurocognitive evidence for dysregulated fear learning in the mechanisms underlying adolescents with RA, highlighting the need to develop emotional regulation interventions for these individuals.

Structural investigations on the mitochondrial uncouplers niclosamide and FCCP.

There has been renewed interest in using mitochondrial uncoupler compounds such as niclosamide and carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) for the treatment of obesity, hepatosteatosis and diseases where oxidative stress plays a role. However, both FCCP and niclosamide have undesirable effects that are not due to mitochondrial uncoupling, such as inhibition of mitochondrial oxygen consumption by FCCP and induction of DNA damage by niclosamide. Through structure-activity analysis, we identified FCCP analogues that do not inhibit mitochondrial oxygen consumption but still provided good, although less potent, uncoupling activity. We also characterized the functional role of the niclosamide 4'-nitro group, the phenolic hydroxy group and the anilide amino group in mediating uncoupling activity. Our structural investigations provide important information that will aid further drug development.

The global pattern of epiphytic liverwort disparity: insights from Frullania.

The geographical and ecological patterns of morphological disparity are crucial to understand how species are assembled within communities in the context of the evolutionary history, morphological evolution and ecological interactions. However, with limited exceptions, rather few studies have been conducted on the global pattern of disparity, particularly in early land plants. Here we explored the spatial accumulation of disparity in a morphologically variable and species rich liverwort genus Frullania in order to test the hypothesis of latitude disparity gradient. We compiled a morphological data set consisting of eight continuous traits for 244 currently accepted species, and scored the species distribution into 19 floristic regions worldwide. By reconstructing the morphospace of all defined regions and comparisons, we identified a general Gondwana-Laurasia pattern of disparity in Frullania. This likely results from an increase of ecological opportunities and / or relaxed constraints towards low latitudes. The lowest disparity occurred in arid tropical regions, largely due to a high extinction rate as a consequence of paleoaridification. There was weak correlation between species diversity and disparity at different spatial scales. Furthermore, long-distance dispersal may have partially shaped the present-day distribution of Frullania disparity, given its frequency and the great contribution of widely distributed species to local morphospace. This study not only highlighted the crucial roles of paleoenvironmental changes, ecological opportunities, and efficient dispersal on the global pattern of plant disparity, but also implied its dependence on the ecological and physiological function of traits.

Epigenetic silencing schlafen-11 sensitizes esophageal cancer to ATM inhibitor.

BACKGROUND: Targeting DNA damage response (DDR) pathway is a cutting-edge strategy. It has been reported that Schlafen-11 (SLFN11) contributes to increase chemosensitivity by participating in DDR. However, the detailed mechanism is unclear. AIM: To investigate the role of SLFN11 in DDR and the application of synthetic lethal in esophageal cancer with SLFN11 defects. METHODS: To reach the purpose, eight esophageal squamous carcinoma cell lines, 142 esophageal dysplasia (ED) and 1007 primary esophageal squamous cell carcinoma (ESCC) samples and various techniques were utilized, including methylation-specific polymerase chain reaction, CRISPR/Cas9 technique, Western blot, colony formation assay, and xenograft mouse model. RESULTS: Methylation of SLFN11 was exhibited in 9.15% of (13/142) ED and 25.62% of primary (258/1007) ESCC cases, and its expression was regulated by promoter region methylation. SLFN11 methylation was significantly associated with tumor differentiation and tumor size (both P < 0.05). However, no significant associations were observed between promoter region methylation and age, gender, smoking, alcohol consumption, TNM stage, or lymph node metastasis. Utilizing DNA damaged model induced by low dose cisplatin, SLFN11 was found to activate non-homologous end-joining and ATR/CHK1 signaling pathways, while inhibiting the ATM/CHK2 signaling pathway. Epigenetic silencing of SLFN11 was found to sensitize the ESCC cells to ATM inhibitor (AZD0156), both in vitro and in vivo. CONCLUSION: SLFN11 is frequently methylated in human ESCC. Methylation of SLFN11 is sensitive marker of ATM inhibitor in ESCC.

