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Yuan-Zhen Lin, Xiao-Ning Zhong, Xin Chen, Yi Liang, Hui Zhang, Dong-Lan Zhu Department of Respiratory Medicine, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Xiao-Ning ZhongDepartment of Respiratory Medicine, The First Affiliated Hospital, Guangxi Medical University, No. 6, Shuangyong Road, Nanning, Guangxi 530021 People’s Republic of ChinaTel +86 771 535 1176Fax +86 771 535 1176Email xnzhong101@sina.comPurpose: To explore the potential mechanism underpinning the development of chronic obstructive pulmonary disease (COPD) and to investigate the role of the Roundabout signaling pathway in COPD.Methods: Three microarray datasets (GSE1650, GSE38974 and GSE76925) including 139 cases of severe COPD and 52 cases of normal smokers without carcinoma, were integrated to screen differentially expressed genes (DEGs) using bioinformatics methods. Gene ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the DEGs were performed by a DAVID online tool. Finally, a cigarette smoke (CS)- induced emphysema mice model was established, the lung mRNA expression levels of genes associated with Slit guidance ligand 2 (SLIT2) -Roundabout (ROBO) signaling pathway were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR), and the protein level of SLIT2 was examined by immunohistochemistry staining.Results: A total of 315 DEGs were identified in three databases. GO and KEGG pathway analyses suggested that the inflammatory response, extracellular matrix disassembly, immune response, the apoptotic signaling pathway, ubiquitination and the Roundabout signaling pathway all together were involved in the development of COPD. The genes SLIT2 and ROBO2 were decreased in patients with COPD and these decreases were significantly negatively correlated with the disease stages of COPD. Consistently, the mRNA expression levels of SLIT2, ROBO1 and ROBO2, and the protein level of SLIT2 were revealed to be lower in the lungs of CS-induced emphysema mice compared with the air-exposed control mice. In addition, the SLIT2 protein level was negatively associated with alveolar mean linear intercept.Conclusion: Integrated bioinformatics analysis may provide novel insights into the complicated pathogenesis of COPD, and to the best of our knowledge, this study is the first to provide evidence to suggest that the Roundabout signaling pathway may be involved in the pathogenesis of COPD.Keywords: chronic obstructive pulmonary disease, GEO database, roundabout signaling pathway, SLIT2, ROBO

This paper introduces new classes of generalized invex monotone mappings and invex cocoercive mappings. Their differential property and role to analyze and solve variational-like inequality problem are presented.

Quantum dots (QDs) exhibit superior brightness and photochemical stability, making them the preferred option for highly sensitive single-molecule detection compared with fluorescent dyes or proteins. Nevertheless, their high surface energy leads to nonspecific adsorption and poor colloidal stability. In the past decades, we have found that QD-based fluorescent nanoparticles (FNs) can not only address these limitations but also enhance detection sensitivity. However, the photoluminescence quantum yield (PLQY) of FNs is significantly lower compared with that of original QDs. It is urgent to develop a strategy to solve the issue, aiming to further enhance detection sensitivity. In this study, we found that the decrease of PLQY of FNs prepared by free radical polymerization was attributed to two factors: (1) generation of defects that can cause nonradiative transitions resulting from QD-ligands desorption and QD-shell oxidation induced by free radicals; (2) self-absorption resulting from aggregation caused by incompatibility of QDs with polymers. Based on these, we proposed a multihierarchical regulation strategy that includes: (1) regulating QD-ligands; (2) precisely controlling free radical concentration; and (3) constructing cross-linked structures of polymer to improve compatibility and to reduce the formation of surface defects. It is crucial to emphasize that the simultaneous coordination of multiple factors is essential. Consequently, a world-record PLQY of 97.6% for FNs was achieved, breaking through the current bottleneck at 65%. The flexible application of this regulatory concept paves the way for the large-scale production of high-brightness QD-polymer complexes, enhancing their potential applications in sensitive biomedical detection.

