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Objective: To clarify the anti-depressive potential mechanisms of Kaixin Powder (KP), a drug that helps to prevent and treat depression and other mentaldiseases, from genome-wide transcriptome profiling., Methods: Transcriptome and KEGG pathway analysis were conducted on the hippocampus of depressed rats, then the differentially expressed genes were validated and serum concentration of lipid parameters were identified by enzymatic assays. Furthermore, high-fat diets induced depression-like behaviors in Syrian golden hamsters were conducted to verify the predicted molecular mechanisms acquired from the transcriptome analysis., Results: Transcriptome results revealed that the 24 differentially expressed genes (DEGs) in chronic mild stress (CMS) rats could be reversed after two weeks of KP treatment. The mechanisms of KP in treating depression firstly involved the regulation of several pathology modules, including lipid metabolism, synapse function and inflammation. KP could regulate imbalances of lipid homeostasis in high-fat diet induced depressive symptoms. Furthermore, it was validated that cholesterol metabolism dysfunction can be ameliorated by KP, which was correlated with upregulation of the AdipoR1-BDNF (brain-derived neurotrophic factor) co-regulatory pathway., Conclusion: Taken together, our results demonstrated that KP not only alleviates depression via traditional mental illness targets, but it may also simulates the cholesterol metabolism and adiponectin signaling with multi-target characteristics., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Efficient uptake to both cytoplasm and nucleus in live cells remains a key obstacle for G-quadruplex targeting fluorophores. We developed a Pt(IV) complex by oxidizing a bisphenanthrolinyl Pt(II) complex, which is our first generation G-quadruplex specific fluorogenic probe. 15 The axial lipophilic ligand assists Pt(IV) pro-probe to enter live cells and reach the nucleus rapidly. In situ reduction of Pt(IV) pro-probe restores parental Pt(II) complex, and sequentially lights up both RNA and DNA G-quadruplexes in live cancerous cells simultaneously. Pt(IV) pro-probe shows potent cytotoxicity after long time incubation as a dual-functional theranostic agent., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background & Aims: Previous research established that the availability of l-arginine affects placental vascular development and fetal growth. However, practical details associated with the effects of l-arginine supplementation on the neonatal outcomes of hypertensive disorder (HD) and intrauterine growth restriction (IUGR) pregnancies are limited., Methods: The PubMed, ScienceDirect, and Web of Science databases were searched for peer-reviewed literature published by September 30, 2021 to investigate the operational details of l-arginine supplementation in improving neonatal outcomes in complicated pregnancies. Standardized mean difference (SMD) and weighted mean difference (WMD) of continuous variables, as well as the risk ratio (RR) for categorical variables were pooled by random-effects models., Results: The results indicated that l-arginine supplementation increased the plasma nitric oxide (NO) concentrations in IUGR pregnancies (SMD: 0.71; 95% CI: 0.45, 0.97; I 2  = 0%), but decreased the risk of preeclampsia in HD mothers (RR: 0.49; 95% CI: 0.31, 0.76; I 2  = 0%). Administration with l-arginine elevated birth weights both in hypertensive and IUGR pregnant women, with WMDs of 194.70 g (95% CI: 58.21, 331.20; I 2  = 44.2%) and 134.00 g (95% CI: 43.53, 224.46; I 2  = 42.4%), respectively. However, the intervention had no effect on gestational age except in HD pregnancies (WMD: 7.05 d; 95% CI: 3.16, 10.95; I 2  = 36.5%). l-arginine administration during pregnancy significantly reduced the small for gestational age (SGA) risk of fetus both in HD (RR: 0.51; 95% CI: 0.31, 