[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Exploring the 'black box' of anxiety: An ERP study of non-consciously triggered fear generalization.

Individuals with anxiety disorders frequently display heightened fear responses, even in situations where there is no imminent danger. We hypothesize that these irrational fear responses are related to automatic processing of fear generalization. The initial automatic detection of stimuli often operates at a non-conscious level. However, whether fear generalization can occur when the cues are not perceived consciously remains unclear. The current study investigated the neurocognitive mechanisms underlying fear conditioning and its non-conscious and conscious generalization using a backward masking paradigm, combined with analysis of event-related potentials from electroencephalographic recordings. Behaviorally, participants showed heightened shock expectancy in response to non-conscious perceived generalization stimuli compared to those perceived consciously. Nonetheless, participants could not consciously distinguish between danger and safe cues in non-conscious trials. Physiologically, danger cues evoked larger frontal N1 amplitudes than safety cues in non-conscious trials, suggesting enhanced attention vigilance towards danger cues in the early sensory processing stage. Meanwhile, when fear generalization was conscious, it was accompanied by a larger P2 amplitude, indicating attention orientation or stimulus evaluation. In addition, fear conditioning was associated with sustained discrimination on P2, P3, and LPP. These findings collectively suggest that non-conscious fear generalization occurs at the neural level, yet additional control conditions are required to confirm this phenomenon on the US expectancy. Thus, non-consciously fear generalization may represent a mechanism that could trigger automatic irrational fear, highlighting the need for further research to explore therapeutic targets in anxiety disorders.

A negative feedback loop between TET2 and leptin in adipocyte regulates body weight.

Ten-eleven translocation (TET) 2 is an enzyme that catalyzes DNA demethylation to regulate gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, functioning as an essential epigenetic regulator in various biological processes. However, the regulation and function of TET2 in adipocytes during obesity are poorly understood. In this study, we demonstrate that leptin, a key adipokine in mammalian energy homeostasis regulation, suppresses adipocyte TET2 levels via JAK2-STAT3 signaling. Adipocyte Tet2 deficiency protects against high-fat diet-induced weight gain by reducing leptin levels and further improving leptin sensitivity in obese male mice. By interacting with C/EBPα, adipocyte TET2 increases the hydroxymethylcytosine levels of the leptin gene promoter, thereby promoting leptin gene expression. A decrease in adipose TET2 is associated with obesity-related hyperleptinemia in humans. Inhibition of TET2 suppresses the production of leptin in mature human adipocytes. Our findings support the existence of a negative feedback loop between TET2 and leptin in adipocytes and reveal a compensatory mechanism for the body to counteract the metabolic dysfunction caused by obesity.

Energy harvesting from acid mine drainage using a highly proton/ion-selective thin polyamide film.

A huge chemical potential difference exists between the acid mine drainage (AMD) and the alkaline neutralization solution, which is wasted in the traditional AMD neutralization process. This study reports, for the first time, the harvest of this chemical potential energy through a controlled neutralization of AMD using H+-conductive films. Polyamide films with controllable thickness achieved much higher H+ conductance than a commercially available cation exchange membrane (CEM). Meanwhile, the optimal polyamide film had an excellent H+/Ca2+ selectivity of 63.7, over two orders of magnitude higher than that of the CEM (0.3). The combined advantages of fast proton transport and high proton/ion selectivity greatly enhanced the power generation of the AMD battery. The power density was 3.1 W m-2, which is over one order of magnitude higher than that of the commercial CEM (0.2 W m-2). Our study provides a new sustainable solution to address the environmental issues of AMD while simultaneously enabling clean energy production.

Optimizing analytical precision in the identification of synthetic cathinones and isomers: a comparative assessment of diverse GC-MS operating parameters.

