Chiroptical Activity Amplification of Chiral Metal Nanoclusters via Surface/Interface Solidification.

It remains a grand challenge to amplify the chiroptical activity of chiral metal nanoclusters (NCs) although it is desirable for fundamental research and practical application. Herein, we report a strategy of surface/interface solidification (SIS) for enhancing the chiroptical activity of gold NCs. Structural analysis of [Au19(2R,4R/2S,4S-BDPP)6Cl2]3+ (BDPP is 2,4-bis(diphenylphosphino)pentane) clusters reveals that one of the interfacial gold atoms is flexible between two sites and large space is present on the surface, thus hampering chirality transfer from surface chiral ligands to metal core and leading to low chiroptical activity. Following SIS by filling the flexible sites and replacing chlorides with thiolate ligands affords another pair of [Au20(2R,4R/2S,4S-BDPP)6(4-F-C6H4S)2]4+, which shows a more compact and organized structure and thus an almost 40-fold enhancement of chiroptical activity. This work not only provides an efficient approach for amplifying the chiroptical activity of metal nanoclusters but also highlights the significance of achiral components in shaping chiral nanostructures.

Prognostic value of aspartate aminotransferase/alanine aminotransferase ratio in hepatocellular carcinoma after hepatectomy.

BACKGROUND: The prognostic significance of the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio in hepatocellular carcinoma remains uncertain. The aim of the current study was to evaluate the association between the AST/ALT ratio and prognosis in patients with hepatocellular carcinoma after hepatectomy, and to explore the role of underlying liver diseases as mediators. METHODS: This retrospective study included patients with hepatocellular carcinoma who underwent hepatectomy between January 2014 and January 2018 at two Chinese hospitals. The maximally selected rank statistic and g-computation approach were used to quantify and visualize the association between the AST/ALT ratio and overall survival or recurrence-free survival. The role of mediators (chronic hepatitis B, hepatic steatosis and liver cirrhosis) was analysed. RESULTS: Among the 1519 patients (mean(s.d.) age at baseline, 50.5(11.3) years), 1309 (86.2%) were male. During a median follow-up of 46.0 months, 514 (33.8%) patients died and 358 (23.6%) patients experienced recurrence. The optimal cut-off value for the AST/ALT ratio was 1.4, and the AST/ALT ratio greater than or equal to 1.4 was independently associated with a 39.0% increased risk of death and a 30.0% increased risk of recurrence (overall survival: hazard ratio (HR), 1.39; 95% c.i. 1.15 to 1.68; recurrence-free survival: HR, 1.30; 95% c.i. 1.12 to 1.52) after adjusting for confounders. Chronic hepatitis B significantly mediated the association of the ratio of AST/ALT with both overall survival and recurrence-free survival (20.3% for overall survival; 20.1% for recurrence-free survival). CONCLUSION: The AST/ALT ratio greater than or equal to 1.4 was associated with shorter overall survival and recurrence-free survival in patients with hepatocellular carcinoma after hepatectomy, and chronic hepatitis B may play a role in their association.

Interacting and joint effects of triglyceride-glucose index (TyG) and body mass index on stroke risk and the mediating role of TyG in middle-aged and older Chinese adults: a nationwide prospective cohort study.

BACKGROUND: Individuals who are overweight or obese often develop insulin resistance, mediation of the association between body mass index (BMI) and stroke risk through the triglyceride-glucose index (TyG) seems plausible but has not been investigated. This study aims to examine whether TyG mediates associations of BMI with stroke risk and the extent of interaction or joint relations of TyG and BMI with stroke outcome. METHODS: The China Health and Retirement Longitudinal Study, initiated in 2011, is a nationally representative, ongoing prospective cohort study involving 8 231 middle-aged and older Chinese adults without a stroke history at baseline. Exposures examined include BMI and the TyG, the latter being the logarithmized product of fasting triglyceride and glucose concentrations. The primary study outcome is stroke incidence, as determined through self-reports, with a follow-up period extending from June 1, 2011, to June 30, 2018. RESULTS: Of the 8 231 participants, 3 815 (46.3%) were men; mean (SD) age was 59.23 (9.32) years. During a median follow-up of 7.1 years, 585 (7.1%) participants developed stroke. The TyG was found to mediate the association between BMI and incident stroke, proportions mediated were 16.3% for BMI in the 24.0-27.9 kg/m2 group and 53.8% for BMI ≥ 28.0 kg/m2 group. No significant multiplicative and additive interactions were found between BMI and TyG on incident stroke (Additive: RERI = 1.78, 95% CI - 1.29-4.86; Multiplicative, HR = 1.40, 95% CI 0.86-2.27). HRs for individuals with BMI ≥ 28.0 kg/m2 and quartile 4 of TyG compared with those with BMI < 24.0 kg/m2 and quartile 1 of TyG were 2.05 (95% CI 1.37-3.06) for incident stroke. Combining BMI and TyG enhanced predictive performance for stroke when compared to their individual (AUCBMI+TyG vs AUCBMI vs AUCTyG, 0.602 vs 0.581 vs 0.583). CONCLUSIONS: TyG appeared to be associated with stroke risk and mediates more than 50% of the total association between BMI and stroke in middle-aged and older Chinese adults. Public health efforts aiming at the reduction of body weight might decrease the stroke risk due to insulin resistance and the burden of stroke.

