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.

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.

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.

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.

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.

Correlation between serum prealbumin and prognosis of patients with hepatocellular carcinoma after hepatectomy.

OBJECTIVE: To determine whether serum prealbumin levels are associated with long-term survival after hepatectomy in patients with primary hepatocellular carcinoma(HCC). METHODS: A consecutive sample of 526 patients with HCC who underwent potentially curative hepatectomy from August 2007 to August 2010 was retrospectively analyzed. Patients were classified as having normal or reduced serum prealbumin based on cut-off values of 200 or 182 mg/L. RESULTS: Multivariate analysis identified the preoperative level of serum prealbumin as an independent prognostic factor of long-term survival (P < 0.05): Survival was significantly better for those with normal levels than for those with reduced levels, based on either cut-off value. Similar results were observed in subgroup analyses based on the degree of cirrhosis, level of ɑ-fetoprotein and Barcelona Clinic Liver Cancer stage. CONCLUSIONS: Preoperative level of serum prealbumin may be useful for predicting long-term survival in patients with HCC after hepatectomy.

Pharmacological inhibition of SUMO-1 with ginkgolic acid alleviates cardiac fibrosis induced by myocardial infarction in mice.

BACKGROUND AND PURPOSE: Protein modification by small ubiquitin-like modifier (SUMO) plays a critical role in the pathogenesis of heart diseases. The present study was designed to determine whether ginkgolic acid (GA) as a SUMO-1 inhibitor exerts an inhibitory effect on cardiac fibrosis induced by myocardial infarction (MI). EXPERIMENTAL APPROACH: GA was delivered by osmotic pumps in MI mice. Masson staining, electron microscopy (EM) and echocardiography were used to assess cardiac fibrosis, ultrastructure and function. Expression of SUMO-1, PML, TGF-ß1 and Pin1 was measured with Western blot or Real-time PCR. Collagen content, cell viability and myofibroblast transformation were measured in neonatal mouse cardiac fibroblasts (NMCFs). Promyelocytic leukemia (PML) protein was over-expressed by plasmid transfection. KEY RESULTS: GA improved cardiac fibrosis and dysfunction, and decreased SUMO-1 expression in MI mice. GA (>20 µM) inhibited NMCF viability in a dose-dependent manner. Nontoxic GA (10 µM) restrained angiotensin II (Ang II)-induced myofibroblast transformation and collagen production. GA also inhibited expression of TGF-ß1 mRNA and protein in vitro and in vivo. GA suppressed PML SUMOylation and PML nuclear body (PML-NB) organization, and disrupted expression and recruitment of Pin1 (a positive regulator of TGF-ß1 mRNA), whereas over-expression of PML reversed that. CONCLUSIONS AND IMPLICATIONS: Inhibition of SUMO-1 by GA alleviated MI-induced heart dysfunction and fibrosis, and the SUMOylated PML/Pin1/TGF-ß1 pathway is crucial for GA-inhibited cardiac fibrosis.

Bacillomycin D Produced by Bacillus amyloliquefaciens Is Involved in the Antagonistic Interaction with the Plant-Pathogenic Fungus Fusarium graminearum.