Analyzing new psychoactive substances (NPSs) in forensic laboratories present a formidable challenge globally. Within illicit drug analysis, gas chromatography-mass spectrometry (GC-MS) emerges as a robust analytical tool. This study endeavors to assess and compare peak resolution in the analysis of illicit drugs, specifically focusing on 21 synthetic cathinones, encompassing 9 cathinone isomers. Varied GC-MS operating conditions, including distinct GC-MS columns and thermal gradients, were systematically employed for the simultaneous analysis of these synthetic cathinones. The study utilized HP-1 nonpolar and HP-5MS low-bleed columns to achieve optimal analyte resolution through modulation of GC-MS oven conditions. Mass spectra were meticulously recorded within a mass-to-charge (m/z) range spanning from 40 to 500 in full scan mode. The data showed that the cathinone isomers slightly differed in retention times and mass spectra. The GC oven conditions affected the peak resolution for chromatographic separation even with the same column. The peak resolution improved using a slower thermal gradient heat speed with a prolonged analysis time. Conclusively, the interplay of GC columns and thermal gradients emerged as pivotal factors impacting peak resolution in the analysis of illicit drugs. These empirical insights contribute to a nuanced understanding of peak resolution dynamics and facilitate the identification of synthetic cathinones, including their isomers, in seized materials through the judicious application of GC-MS methodologies.

Association between Marital Status and Cognitive Impairment in a Multi-Ethnic Asian Population.

OBJECTIVE: This study aims to examine the potential factors associated with marital status and determine the association between marital status and cognitive impairment in a multi-ethnic Asian population. METHOD: This study included 2321 participants from Singapore Multi-Ethnic Cohort revisit study (aged 40-89). Participants were classified into married and unmarried group at baseline and follow-up according to self-reported marital status. Mini-Mental Status Examination (MMSE) was administered, and cognitive impairment was defined as a MMSE <26. We conducted both cross-sectional and longitudinal analyses to examine the association of marital status at one time point as well as marital transition with cognitive impairment. RESULTS: Of the 2321 participants, a total of 1914 (82.5%) were married. The factors associated with marital status included younger age, male sex, higher household income, higher education, and higher physical activity levels. Additionally, married participants also had higher alternative healthy eating index (AHEI-2010) scores, and a lower burden of hypertension and diabetes. Among those who were married, the median (Q1, Q3) MMSE score was 29 (28,30) while those who were unmarried was 29 (27, 30) (p <0.01). Participants who had never been married had the highest odds of cognitive impairment compared to their married counterparts (Model III: OR=1.48, 95% CI: 1.03, 2.14). Older age (p-interaction value=0.003) and Indian ethnicity (p-interaction value=0.028) further strengthened these associations. CONCLUSION: Marriage was associated with lower odds of cognitive impairment. Marriage provides social support, companionship, and engagement in mentally stimulating activities contributing to better cognitive health. By identifying risk factors such as marital status, interventions and support systems can be developed to promote healthy cognitive aging.

Synergistic effects of combined probiotics Bacillus pumilis D5 and Leuconostoc mesenteroide B4 on immune enhancement and disease resistance in Litopenaeus vannamei.