Cardiac-specific deletion of BRG1 ameliorates ventricular arrhythmia in mice with myocardial infarction.

Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na+ current (INa) and transient outward potassium current (Ito), as well as the expression of Nav1.5 and Kv4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and ß-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5A and KCND3, thereby influencing the incidence of VA post-MI.

Impact of Sjögren's syndrome on maternal and fetal outcomes following pregnancy: a systematic review and meta-analysis of studies published between years 2007-2022.

OBJECTIVE: To show the impact of Sjögren's syndrome (SS) on maternal and fetal outcomes following pregnancy. METHODS: We performed a literature search based on PubMed, Web of science, Wan fang, China National Knowledge Infrastructure and ProQuest databases from 1 January 2007 to 6 November 2022. Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the certainty of the evidence. Systematic reviews and meta-analyses were performed using RevMan 5.3 software. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Trial sequential analyses were performed by TSA 0.9. RESULTS: Nine studies with 2341 patients and 2472 pregnancies with SS were included in our analysis. This current analysis showed pregnancy hypertension and preeclampsia/eclampsia to be significantly higher in pregnant women with SS compared to pregnant women without SS (OR: 1.65, 95% CI: 1.04-2.63; P = 0.03), (OR: 2.06, 95% CI: 1.16-3.65; P = 0.01) respectively. Cesarean section, thromboembolic disease, premature rupture of membranes, and spontaneous abortion were also significantly higher in the SS women with OR: 2.07, 95% CI: 1.48-2.88; P < 0.0001, OR: 9.45, 95% CI: 1.99-44.87; P = 0.005, OR: 1.36, 95% CI: 1.13-1.64; P = 0.001, OR: 9.30, 95% CI: 4.13-20.93; P < 0.00001, respectively. Significantly higher premature births were observed with infants who were born from SS mothers (OR: 2.19, 95% CI: 1.54-3.12; P < 0.0001). Infants defined as 'small for gestational age/intrauterine growth restriction' and 'weighing < 2500 g' were also significantly higher in patients suffering from SS (OR: 2.26, 95% CI: 1.38-3.70; P = 0.001), (OR: 3.84, 95% CI: 1.39-10.61; P = 0.009) respectively. In addition, live birth significantly favored infants who were born from mothers without SS (OR: 21.53, 95% CI: 8.36-55.44; P < 0.00001). Subgroup analysis by sample size revealed that pregnancy hypertension risk has significantly increased in small cohort (OR: 2.74, 95%CI: 1.45-5.18), and a slight increase was found in population-based studies (OR: 1.14, 95%CI: 0.91-1.43). In both small cohorts and population-based researches, cesarean section was significantly higher in SS (OR: 2.13, 95% CI: 1.29, 3.52; OR: 1.85, 95% CI: 1.29-2.64, respectively). The number of infants with intrauterine growth restriction did not grow in the population-based researches (OR: 2.07, 95%CI: 0.92-4.66) although there has been an increase in small reports (OR: 2.53, 95%CI: 1.16-5.51). Subgroup analysis was conducted on the basis of study location (not Asian vs. Asian countries) indicated that cesarean section was significantly higher in SS in both countries (OR: 1.69, 95% CI: 1.31-2.18; OR: 3.37, 95% CI: 2.39-4.77, respectively). CONCLUSION: This meta-analysis has shown SS to have a high impact on maternal and fetal outcomes following pregnancy.