0.83; I 2  = 0.0%) and IUGR mothers (RR: 0.46; 95% CI: 0.25, 0.88; I 2  = 0.0%). Subgroup analyses revealed that l-arginine supplementation at <4 g/d dosage or for ≥1-month duration or in the third trimester had a greater effect on birth weights in HD women without proteinuria, but a higher l-arginine dosage was more beneficial for extending gestational age and reducing the risk of SGA in older pregnancies. Additionally, intravenous infusion of l-arginine, but not oral administration, significantly increased birth weight in IUGR pregnancies with elevated NO concentrations, although the recommended amount should be confined to <4 g/d., Conclusions: These findings provide practical guidelines for l-arginine supplementation to improve the birth outcomes of complicated pregnancies., Registry Number: CRD42021246290 (https://www.crd.york.ac.uk/PROSPERO)., Competing Interests: Conflicts of Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Serum Helicobacter pylori (H. pylori) antibody kits (LZ and LIA) using the latex agglutination immunoassay method are commercially available, but few studies have been performed to determine their diagnostic accuracy or to compare their results with those of enzyme-linked immunosorbent assay (ELISA) kits (EP and EIA)., Methods: Sera were obtained from 213 hospital outpatients with dyspeptic symptoms. The serological results were compared with the result of the 13 C-urea breath test (UBT) which seems to be reliable., Results: Of the 213 subjects, 154 were diagnosed as positive for H. pylori infection according to the UBT. The sensitivities and specificities of these tests were 97.4% and 76.3%, 98.1% and 78.0%, 99.4% and 74.6%, and 98.1% and 71.2% for the EP, LZ, EIA and LIA tests, respectively. When the 13 subjects whose seropositive results of the four kits were completely opposite to the negative results of the UBT were excluded, the specificities of evaluated kits were all higher than 90%. The concordance rate between the EP and EIA tests was 98.1% (Spearman's rank correlation coefficient = 0.83) and that between the LZ and LIA tests was 97.1% (correlation coefficient = 0.91). The LZ gave higher antibody titer value than EP (p < 0.0001, Z = 9.82; Wilcoxon signed-rank test), and EIA gave higher value than LIA (p < 0.0001, Z = 6.43; Wilcoxon signed-rank test)., Conclusions: The latex immunoassay method provided the same reliability to ELISA in terms of the diagnostic accuracy for current H. pylori infection, although we should take into account the titer value differences by each test method in practical use., (Copyright © 2019. Published by Elsevier Ltd.)

Transcriptional enhancers play a key role in cell type-specific gene expression and cell fate transition. Enhancers are marked by histone H3K4 mono- and di-methylation (H3K4me1/2). The tumor suppressor MLL4 (KMT2D) is a major enhancer H3K4 mono- and di-methyltransferase with a partial functional redundancy with MLL3 (KMT2C). However, the functional role of MLL4 enzymatic activity remains elusive. To address this issue, we have generated MLL4 enzyme-dead knock-in (KI) embryonic stem (ES) cells and mice, which carry Y5477A/Y5523A/Y5563A mutations in the enzymatic SET domain of the MLL4 protein. Homozygous MLL4 enzyme-dead KI (Mll4 KI/KI ) mice are embryonic lethal and die around E10.5, which phenocopies Mll4 knockout mice. Interestingly, enzyme-dead MLL4 protein in ES cells is highly unstable. Like Mll4 knockout ES cells, Mll4 KI/KI ES cells show reduced levels of H3K4me1/2. Furthermore, we show that ectopic expression of histone H3.3 lysine 4-to-methionine (K4M) mutant, which reduces endogenous H3K4 methylation levels in ES cells, decreases the protein stability of MLL3 and MLL4 but not that of H3K4 methyltransferases SET1A (KMT2F) and SET1B (KMT2G). Taken together, our findings indicate that MLL4 protein stability is tightly regulated by its H3K4 methyltransferase activity., (Published by Elsevier Ltd.)