This study investigated the effects of two distinct probiotics, Leuconostoc mesenteroides B4 (B4) and Bacillus pumilus D5 (D5), along with their combination, on the diet of white shrimp (Litopenaeus vannamei) during an eight-week feeding trial. The diets tested included B4 + dextran at 107 CFU/g feed (the B4 group), D5 alone at 107 CFU/g feed (the D5 group), and a combination of B4 + dextran and D5 at 5 × 106 CFU/g feed each (the B4+dextran + D5 group). Relative to the control group, those administered probiotics exhibited moderate enhancements in growth. By the eighth week, the weight gain for the B4, D5, and B4+D5 groups was 696.50 ± 78.15%, 718.53 ± 130.73%, and 693.05 ± 93.79%, respectively, outperforming the control group's 691.66 ± 31.10% gain. The feed conversion ratio was most efficient in the B4 group (2.16 ± 0.06), closely followed by B4+D5 (2.21 ± 0.03) and D5 (2.22 ± 0.06), with the control group having the highest ratio (2.27 ± 0.03). While phenoloxidase activity was somewhat elevated in the B4 and D5 groups, no significant differences were noted in respiratory burst activity or total hemocyte count across all groups. Challenge tests at weeks 4 and 8 showed that the B4 + D5 combination offered superior protection against AHPND-causing Vibrio parahaemolyticus. The 4-week cumulative survival rate was highest in shrimp treated with B4 + dextran + D5 (56.25%), followed by B4 + dextran (31.25%), control (18.75%), and lowest in D5 (12.5%). By week 8, the B4 + dextran + D5 (43.75%) and B4 + dextran (37.5%) groups significantly outperformed the control group (6.25%, p < 0.05), with no significant difference observed between the D5 group (37.5%) and the control group at day 56. Analysis of the shrimp's foregut microbiota revealed an increase in unique OTUs in the B4 and B4 + D5 groups. Compared to the control, Proteobacteria abundance was reduced in all probiotic groups. Potential pathogens like Vibrio, Bacteroides, Neisseria, Botrytis, Clostridioides, and Deltaentomopoxvirus were detected in the control but were reduced or absent in probiotic groups. Beneficial microbes such as Methanobrevibacter and Dictyostelium in the B4+D5 group, and Sugiyamaella in the B4 group, showed significant increases. Probiotics also led to higher transcript levels of nitric oxide synthase in the hemocytes, and lysozyme and transglutaminase in the midgut, along with lysozyme and α2-macroglobulin in the foregut. Notably, the combined B4 + D5 probiotics synergistically enhanced the expression of superoxide dismutase and prophenoloxidase in the foregut, indicating an improved immune response. In summary, this study demonstrates that the probiotics evaluated, especially when used in combination, significantly boost the expression of specific immune-related genes, enhance the bacterial diversity and richness of the intestine, and thus prevent the colonization and proliferation of Vibrio spp. in L. vannamei.

Exploring the relationship between digital transformation and green innovation: The mediating role of financing modes.

Green innovation is important and beneficial for the green development of enterprises. The development of digital technology could improve the asymmetry of information and affect the enterprise's financing modes. Currently, a definitive conclusion about the relationship between the digital transformation and green technology innovation has not reached. Additionally, studies have not yet fully explored the impact pathways of corporate digital transformation on green innovation through corporate financing modes. To fill this void, this study collected data of Chinese A-share listed companies from 2010 to 2020. The empirical analysis results showed that digital transformation significantly enhanced enterprises' green innovation abilities. Furthermore, mediating models were utilized to explore how enterprise financing modes mediate the impact of digital transformation on the enterprise green innovation. Results indicated that through internal financing and bank loans as "bridges", digital transformation promoted enterprise green innovation. However, digital transformation did not have a significant impact on enterprise green innovation through venture capital. Moreover, heterogeneity analyses revealed significant differences among different groups of enterprises. This study expands the research field related to digital transformation and enterprise green innovation by providing empirical evidence to uncover the impact of digital transformation on enterprise green innovation. Findings of this study contribute not only to enterprise managerial decision-makers to better leverage digital transformation through corporate financing to accelerate green innovation, but also to government policymakers to design policies to stimulate enterprise green innovation.

A zincophilic separator with directional alignment and pore hydrophilicity towards stable aqueous zinc metal batteries.

A zincophilic PAN@Zn(OTF)2 (PZO) separator with an extremely thin thickness of 65.6 µm is introduced. This separator with a low cost of 6.1 $ m-2, exhibiting excellent mechanical and wettability properties. The cell with the PZO separator exhibits impressive electrochemical performances both in symmetrical Zn||Zn cell and Zn||NVO full cell.