Smart Stimulation Response of a Pyrene-Based Lanthanide(III) MOF: Fluorescence Enhancement to HX (F and Cl) or R-COOH and Artificial Applicable Film on HCl Vapor Sensing.

Toxic acids produced by industries are major hazards to the environment and human health, and luminescent pyrene-based crystalline metal-organic frameworks (MOFs) demonstrate promising performance in the detection of toxic acids. Herein, two novel isostructural 3D porous lanthanide MOFs, H3O·[Ln3(TBAPy)2(µ2-H2O)2(OH)2]·2DMA·2Diox·6.5H2O (Ln = Pr (1) and Ce (2); H4TBAPy (1,3,6,8-tetrakis(p-benzoic acid)pyrene); and DMA: N,N-dimethylacetamide) were synthesized, which showed alb topology. Based on the protonation and hydrogen bond mechanism, complex 1 could be used as a fluorescence recognition sensor for HX (X = F, Cl, Br, and I) acid solutions with different luminescence behaviors. It is worth noting that complex 1 exhibited high sensitivity in the fluorescence enhancement sensing of hydrofluoric acid, oxalic acid, and trichloroacetic acid. In particular, complex 1 had a low limit of detection (LOD) for OA (0.1 µM) and was applied to real monitoring of orange fruit samples. In addition, the PVA@1 film could selectively, sensitively, and quantitatively respond to hydrochloric acid (HCl) vapor through fluorescent quenching; due to its protonation and adsorption capacity, the LOD was 0.18 ppm. Therefore, the portable optical device, the PVA@1 film, can detect HCl gas in trace amounts, achieving the ultimate goal of real-time and rapid detection, which has potential application value for industrial production safety.

Sexual health in women with Sjogren's syndrome: A review.

BACKGROUND: Rheumatic diseases, mainly affecting women, including rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, etc., are chronic, inflammatory, autoimmune disorders that may involve multiple organs or systems and are closely related to sexual health, which is an important aspect of human physical and mental health. Sjogren's syndrome (SS) is the second most common rheumatic illnesses after rheumatoid arthritis with a female predominance. At present, the research on sexual health of female SS patients is still scarce and difficult to summarize. OBJECTIVES: The objective of our study was to systematically review the literature for the influence of maternal SS on sexual health, such as sexual function, sex hormones, fertility, and pregnancy outcomes. METHODS: We performed a comprehensive literature search based on PubMed and Web of science databases from inception to 1 November 2022. Outcomes were divided into 4 categories: sex hormones, sexual function, fertility, and pregnancy and offspring outcomes. RESULTS: A total of 756 potentially eligible papers were retrieved. After eliminating duplicate articles and reviewing the titles and abstracts to exclude records, we read the remaining 92 articles in full for further evaluation, and selected 42 studies. Results on sex hormones, sexual function, fertility and pregnancy and offspring outcomes were reported in 13, 12, 3 and 14 SS-related articles, respectively. The levels of some sex hormones in SS patients may have undergone changes. Female patients with SS have a high prevalence of sexual dysfunction compared with controls. Most studies suggested SS had an adverse impact on maternal and fetal outcomes following pregnancy. However, there is insufficient evidence that directly indicating the fertility of SS women is diminished. CONCLUSIONS: In summary, certain aspects of sexual health (sexual function, sex hormones and pregnancy outcomes) are impaired in SS women. Screening for sexual health problems in SS female should become an integral part of medical clinical practice. Rheumatologists should be aware of this association and collaborate with gynecologists, obstetricians, psychologists, and other experts on this issue to determine appropriate therapeutic approaches.

The role of BRG1 in epigenetic regulation of cardiovascular diseases.

Cardiovascular diseases have been closely linked to abnormal epigenetic regulation. In the context of epigenetic regulation, BRG1, a pivotal SWI/SNF chromatin remodeling enzyme, emerges as a key epigenetic regulator with significant impact on the development and progression of cardiovascular disorders. From the perspective of epigenetic regulation of cardiovascular diseases, BRG1 emerges as a pivotal SWI/SNF chromatin remodeling enzyme, functioning as a key epigenetic regulator. It exerts substantial influence on the development and progression of cardiovascular disorders by exerting precise control over gene expression and protein levels. Therefore, a comprehensive understanding of BRG1's epigenetic regulatory role in cardiovascular disease is essential for unraveling its underlying pathophysiological mechanisms. This paper summarizes and discusses the function of BRG1 in the epigenetic regulation of cardiovascular diseases.