Fusarium graminearum (teleomorph: Ascomycota, Hypocreales, Gibberella, Gibberella zeae) is a destructive fungal pathogen that threatens the production and quality of wheat and barley worldwide. Controlling this toxin-producing pathogen is a significant challenge. In the present study, the commercially available strain Bacillus amyloliquefaciens (Bacteria, Firmicutes, Bacillales, Bacillus) FZB42 showed strong activity against F. graminearum The lipopeptide bacillomycin D, produced by FZB42, was shown to contribute to the antifungal activity. Purified bacillomycin D showed strong activity against F. graminearum, and its 50% effective concentration was determined to be approximately 30 µg/ml. Analyses using scanning and transmission electron microscopy revealed that bacillomycin D caused morphological changes in the plasma membranes and cell walls of F. graminearum hyphae and conidia. Fluorescence microscopy combined with different dyes showed that bacillomycin D induced the accumulation of reactive oxygen species and caused cell death in F. graminearum hyphae and conidia. F. graminearum secondary metabolism also responded to bacillomycin D challenge, by increasing the production of deoxynivalenol. Biological control experiments demonstrated that bacillomycin D exerted good control of F. graminearum on corn silks, wheat seedlings, and wheat heads. In response to bacillomycin D, F. graminearum genes involved in scavenging reactive oxygen species were downregulated, whereas genes involved in the synthesis of deoxynivalenol were upregulated. Phosphorylation of MGV1 and HOG1, the mitogen-activated protein kinases of F. graminearum, was increased in response to bacillomycin D. Taken together, these findings reveal the mechanism of the antifungal action of bacillomycin D.IMPORTANCE Biological control of plant disease caused by Fusarium graminearum is desirable. Bacillus amyloliquefaciens FZB42 is a representative of the biocontrol bacterial strains. In this work, the lipopeptide bacillomycin D, produced by FZB42, showed strong fungicidal activity against F. graminearum Bacillomycin D caused morphological changes in the plasma membrane and cell wall of F. graminearum, induced accumulation of reactive oxygen species, and ultimately caused cell death in F. graminearum Interestingly, when F. graminearum was challenged with bacillomycin D, the deoxynivalenol production, gene expression, mitogen-activated protein kinase phosphorylation, and pathogenicity of F. graminearum were significantly altered. These findings clarified the mechanisms of the activity of bacillomycin D against F. graminearum and highlighted the potential of B. amyloliquefaciens FZB42 as a biocontrol agent against F. graminearum.

Bone morphogenetic protein-2 antagonizes bone morphogenetic protein-4 induced cardiomyocyte hypertrophy and apoptosis.

Our previous work showed that the expression of bone morphogenetic protein-4 (BMP4) was up-regulated in pathological cardiac hypertrophy models and BMP4 induced cardiomyocyte hypertrophy and apoptosis. Bone morphogenetic protein-2 (BMP2) and BMP4 share greater than 80% amino acid homology and there exists an interaction between BMP2 and BMP4, so the aim of the present study was to elucidate the changes of BMP2 in the cardiac hypertrophy models and the effects of BMP2 on BMP4-induced cardiomyocyte hypertrophy and apoptosis. The in vivo cardiac hypertrophy models were induced by pressure-overload and swimming exercise in mice. BMP2 mRNA and protein expressions increased in pressure-overload and swimming-exercise induced cardiac hypertrophy. BMP2 itself did not elicit cardiomyocyte hypertrophy and apoptosis, but antagonized BMP4-induced cardiomyocyte hypertrophy and apoptosis. BMP2 stimulated Akt in cardiomyocytes and Akt inhibitor prevented the antagonism of BMP2 on BMP4-induced cardiomyocyte apoptosis. Furthermore, BMP2 inhibited BMP4-induced JNK activation in cardiomyocytes. In conclusion, BMP2 antagonizes BMP4-induced cardiomyocyte hypertrophy and apoptosis. The anti-apoptotic effects of BMP2 on BMP4-induced cardiomyocyte apoptosis might be through activating Akt and inhibiting JNK activation.

Interacting and joint effects of triglyceride-glucose index and hypertension on stroke risk in middle-aged and older Chinese adults: a population-based prospective cohort study.