Correction: Development of a Humanized Antibody with High Therapeutic Potential against Dengue Virus Type 2.

[This corrects the article DOI: 10.1371/journal.pntd.0001636.].

Sigmoidal relationship between liver fat content and nonalcoholic fatty liver disease in Chinese adults.

PURPOSE: To explore the relationship between liver fat content (LFC) and nonalcoholic fatty liver disease (NAFLD) and determine the new threshold of LFC to diagnose NAFLD. METHODS: The data from questionnaire survey, general physical examination, laboratory examination, and image examination were collected. Multivariate regression analysis, receiver operating characteristic curve analysis, smooth curve fitting, and threshold effect analysis were performed using the R software to investigate the relationship between LFC and NAFLD and to identify the new threshold of LFC to diagnose NAFLD. RESULTS: The prevalence of NAFLD was 30.42%, with a significantly higher prevalence in men than in women. Regression analyses demonstrated that LFC odds ratio [95% confidence interval (CI)] was 1.28 (95% CI: 1.24-1.31) in fully-adjust model. Analysis of the LFC quartile, with Q1 as a reference, revealed that the odds ratios of NAFLD were 1.47 (95% CI: 1.08-1.99), 2.29 (95% CI: 1.72-3.06), and 10.02 (95% CI: 7.45-13.47) for Q2, Q3, and Q4 groups, respectively. Smooth curve fitting and threshold effect analysis displayed a nonlinear relationship between LFC and NAFLD, and the threshold was 4.5%. The receiver operating characteristic curve indicated that when LFC was 4.5%, the area under curve (95% CI) was 0.80 (0.79-0.82), and the sensitivity and specificity of LFC in diagnosing NAFLD were 0.64% and 0.82%, respectively. CONCLUSION: The relationship between LFC and NAFLD was sigmoidal, with an inflection point of 4.5%.

Synergistic acceleration of machine learning and molecular docking for prostate-specific antigen ligand design.

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.

The effect of omentoplasty in various surgical operations: Systematic review and meta-analysis.

BACKGROUND: Omentoplasty is commonly used in various surgeries. However, its effectiveness is unsure due to lack of convincing data and research. To clarify the impact of omentoplasty on postoperative complications of various procedures, this systematic review and meta-analysis was performed. METHODS: A systematic review of published literatures from four databases: PubMed, Web of Science, Cochrane Library, and Embase before July 14, 2022. We primarily included publications on five major surgical operations performed in conjunction with omentoplasty: thoracic surgery, esophageal surgery, gastrointestinal surgery, pelvi-perineal surgery, and liver surgery. The protocol was registered in PROSPERO. RESULTS: This review included 25 273 patients from 91 studies (n=9 670 underwent omentoplasty). Omentoplasty was associated with a lower risk of overall complications particularly in gastrointestinal (RR 0.53; 95%CI 0.39-0.72) and liver surgery (RR 0.54; 95%CI 0.39-0.74). Omentoplasty reduced the risk of postoperative infection in thoracic (RR 0.38; 95%CI 0.18-0.78) and liver surgery (RR 0.39; 95%CI 0.29-0.52). In patients undergoing esophageal (RR 0.89; 95%CI 0.80-0.99) and gastrointestinal (RR 0.28; 95%CI 0.23-0.34) surgery with a BMI greater than 25, omentoplasty is significantly associated with a reduced risk of overall complications compared to patients with normal BMI. No significant differences were found in pelvi-perineal surgery, except infection in patients whose BMI ranged from 25 kg/m2 to 29.9 kg/m2 (RR 1.25; 95%CI 1.04-1.50) and anastomotic leakage in patients aged over 60 (RR 0.59; 95%CI-0.39-0.91). CONCLUSION: Omentoplasty can effectively prevent postoperative infection. It is associated with a lower incidence of multiple postoperative complications in gastrointestinal and liver surgery.