Changes in the triglyceride glucose-body mass index estimate the risk of stroke in middle-aged and older Chinese adults: a nationwide prospective cohort study.

BACKGROUND: Stroke was reported to be highly correlated with the triglyceride glucose-body mass index (TyG-BMI). Nevertheless, literature exploring the association between changes in the TyG-BMI and stroke incidence is scant, with most studies focusing on individual values of the TyG-BMI. We aimed to investigate whether changes in the TyG-BMI were associated with stroke incidence. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which is an ongoing nationally representative prospective cohort study. The exposures were changes in the TyG-BMI and cumulative TyG-BMI from 2012 to 2015. Changes in the TyG-BMI were classified using K-means clustering analysis, and the cumulative TyG-BMI was calculated as follows: (TyG-BMI2012 + TyG-BMI2015)/2 × time (2015-2012). Logistic regressions were used to determine the association between different TyG-BMI change classes and stroke incidence. Meanwhile, restricted cubic spline regression was applied to examine the potential nonlinear association of the cumulative TyG-BMI and stroke incidence. Weighted quantile sum regression was used to provide a comprehensive explanation of the TyG-BMI by calculating the weights of FBG, triglyceride-glucose (TG), and BMI. RESULTS: Of the 4583 participants (mean [SD] age at baseline, 58.68 [9.51] years), 2026 (44.9%) were men. During the 3 years of follow-up, 277 (6.0%) incident stroke cases were identified. After adjusting for potential confounders, compared to the participants with a consistently low TyG-BMI, the OR for a moderate TyG-BMI with a slow rising trend was 1.01 (95% CI 0.65-1.57), the OR for a high TyG-BMI with a slow rising trend was 1.62 (95% CI 1.11-2.32), and the OR for the highest TyG-BMI with a slow declining trend was 1.71 (95% CI 1.01-2.89). The association between the cumulative TyG-BMI and stroke risk was nonlinear (Passociation = 0.017; Pnonlinearity = 0.012). TG emerged as the primary contributor when the weights were assigned to the constituent elements of the TyG-BMI (weight2012 = 0.466; weight2015 = 0.530). CONCLUSIONS: Substantial changes in the TyG-BMI are independently associated with the risk of stroke in middle-aged and older adults. Monitoring long-term changes in the TyG-BMI may assist with the early identification of individuals at high risk of stroke.

Adjuvant immune checkpoint inhibitors associated with higher recurrence-free survival in postoperative hepatocellular carcinoma (PREVENT): a prospective, multicentric cohort study.

BACKGROUND: Adjuvant therapy may improve survival of patients with hepatocellular carcinoma (HCC) after curative resection. This study compared safety and efficacy outcomes between patients at high risk of recurrence who received different types of adjuvant therapy or no such therapy after hepatic resection for HCC. METHODS: Recurrence-free survival (RFS), overall survival, and adverse events were compared among patients who received adjuvant immune checkpoint inhibitors (ICIs) alone, ICIs with tyrosine kinase inhibitors (TKIs), or no adjuvant therapy between 13 March 2019 and 19 March 2022. This study was registered on ClinicalTrials.gov (NCT05221398). RESULTS: Of the 517 patients in final analysis, 432 (83.6%) received no adjuvant therapy, 53 (10.2%) received ICIs alone, and 32 (6.2%) received adjuvant ICIs and TKIs. During median follow-up of 34.0 months (IQR 27.8 to 41.6 months), RFS was significantly longer among patients who received either type of adjuvant therapy (25.2 months, 95%CI 16.4-34.0) than among those who received none (16.1 months, 95%CI 12.9-19.4), and this difference remained significant after propensity score matching (HR 0.52, 95%CI 0.35-0.76, P = 0.004). Overall survival was unaffected by either type of adjuvant therapy, while significant difference was observed between patients who received adjuvant therapy or not after propensity score matching (HR 0.31, 95%CI 0.17-0.59, P = 0.005). The rate of grade 3 or 4 adverse events was similar between the two types of adjuvant therapy. CONCLUSIONS: ICIs alone or with TKIs may improve RFS of patients at high risk of HCC recurrence after curative resection.