Background: Triglyceride-glucose (TyG) index and hypertension were well-established risk factors for stroke. And TyG index was associated with hypertension. However, no prior study has investigated the interactive effects of the TyG index and hypertension on stroke. This study examined whether hypertension mediates associations of TyG index with incident stroke and the extent of interaction or joint relations of TyG index and hypertension with stroke in middle-aged and older Chinese adults. Methods: The China Health and Retirement Longitudinal Study (CHARLS) is an ongoing nationally representative prospective cohort study initiated in 2011. This cohort study included 9,145 middle-aged and older Chinese adults without stroke at baseline. The eposures were TyG index and the logarithmized product of hypertension, as determined during the baseline health examination. The main outcome was self-reported physician-diagnosed stroke which followed up from June 1, 2011, to June 30, 2018. Results: Of the 9,145 participants, 4,251 were men (46.5%); the mean (SD) age was 59.20 (9.33) years. During a median follow-up of 7.1 years, 637 (7.0%) participants developed stroke. In multivariable-adjusted models, the TyG index was significantly associated with the risk of hypertension [odds ratio (OR) per 1-SD increase, 1.29; 95% CI, 1.19-1.41] and stroke [hazard ratio (HR) per 1-SD increase, 1.16; 95% CI, 1.02-1.33]. Both multiplicative and additive interactions were observed between TyG index and hypertension on stroke (HR for multiplicative: 2.34, 95% CI, 1.57-3.48; Synergy index: 4.13, 95% CI, 2.73-6.25). Mediation analysis showed that 20.0% of the association between TyG index and stroke was mediated through hypertension. Conclusions: This study suggests a synergistic effect of TyG index and hypertension on stroke, and a small proportion of the association between TyG index and stroke was mediated by hypertension, indicating the benefit of coordinated control strategies for both exposures.

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.

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.

Copper induces vasorelaxation and antagonizes noradrenaline-induced vasoconstriction in rat mesenteric artery.

BACKGROUND/AIMS: Copper is an essential trace element for normal cellular function and contributes to critical physiological or pathological processes. The aim of the study was to investigate the effects of copper on vascular tone of rat mesenteric artery and compare the effects of copper on noradrenaline (NA) and high K(+) induced vasoconstriction. METHODS: The rat mesenteric arteries were isolated and the vessel tone was measured by using multi wire myograph system in vitro. Blood pressure of carotid artery in rabbits was measured by using physiological data acquisition and analysis system in vivo. RESULTS: Copper dose-dependently blunted NA-induced vasoconstriction of rat mesenteric artery. Copper-induced vasorelaxation was inhibited when the vessels were pretreated with NG-nitro-L-arginine methyl ester (L-NAME). Copper did not blunt high K(+)-induced vasoconstriction. Copper preincubation inhibited NA-evoked vasoconstriction and the inhibition was not affected by the presence of L-NAME. Copper preincubation showed no effect on high K(+)-evoked vasoconstriction. Copper chelator diethyldithiocarbamate trihydrate (DTC) antagonized the vasoactivity induced by copper in rat mesenteric artery. In vivo experiments showed that copper injection (iv) significantly decreased blood pressure of rabbits and NA or DTC injection (iv) did not rescue the copper-induced hypotension and animal death. CONCLUSION: Copper blunted NA but not high K(+)-induced vasoconstriction of rat mesenteric artery. The acute effect of copper on NA-induced vasoconstriction was depended on nitric oxide (NO), but the effect of copper pretreatment on NA-induced vasoconstriction was independed on NO, suggesting that copper affected NA-induced vasoconstriction by two distinct mechanisms.

Bone morphogenetic protein-4 contributes to the down-regulation of Kv4.3 K+ channels in pathological cardiac hypertrophy.

Kv4.3 K(+) channels contributing to Ito are involved in the repolarization of cardiac action potential. Kv4.3 K(+) channels decrease in pathological cardiac hypertrophy, but the mechanism remains unclear. Our previous study found that the expression of bone morphogenetic protein 4 (BMP4) increased in pressure-overload and Ang II constant infusion induced cardiac hypertrophy. Since the downregulation of Kv4.3 K(+) channels and the upregulation of BMP4 simultaneously occur in pathological cardiac hypertrophy, we hypothesize that the up-regulated BMP4 would contribute to the downregulation of Kv4.3 K(+) channels in cardiac hypertrophy. We found that BMP4 treatment reduced Kv4.3 but not Kv4.2 and Kv1.4 K(+) channel protein expression, and BMP4-induced decrease of Kv4.3 K(+) channel protein expression was reversed by BMP4 inhibitor noggin and DMH1 in cultured cardiomyocytes in vitro. BMP4-induced decrease of Kv4.3 K(+) channel protein expression was also reversed by the NADPH oxidase inhibitor apocynin and the radical scavenger tempol. In in vivo transverse aortic constriction (TAC)-induced cardiac hypertrophy, constant infusion of DMH1 completely rescued TAC-induced down-regulation of Kv4.3 K(+) channel protein expression. We conclude that BMP4 contributes to the downregulation of Kv4.3 K(+) channels in pathological cardiac hypertrophy and the underlying mechanism might be through increasing ROS production.