Background: High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury., Objective: To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects., Methods: 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis., Results: Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels., Conclusion: This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To explore the value of radiomics for predicting the expression of programmed death ligand 1 (PD-L1) in non-small-cell lung cancer (NSCLC) based on multiparameter spectral computed tomography (CT) images., Materials and Methods: A total of 220 patients with NSCLC were enrolled retrospectively and divided into the training (n=176) and testing (n=44) cohorts. The radiomics features were extracted from the conventional CT images, mono-energy 40 keV images, iodine density (ID) maps, Z-effective maps, and electron density maps. The logistic regression (LR) and support vector machine (SVM) algorithms were employed to build models based on radiomics signatures. The prediction abilities were qualified by the area under the curve (AUC) obtained from the receiver operating characteristic (ROC) curve. Internal validation was performed on the independent testing dataset., Results: The combined model for PD-L1 ≥1%, which consisted of the radiomics score (rad-score; p<0.0001), white blood cell (WBC; p=0.027) counts, and air bronchogram (p=0.003), reached the highest performance with the AUCs of 0.873 and 0.917 in the training and testing dataset, respectively, which was better than the radiomics model with the AUCs of 0.842 and 0.886. The combined model for PD-L1 ≥50%, which consisted of rad-score (p<0.0001) and WBC counts (p=0.027), achieved the highest performance in the training and testing dataset with AUCs of 0.932 and 0.903, respectively, which was better than the radiomics model with AUCs of 0.920 and 0.892, respectively., Conclusion: The radiomics model based on the multiparameter images of spectral CT can predict the expression level of PD-L1 in NSCLC. The combined model can obtain higher prediction efficiency and serves as a promising method for immunotherapy selection., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

The precise roles of chromatin organization at osteoporosis risk loci remain largely elusive. Here, we combined chromatin interaction conformation (Hi-C) profiling and self-transcribing active regulatory region sequencing (STARR-seq) to qualify enhancer activities of prioritized osteoporosis-associated single-nucleotide polymorphisms (SNPs). We identified 319 SNPs with biased allelic enhancer activity effect (baaSNPs) that linked to hundreds of candidate target genes through chromatin interactions across 146 loci. Functional characterizations revealed active epigenetic enrichment for baaSNPs and prevailing osteoporosis-relevant regulatory roles for their chromatin interaction genes. Further motif enrichment and network mapping prioritized several putative, key transcription factors (TFs) controlling osteoporosis binding to baaSNPs. Specifically, we selected one top-ranked TF and deciphered that an intronic baaSNP (rs11202530) could allele-preferentially bind to YY2 to augment PAPSS2 expression through chromatin interactions and promote osteoblast differentiation. Our results underline the roles of TF-mediated enhancer-promoter contacts for osteoporosis, which may help to better understand the intricate molecular regulatory mechanisms underlying osteoporosis risk loci., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition. We identify 4765 independent primary and 616 secondary cis-expression quantitative trait loci (cis-eQTLs) in the synovium and find that the eQTLs with multiple independent signals have stronger effects and heritability than single independent eQTLs. Integration of genome-wide association studies (GWASs) and eQTLs identifies 84 arthritis related genes, revealing 38 novel genes which have not been reported by previous studies using eQTL data from the GTEx project or immune cells. We further develop a method called eQTac to identify variants that could affect gene expression by affecting chromatin accessibility and identify 1517 regions with potential regulatory function of chromatin accessibility. Altogether, our study provides a comprehensive synovium multi-omics resource for arthritic diseases and gains new insights into the regulation of gene expression., (© 2024. The Author(s).)