PFI-3 induces vasorelaxation with potency to reduce extracellular calcium influx in rat mesenteric artery.

Background: PFI-3 is a small-molecule inhibitor that targets the bromodomains (BRDs) of Brahma-related gene 1 (BRG1). This monomeric compound, which has high selectivity and potent cellular effects, has recently been developed. Although PFI-3 has been reported as a potential therapeutic agent targeting thrombomodulin, its role in the regulation of vascular function remains unknown. Therefore, we aimed to investigate the impact of PFI-3 on arterial vessel tone. Methods: A microvascular tension measurement device (DMT) was utilized to identify alterations in vascular tension within the mesenteric artery. To detect variations in cytosolic [Ca2+]i, a Fluo-3/AM fluorescent probe and fluorescence microscope were employed. Additionally, whole-cell patch clamp techniques were utilized to evaluate the activity of L-type voltage-dependent calcium channels (VDCCs) in cultured arterial smooth muscle cells (A10 cells). Results: PFI-3 exerted a dose-dependent relaxation effect on rat mesenteric arteries with both intact and denuded endothelium after phenylephrine (PE)- and high-K+-induced constriction. PFI-3-induced vasorelaxation was not affected by the presence of L-NAME/ODQ or K+ channel blockers (Gli/TEA). PFI-3 abolished Ca2+-induced contraction on endothelium-denuded mesenteric arteries preincubated by PE in Ca2+-free solution. Incubation with TG had no impact on PFI-3-induced vasorelaxation pre-contracted by PE. PFI-3 reduced Ca2+-induced contraction on endothelium-denuded mesenteric arteries pre-incubated by KCl (60 mM) in Ca2+-free solution. PFI-3 declined extracellular calcium influx in A10 cells detected by Fluo-3/AM fluorescent probe and fluorescence microscope. Furthermore, we observed that PFI-3 decreased the current densities of L-type VDCC by whole-cell patch clamp techniques. Conclusions: PFI-3 blunted PE and high K+-induced vasoconstriction independent of endothelium on rat mesenteric artery. The vasodilatory effect of PFI-3 may be attributed to its inhibition of VDCCs and receptor-operated calcium channels (ROCCs) on vascular smooth muscle cells (VSMCs).

Preparation of Naphthalenediimide-Decorated Electron-Deficient Photochromic Lanthanide (III)-MOF and Paper Strip as Multifunctional Recognition and Ratiometric Luminescent Turn-On Sensors for Amines and Pesticides.

Detecting toxic amine and pesticide contamination in the environment is one of the most pressing issues for environmental sustainability. In this work, two 3D Ln-BINDI complexes [Ln = Eu (1), Sm (2); H4BINDI (N, N'-bis(5-isophthalic acid)-1,4,5,8-naphthalenediimide)] have been designed and synthesized. Crystal structure of [Eu2(BINDI) (NO3)2(DMA)4]·2DMA (complex 1) featuring the lvt topology was determined by X-ray single-crystal diffraction. A multi-functional ratiometric luminescence sensor benefitting from π-electron-deficient NDI moieties and f-f transition characteristics of lanthanide Eu3+ ions for complex 1 has been investigated. Markedly, complex 1 exhibit completely different selective fluorescence ratiometric turn-on responses and pretty high sensitivity behaviors to aromatic amines (OPD), aliphatic amines (n-BA), and pesticides (TBZ), respectively, which are driven by interactions between the electron-donating amino group and acceptor NDI site, contributing to complex 1 as a potential ratiometric luminescent turn-on sensor for practical environmental applications. A PVA/1@paper strip can be used as a potential size selectivity sensor for the practical detection of aliphatic amine vapors in the environment through visual chromic fluorescence enhancement. Because NDIs can undergo one-electron reduction to form stable NDI· free radicals, solid complex 1 can visually distinguish different kinds of amines by selective amine-specific color changes and has the photochromic property of erasable inkless printing.

Prognosis after hepatic resection of patients with hepatocellular carcinoma related to non-alcoholic fatty liver disease: meta-analysis.