Background and Aims: Coronary heart disease (CHD) and stroke have common risk factors, but some of these differ in the magnitude or direction of associations between CHD and stroke. We assessed whether the impact of each risk factor differed between CHD and stroke mortality in Asians., Methods: In total, 104 910 subjects aged 40-79 years without histories of cancer, CHD and stroke at baseline were followed between 1988 and 2009. Competing-risks analysis was used to test for differences in the associations of each risk factor with two endpoints (CHD and stroke). Population attributable fractions (PAFs) were also calculated for these endpoints to estimate the population impact of each risk factor., Results: During a median 19.1-year follow-up, 1554 died from CHD and 3163 from stroke. The association of hypertension with CHD was similar to that with stroke in terms of the magnitude and direction (multivariable-adjusted hazard ratio for CHD: 1.63 vs. stroke: 1.73 in men and 1.70 vs. 1.66 in women). Conversely, the magnitude of these associations differed for smoking (CHD: 1.95 vs. stroke: 1.23 in men and 2.45 vs. 1.35 in women) and diabetes (1.49 vs. 1.09 in men and 2.08 vs. 1.39 in women). The highest PAF for CHD was caused by smoking in men and by hypertension in women; that for stroke was caused by hypertension in both sexes., Conclusions: Hypertension associations and PAFs were consistent between CHD and stroke, but not for other risk factors. These findings may be useful to optimize public health intervention strategies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In this report, an ultrasensitive electrochemical biosensor for miR-21 detection was designed on the basis of a padlock exponential rolling circle amplification (P-ERCA) assay and CoFe 2 O 4 magnetic nanoparticles (CoFe 2 O 4 MNPs) by nanoelectrocatalysis without a substrate for signal amplification. Here, to improve catalytic efficiency, nanocatalyst (CoFe 2 O 4 MNPs) and redox molecule (Tb) were co-immobilized onto the graphene (Gra) surface and formed Au@CoFe 2 O 4 /Tb-Gra probe. The obtained probe exhibits high-performance Tb catalysis by reducing the interaction distance between CoFe 2 O 4 MNPs and Tb, and importantly, the detection sensitivity is significantly improved even in the absence of substrate (H 2 O 2 ). Simultaneously, to further improve the sensitivity and specificity of the biosensor, P-ERCA assay was introduced. After multiple polymerization and nicking reactions, plenty of P-ERCA amplification product was produced and circular exponential signal amplification was achieved, giving an extreme sensitivity for miR-21 assay. The as-prepared biosensor shows a wide dynamic range of 1 fM to 2 nM with a low detection limit of 0.3 fM for miR-21 detection and exhibits high specificity and sensitivity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: The extremely high incidence of esophageal cancer in certain rural areas of China has prompted significant intellectual curiosity and research efforts both in China and abroad., Methods: We summarize the research progress over the past several decades in high-risk areas (Linxian, Cixian, Shexian, and Yanting) based on literature research and our field trip (2012-2013)., Results: Considerable progress in clarifying the environmental risk factors and pathogenesis of esophageal cancer in high-risk areas has been achieved over the past several decades. Epidemiologic evidence suggests that carcinogen exposure and nutritional deficiency, rather than smoking and drinking, may be the major risk factors for esophageal cancer in the Taihang Mountains region, where the incidence of esophageal cancer is among the highest in the world. Two genome-wide association studies have identified variants in PLCE1 at 10q23 that are significantly associated with esophageal cancer risk. Recent whole-exome studies have revealed a comprehensive mutation pattern, in which the C>T transition is the predominant mutation type., Conclusions: Despite extensive research, the main causative factors that contribute to esophageal cancer in high-risk areas have not yet been elucidated. Challenges in this research area include determining the causative role of nitrosamine, identifying other potential carcinogens, and conducting fruitful international collaborative studies based on a multidisciplinary approach. Increased international collaboration will contribute to a better understanding of the etiology of esophageal cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: To examine the association of intrahepatic fat with homeostasis model assessment-insulin resistance (HOMA-IR), a marker of insulin resistance, in Japanese adults, and whether intrahepatic fat is associated with insulin resistance independent of waist circumference and other measures of obesity., Methods: Fifty-three individuals aged 37-69 were studied. Spectrum obtained using a 3-T magnetic resonance imager was analysed with LCModel to quantify intrahepatic fat. Blood levels of insulin, glucose and other biochemical markers were obtained after 8h or more fasting. Percent body fat was estimated by a bioelectrical impedance analyzer. HOMA-IR and intrahepatic fat content were log-transformed in the analysis., Results: We found a positive correlation between intrahepatic fat and HOMA-IR, which was independent of the anthropometric measures of obesity. In contrast, significant and positive correlations of body mass index, percent body fat, and waist circumference with HOMA-IR were largely explained by their associations with intrahepatic fat. Intrahepatic fat was positively associated with alanine transaminase and triglycerides even after adjustment for HOMA-IR., Conclusion: Intrahepatic fat was associated with insulin resistance independent of age, sex, and measures of obesity in Japanese adults. Hypertriglyceridemia and liver injury may directly occur subsequent to intrahepatic fat accumulation., (Copyright © 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)