Objective: To evaluate the efficacy and safety of multi-drug therapy based on eszopiclone in the treatment of insomnia after stroke using a network meta-analysis method and to provide evidence for clinical practice., Method: Computer searches of PubMed, Excerpt Medica Database (Embase), Cochrane Library Central Register of Controlled Trials, APA PsycInfo, CNKI, WanFang, Sinomed and other databases were performed to search for clinical randomized controlled studies (RCTs) on multi-drug therapy based on eszopiclone in the treatment of insomnia patients after stroke. The search time was from the establishment of each database until July 2023. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included RCTs. Stata 14.0 was applied to perform network meta-analysis using Review Manager 5.3 software for traditional meta-analysis., Result: Eighteen RCTs and 1646 patients were ultimately included, involving 11 treatment options. The results of the network meta-analysis showed that the ranking of Pittsburgh Sleep Quality Index (PSQI) decline was eszopiclone combined with sweet dream oral liquid (ESZ+SDOL)>eszopiclone combined with a shugan jieyu capsule (ESZ+SGJYC)>eszopiclone combined with agomelatine (ESZ+AGO)>eszopiclone combined with flupentixol and melitracen tablets (ESZ+FMT)>eszopiclone combined with yangxue qingnao granules (ESZ+YXQNG)>eszopiclone combined with mirtazapine (ESZ+MIR)>ESZ>FMT; the modified Edinburgh Scandinavia Stroke Scale (MESSS) decline ranking was ESZ+SDOL>ESZ+AGO>ESZ; and the clinical total effective rate ranking was eszopiclone combined with a xuefu zhuyu capsule (ESZ+XFZYC)>ESZ+MIR>ESZ+SGJYC>ESZ+SDOL> ESZ+FMT>ESZ+YXQNG>ESZ>FMT. In terms of clinical adverse reactions, in addition to ESZ therapy, ESZ+ESC had the highest number of adverse reactions, with abdominal pain being the most common. ESZ+YXQNG had the most types of adverse reactions, with 8 types., Conclusion: Multi-drug therapy based on eszopiclone can effectively improve the sleep quality of patients with insomnia after stroke, and ESZ+SDOL has significant efficacy and safety. However, due to the limitations of this study, efficacy ranking cannot fully explain the superiority or inferiority of clinical efficacy. In the future, more multicentre, large sample, double-blind randomized controlled trials are needed to supplement and demonstrate the results of this study., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: In this study, the color ultrasound indicators of carotid atherosclerosis (CAS) intima-media thickness (IMT) and atherosclerotic plaque (AP) were retrospectively analyzed for the prediction of CHD with the help of compressed speckle denoising., Patients and Methods: A total of 248 patients with suspected coronary atherosclerosis admitted to the Department of Cardiovascular Medicine of The First Affiliated Hospital of Harbin Medical University from August 2020 to January 2022 were retrospectively recruited as research subjects., Results: The plaque detection rate (71.83%), IMT (1.26 ± 0.75) mm, and plaque index (PI) (2.31 ± 0.95) in the Obs group were greatly higher. The IMT and PI values in the patients with two CALs were superior to those in patients with a single CAL, and the IMT and PI values in the patients with three CALs were higher than those in patients with two CALs, illustrating considerable differences between the two groups (p < 0.05). The predictive sensitivity of IMT combined with AP was higher than that of IMT and AP (p < 0.05), and the predictive specificity of AP results was markedly inferior to that of IMT and IMT combined with AP (p < 0.05)., Conclusions: The ultrasound examination of CAS had obvious predictive value for the occurrence and disease severity of CHD. The higher the IMT and AP, the higher the incidence and severity of CAD.

Introduction: Traumatic brain injury (TBI) seriously affects the quality of human health and the prognosis of the patient, but the epidemiological characteristics of TBI can vary among populations. Numerous changes have occurred in the epidemiological characteristics of individuals with TBI in the fast-paced city of Shenzhen, China. However, little is known about these characteristics. This study aimed to investigate the changes in TBI epidemiology, help clinicians improve medical treatment., Methods: In this retrospective cross-sectional analysis, we collected the data of 4,229 patients with TBI admitted to 20 hospitals in Shenzhen in 2017. We collected data on age, gender, cause and severity of the injury, eventual diagnosis, time from injury to admission in a neurosurgery department, and patient outcomes. Two neurosurgeons simultaneously collected the data. We compared these results with a similar study conducted in Shenzhen during the period from 1994 to 2003 to clarify and explain the changes in the epidemiological characteristics of TBI., Results: The majority of respondents were men [2,830 (66.9%)]. The mean age was 32.5 ± 21.4 years. The youngest patient was less than 1 year old, and the oldest patient was 101 years old. A total of 3,947 (93.3%) patients had a favorable outcome, 219 (5.2%) had an unfavorable outcome, and 63 (1.5%) died. The predominant external cause was falls (1,779 [42.1%]); this was the most common cause of TBI in children and older adults. Riders of electric bicycles (423 [29.0%]) were the most vulnerable to traffic accident-related injuries. Time greater than 50 h from injury to admission to a neurosurgical department had a significant effect on prognosis ( p  < 0.001)., Conclusion: The epidemiological characteristics of TBI have changed significantly over the past 20 years. Falls, rather than traffic accidents, were the most common cause of TBI. Further research is needed to devise solutions to decrease the incidence of falls and improve the outcomes of TBI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zou, Fang, Zheng, Ma, Wu, Su, Liu, Liu, Gao, Zhang, Zhu, Shi and Huang.)