BACKGROUND: Whether the safety and efficacy of hepatic resection differ between patients whose hepatocellular carcinoma (HCC) is related to non-alcoholic fatty liver disease (NAFLD) or has other aetiologies is unknown. A systematic review was performed to explore potential differences between such conditions. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies that reported hazard ratios (HRs) for overall and recurrence-free survival between patients with NAFLD-related HCC or HCC of other aetiologies. RESULTS: The meta-analysis involved 17 retrospective studies involving 2470 patients (21.5 per cent) with NAFLD-related HCC and 9007 (78.5 per cent) with HCC of other aetiologies. Patients with NAFLD-related HCC were older and had higher body mass index (BMI), but were less likely to have cirrhosis (50.4 per cent versus 64.0 per cent, P < 0.001). The two groups suffered similar rates of perioperative complications and mortality. Patients with NAFLD-related HCC had slightly higher overall survival (HR 0.87, 95 per cent c.i. 0.75 to 1.02) and recurrence-free survival (HR 0.93, 95 per cent c.i. 0.84 to 1.02) than those with HCC of other aetiologies. In the various subgroup analyses, the only significant finding was that Asian patients with NAFLD-related HCC had significantly better overall survival (HR 0.82, 95 per cent c.i. 0.71 to 0.95) and recurrence-free survival (HR 0.88, 95 per cent c.i. 0.79 to 0.98) than Asian patients with HCC of other aetiologies. CONCLUSION: The available evidence suggests that patients with NAFLD-related HCC have similar perioperative complications and mortality, but potentially longer overall and recurrence-free survival, compared with those with HCC of other aetiologies. Tailored surveillance strategies should be developed for patients with NAFLD without cirrhosis.

miR-133a-3p/TRPM4 axis improves palmitic acid induced vascular endothelial injury.

Background: Vascular endothelial injury is a contributing factor to the development of atherosclerosis and the resulting cardiovascular diseases. One particular factor involved in endothelial cell apoptosis and atherosclerosis is palmitic acid (PA), which is a long-chain saturated fatty acid. In addition, transient receptor potential melastatin 4 (TRPM4), a non-selective cation channel, plays a significant role in endothelial dysfunction caused by various factors related to cardiovascular diseases. Despite this, the specific role and mechanisms of TRPM4 in atherosclerosis have not been fully understood. Methods: The protein and mRNA expressions of TRPM4, apoptosis - and inflammation-related factors were measured after PA treatment. The effect of TRPM4 knockout on the protein and mRNA expression of apoptosis and inflammation-related factors was detected. The changes of intracellular Ca2+, mitochondrial membrane potential, and reactive oxygen species were detected by Fluo-4 AM, JC-1, and DCFH-DA probes, respectively. To confirm the binding of miR-133a-3p to TRPM4, a dual luciferase reporter gene assay was conducted. Finally, the effects of miR-133a-3p and TRPM4 on intracellular Ca2+, mitochondrial membrane potential, and reactive oxygen species were examined. Results: Following PA treatment, the expression of TRPM4 increases, leading to calcium overload in endothelial cells. This calcium influx causes the assemblage of Bcl-2, resulting in the opening of mitochondrial calcium channels and mitochondrial damage, ultimately triggering apoptosis. Throughout this process, the mRNA and protein levels of IL-1ß, ICAM-1, and VCAM1 significantly increase. Database screenings and luciferase assays have shown that miR-133a-3p preferentially binds to the 3'UTR region of TRPM4 mRNA, suppressing TRPM4 expression. During PA-induced endothelial injury, miR-133a-3p is significantly decreased, but overexpression of miR-133a-3p can attenuate the progression of endothelial injury. On the other hand, overexpression of TRPM4 counteracts the aforementioned changes. Conclusion: TRPM4 participates in vascular endothelial injury caused by PA. Therefore, targeting TRPM4 or miR-133a-3p may offer a novel pharmacological approach to preventing endothelial injury.

Lower risk of hepatocellular carcinoma with tenofovir than entecavir treatment in subsets of chronic hepatitis B patients: an updated meta-analysis.