Upregulation of M3 muscarinic receptor inhibits cardiac hypertrophy induced by angiotensin II.

BACKGROUND: M3 muscarinic acetylcholine receptor (M3-mAChR) is stably expressed in the myocardium, but its pathophysiological role remains largely undefined. This study aimed to investigate the role of M3-mAChR in cardiac hypertrophy induced by angiotensin II (Ang II) and elucidate the underlying mechanisms. METHODS: Cardiac-specific M3-mAChR overexpression transgenic (TG) mice and rat H9c2 cardiomyoblasts with ectopic expression of M3-mAChR were established. Models of cardiac hypertrophy were induced by transverse aortic constriction (TAC) or Ang II infusion in the mice in vivo, and by isoproterenol (ISO) or Ang II treatment of H9c2 cells in vitro. Cardiac hypertrophy was evaluated by electrocardiography (ECG) measurement, hemodynamic measurement and histological analysis. mRNA and protein expression were detected by real-time RT-PCR and Western blot analysis. RESULTS: M3-mAChR was upregulated in hypertrophic heart, while M2-mAChR expression did not change significantly. M3-mAChR overexpression significantly attenuated the increased expression of atrial natriuretic peptide and ß-myosin heavy chain induced by Ang II both in vivo and in vitro. In addition, M3-mAChR overexpression downregulated AT1 receptor expression and inhibited the activation of MAPK signaling in the heart. CONCLUSION: The upregulation of M3-mAChR during myocardial hypertrophy could relieve the hypertrophic response provoked by Ang II, and the mechanism may involve the inhibition of MAPK signaling through the downregulation of AT1 receptor.

Large T-antigen up-regulates Kv4.3 K⁺ channels through Sp1, and Kv4.3 K⁺ channels contribute to cell apoptosis and necrosis through activation of calcium/calmodulin-dependent protein kinase II.

Down-regulation of Kv4.3 K⁺ channels commonly occurs in multiple diseases, but the understanding of the regulation of Kv4.3 K⁺ channels and the role of Kv4.3 K⁺ channels in pathological conditions are limited. HEK (human embryonic kidney)-293T cells are derived from HEK-293 cells which are transformed by expression of the large T-antigen. In the present study, by comparing HEK-293 and HEK-293T cells, we find that HEK-293T cells express more Kv4.3 K⁺ channels and more transcription factor Sp1 (specificity protein 1) than HEK-293 cells. Inhibition of Sp1 with Sp1 decoy oligonucleotide reduces Kv4.3 K⁺ channel expression in HEK-293T cells. Transfection of pN3-Sp1FL vector increases Sp1 protein expression and results in increased Kv4.3 K⁺ expression in HEK-293 cells. Since the ultimate determinant of the phenotype difference between HEK-293 and HEK-293T cells is the large T-antigen, we conclude that the large T-antigen up-regulates Kv4.3 K⁺ channel expression through an increase in Sp1. In both HEK-293 and HEK-293T cells, inhibition of Kv4.3 K⁺ channels with 4-AP (4-aminopyridine) or Kv4.3 small interfering RNA induces cell apoptosis and necrosis, which are completely rescued by the specific CaMKII (calcium/calmodulin-dependent protein kinase II) inhibitor KN-93, suggesting that Kv4.3 K⁺ channels contribute to cell apoptosis and necrosis through CaMKII activation. In summary, we establish: (i) the HEK-293 and HEK-293T cell model for Kv4.3 K⁺ channel study; (ii) that large T-antigen up-regulates Kv4.3 K⁺ channels through increasing Sp1 levels; and (iii) that Kv4.3 K⁺ channels contribute to cell apoptosis and necrosis through activating CaMKII. The present study provides deep insights into the mechanism of the regulation of Kv4.3 K⁺ channels and the role of Kv4.3 K⁺ channels in cell death.

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.

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.