Most of the single-nucleotide polymorphisms (SNPs) associated with insulin resistance (IR)-relevant phenotypes by genome-wide association studies (GWASs) are located in noncoding regions, complicating their functional interpretation. Here, we utilized an adapted STARR-seq to evaluate the regulatory activities of 5,987 noncoding SNPs associated with IR-relevant phenotypes. We identified 876 SNPs with biased allelic enhancer activity effects (baaSNPs) across 133 loci in three IR-relevant cell lines (HepG2, preadipocyte, and A673), which showed pervasive cell specificity and significant enrichment for cell-specific open chromatin regions or enhancer-indicative markers (H3K4me1, H3K27ac). Further functional characterization suggested several transcription factors (TFs) with preferential allelic binding to baaSNPs. We also incorporated multi-omics data to prioritize 102 candidate regulatory target genes for baaSNPs and revealed prevalent long-range regulatory effects and cell-specific IR-relevant biological functional enrichment on them. Specifically, we experimentally verified the distal regulatory mechanism at IRS1 locus, in which rs952227-A reinforces IRS1 expression by long-range chromatin interaction and preferential binding to the transcription factor HOXC6 to augment the enhancer activity. Finally, based on our STARR-seq screening data, we predicted the enhancer activity of 227,343 noncoding SNPs associated with IR-relevant phenotypes (fasting insulin adjusted for BMI, HDL cholesterol, and triglycerides) from the largest available GWAS summary statistics. We further provided an open resource (http://www.bigc.online/fnSNP-IR) for better understanding genetic regulatory mechanisms of IR-relevant phenotypes., Competing Interests: Declaration of interests The authors have declared that no conflict of interest exists., (Copyright © 2023 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Aims/introduction: The triglyceride-glucose (TyG) index is a simple and reliable indicator of insulin resistance, and is associated with the development and poor outcomes of cardiovascular disease. Subclinical left ventricular dysfunction (SLVD) is frequently detected in approximately one-third of diabetes patients, but it has not been established whether the TyG index correlates with SLVD. We carried out this research to evaluate the relationship between the TyG index and SLVD in type 2 diabetes mellitus patients., Materials and Methods: This was a cross-sectional and observational study of 183 type 2 diabetes mellitus inpatients at Nanjing Drum Tower Hospital, Nanjing, China. The TyG index and homeostasis model assessment 2 estimates for insulin resistance (HOMA2-IR) were calculated from biochemical measurements, and speckle-tracking echocardiography was carried out. According to global longitudinal strain (GLS) by echocardiography, participants were categorized into the SLVD (GLS <18%) group or the non-SLVD (GLS ≥18%) group., Results: In comparison with non-SLVD participants, SLVD participants had higher insulin resistance, as reflected by elevated TyG and HOMA2-IR indices, as well as a higher body mass index, waist circumference and triglyceride level (P < 0.05 for each). When grouped by TyG index tertiles, an elevated TyG index was correlated with other cardiometabolic risk factors, as well as a decrease in GLS. In the multivariate logistic regression analyses, the TyG index was an independent risk factor for SLVD in type 2 diabetes mellitus patients (odds ratio 2.047, 95% confidence interval 1.07-3.914, P  = 0.03), whereas HOMA2-IR was not., Conclusions: The TyG index is independently associated with SLVD in type 2 diabetes mellitus patients and is a more reliable indicator of SLVD than HOMA2-IR., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