BACKGROUND AND AIM: Previous smaller meta-analyses comparing the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF) versus entecavir (ETV) provided controversial results. This updated meta-analysis aimed to reliably identify any difference in the HCC incidence between TDF-treated or ETV-treated CHB patients in general or in specific subgroups. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies with hazard ratios (HRs) for HCC between TDF-treated and ETV-treated CHB patients. Retrieved dates ranged from January 2009 to October 2021. HRs with or without adjustment were pooled with random-effects model. RESULTS: Twenty-four comparative studies involving 37 771 CHB patients treated with TDF and 72 094 treated with ETV were included. TDF was associated with lower risk of HCC compared with ETV, with pooled unadjusted HR of 0.76 (95% confidence interval [CI]: 0.67-0.86) (24 studies) and adjusted HR of 0.81 (95% CI: 0.72-0.91) (21 studies). In propensity score matching cohorts, the TDF superiority was confirmed for unadjusted HR 0.83 (95% CI: 0.71-0.97) (14 studies) and was close to significance for adjusted HR (0.78, 95% CI: 0.58-1.04) (8 studies). Subgroup analyses showed that TDF was associated with lower HCC risk than ETV treatment in CHB patients who were from Asia (adjusted HR: 0.76, 95% CI: 0.66-0.87; 15 studies) or nucleos(t)ide naïve (adjusted HR:0.74, 95% CI: 0.65-0.84; 18 studies). CONCLUSION: Current evidence from a sizable population suggests that TDF is associated with significantly lower HCC risk compared with ETV treatment in patients who are from Asia and/or nucleos(t)ide naïve.

The modulation of salience and central executive networks by acute stress in healthy males: An EEG microstates study.

EEG microstate analysis involves the examination of topographies of the scalp potential fields to indicate the temporal dynamics of resting-state networks on a millisecond time scale, through which we can investigate the subsecond brain dynamics of stress in individuals. The present study implemented the EEG microstate method to explore the temporal dynamic changes of the large-scale brain networks induced by acute stress. The participants (n = 51) were randomly exposed to a stress condition (n = 25) (induced by Trier Social Stress Test, TSST) or a control condition (n = 26). Two 4-min blocks of resting EEG data were recorded before and after the stress/control test to reflect the stress effect on temporal dynamics of EEG microstates. The results showed that the stress group had larger occurrences and coverage of microstate class C during the post-test session than during the pre-test session. This pattern was reversed in the control group. Further, the microstate class C showed positive correlations with negative affect and perceived stress levels following acute stress. The transition probability between the microstates C and D was larger during the post-test session than during the pre-test session in the stress group, but not different in the control group. In addition, the microstate pairs C and D were positively correlated with negative affect and perceived stress levels. The proportion and sequence of EEG microstates class C and D reflected deviations of salience and executive functions following acute stress. We further proposed that the coordination between salience and executive functions was promoted by acute stress.

Cu-MOF Material Constructed with a Triazine Polycarboxylate Skeleton: Multifunctional Identify and Microdetecting of the Aromatic Diamine Family (o,m,p-Phenylenediamine) Based on the Luminescent Response.

Organic aromatic amines are widely used in various fields such as pharmaceuticals, pesticides, dyes, and tobacco smoke. The pollution of organic amines has become a problem that cannot be ignored, due to the extensive harmful effects on the environment and public health, which has become one of the most concerned frontier fields in the world. Identifying and microdetecting o-phenylenediamine (OPD), m-phenylenediamine (MPD), and p-phenylenediamine (PPD) using MOFs have rarely been reported. On the basis of the blue emission properties of Cu-TBDA constructed with 5,5'-((6-chloro-1,3,5-triazine-2,4-diyl)bis(azanediyl))diisophthalic acid (H4TBDA) ligand, Cu-TBDA was studied primarily to identify and detect aromatic diamine family as a multifunctional chemical sensor. Interestingly, Cu-TBDA has a very high selectivity and sensitivity to OPD and MPD with a low limit of detection (5.00 µM for OPD and 1.77 µM for MPD). Especially for OPD, Cu-TBDA has a unique switching function for it. When the concentration of OPD is less than 9.1 × 10-4 M, the fluorescence response of Cu-TBDA suspension exhibit enhanced. However, when the concentration of OPD is more than 9.1 × 10-4 M, the emission intensity displays quenching phenomenon. Therefore, Cu-TBDA as a chemical sensor not only has recognition and detection functions for organic aromatic amines but also first exhibits turn-on and -off sensing behavior toward OPD.

Outcomes of Liver Resection for Metabolic Dysfunction-Associated Fatty Liver Disease or Chronic Hepatitis B-Related HCC.

AIMS: This study aims to determine differences in severity of background liver disease at hepatocellular carcinoma (HCC) diagnosis and long-term survival outcomes among patients undergoing liver resection for HCC in the background of metabolic dysfunction-associated fatty liver disease (MAFLD) compared to chronic hepatitis B (CHB) alone or concurrent CHB (CHB/MAFLD). METHODS: Patient demographics and comorbidities, clinicopathologic data, perioperative and long-term outcomes among patients who underwent liver resection for HCC were reviewed. Overall and recurrence-free survival were calculated with the Kaplan-Meier method, with the values compared using the log-rank test. RESULTS: From January 2014 to December 2018, 1325 patients underwent potential curative liver resection of HCC; 67 (5.0%), 176 (13.3%), and 1082 (81.7%) patients had MAFLD alone, CHB concurrent with MAFLD, and CHB alone, respectively. At HCC diagnosis, fewer MAFLD patients had cirrhosis, alpha fetoprotein concentration ≥ 400 ng/mL, tumor size ≥ 5 cm, mulinodular, microvascular invasion, receiving major hepatectomy, and receiving adjuvant transarterial chemoembolization. After a median follow-up of 47 months after liver resection, MAFLD (or MAFLD plus CHB/MAFLD) patients had significantly higher overall and recurrence-free survival than CHB patients before or after propensity score analysis (all P<0.05). CONCLUSION: Patients with HCC in the setting of MAFLD have less-severe background liver disease at HCC diagnosis and better long-term survival after curative liver resection compared to counterparts with CHB/MAFLD or CHB.

Analysis of Clinicopathological Characteristics and Prognosis of Young Patients with Hepatocellular Carcinoma after Hepatectomy.

Background and Aims: This study was designed to analyze the effects of age and clinicopathological characteristics on prognosis of Chinese patients with hepatocellular carcinoma (HCC). Methods: The clinical data of 2032 HCC patients who were first diagnosed with HCC and underwent curative hepatectomy in our hospital between January 2006 and January 2011 were retrospectively analyzed. Results: Younger HCC patients (age <40 years, n=465) had a significantly higher hepatitis B infection rate, larger tumors, higher alpha-fetoprotein levels, higher preoperative liver function, and more frequent vascular invasions than older patients. Most younger patients were suitable for anatomical hepatectomy, and their tumors were found to be at a highly advanced stage. The recurrence-free survival and overall survival rates of younger HCC patients were significantly worse than those of older patients but this difference disappeared after propensity score matching. Multivariate analysis of pre-matched samples showed that age ≤40 years was one of the independent risk factors associated with poor overall survival. Conclusions: Younger patients showed different clinicopathological characteristics than older patients, such as higher rates of hepatitis B infection and advanced tumors. The recurrence-free survival and overall survival rates of younger HCC patients after hepatectomy may be similar to those of older patients.

Development and validation of a nomogram for assessing survival in patients with hepatocellular carcinoma after hepatectomy.

BACKGROUND AND AIM: Assessing the average survival rate of patients with hepatocellular carcinoma (HCC) after hepatectomy is important for making critical decisions in everyday clinical practice. The present study aims to develop and validate a nomogram for assessing the overall survival probability for such patients. METHODS: The putative prognostic indicators for constructing the nomogram were identified using multivariable Cox regression and model selection based on the Akaike information criterion. The nomogram was subjected to internal and external validation. The nomogram endpoints were death within 1, 3, and 5 years. RESULTS: A consecutive sample of 522 HCC patients who underwent potentially curative hepatectomy was retrospectively analyzed. Age, Barcelona clinic liver cancer (BCLC) stage, tumor size, alanine transaminase, alpha fetal protein, and serum prealbumin were included in the final model. The nomogram's discriminative ability was good in the training set (C-index was 0.74 for 1 year, 0.73 for 3 years, 0.70 for 5 years) and was validated using both an internal bootstrap method (C-index was 0.73 for 1 year, 0.72 for 3 years, 0.69 for 5 years) and an external validating set (C-index was 0.72 for 1 year, 0.72 for 3 years, 0.69 for 5 years). The calibration plots for the endpoints showed optimal agreement between the nomogram's assessment and actual observations. CONCLUSIONS: The nomogram (an Excel-based tool) can be useful for assessing the probability of survival at 1, 3, and 5 years in patients with HCC after hepatectomy.