With the rapid development of synthetic biology, various whole-cell biosensors have been designed as valuable biological devices for the selective and sensitive detection of toxic heavy metals in environmental water. However, most proposed biosensors are based on fluorescent and bioluminescent signals invisible to the naked eye. The development of visible pigment-based biosensors can address this issue. The pbr operon from Klebsiella pneumoniae is selectively induced by bioavailable Pb(II). In the present study, the proviolacein biosynthetic gene cluster was transcriptionally fused to the pbr Pb(II) responsive element and introduced into Escherichia coli . The resultant biosensor responded to Pb(II) in a time- and dose-dependent manner. After a 5-h incubation with Pb(II), the brown pigment was produced, which could be extracted into n-butanol. Extra hydrogen peroxide treatment during n-butanol extract resulted in the generation of a stable green pigment. An increased brown signal was observed upon exposure to lead concentrations above 2.93 nM, and a linear regression was fitted from 2.93 to 3,000 nM. Extra oxidation significantly decreased the difference between parallel groups. The green signal responded to as low as 0.183 nM Pb(II), and a non-linear regression was fitted in a wide concentration range from 0.183 to 3,000 nM. The specific response toward Pb(II) was not interfered with by various metals except for Cd(II) and Hg(II). The PV-based biosensor was validated in monitoring bioaccessible Pb(II) spiked into environmental water. The complex matrices did not influence the regression relationship between spiked Pb(II) and the dual-color signals. Direct reading with the naked eye and colorimetric quantification enable the PV-based biosensor to be a dual-color and low-cost bioindicator for pollutant heavy metal., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Guo, Ma, Lin, Wang, Gao, Liu, Zhang, Luo and Hui.)

Earth-abundant copper(I) coordination complexes of an imine-phosphine and a diimine have been developed as visible-light photocatalysts. Reaction of [Cu(MeCN) 4 ]BF 4 with hetero-bidentate phosphinopyrazole (phpz) ligand R 1 R 2 C 3 HN 2 PPh 3 (R 1 = R 2 = H (1a); R 1 = H, R 2 = Me (1b); R 1 = H, R 2 = Ph (1c); R 1 = R 2 = Me (1d)) and 2,9-dimethyl-1,10-phenanthroline (dmp) gave four heteroleptic bis-chelate Cu(I) complexes [Cu(dmp)(R 1 R 2 C 3 HN 2 PPh 3 )]BF 4 (R 1 = R 2 = H (2a); R 1 = H, R 2 = Me (2b); R 1 = H, R 2 = Ph (2c); R 1 = R 2 = Me (2d)) with distorted tetrahedral geometries. Complexes 2a-2d exhibited broad absorption in the visible spectrum and could facilitate photochemical intermolecular atom-transfer radical addition reactions of CBr 4 , or CCl 3 Br, CHI 3 to styrenes in yields up to 91% and with a broad substrate scope. The absorption, emission, redox potential and photocatalytic activity were dependent on the substituents on the phpz ligand. Mechanistic studies supported an atom-transfer radical addition (ATRA) mechanism.

3D genomics aims to investigate the spatial structure of chromatin in the nucleus on the basis of genomic sequences, gene structures and relevant regulatory elements. The spatial organization of chromosomes is fundamental for gene expression regulation. Recent advances of high-throughput chromosome conformation capture (Hi-C) technology and its derivatives, has enabled capture of chromatin architecture with high resolution. In this review, we summarize the development and applications of various technologies of 3D genomes in disease research, particularly in the elucidation of pathogenic mechanisms in cancers and other systemic disorders.

Genome-wide association studies (GWASs) have repeatedly reported multiple non-coding single-nucleotide polymorphisms (SNPs) at 2p14 associated with rheumatoid arthritis (RA), but their functional roles in the pathological mechanisms of RA remain to be explored. In this study, we integrated a series of bioinformatics and functional experiments and identified three intronic RA SNPs (rs1876518, rs268131, and rs2576923) within active enhancers that can regulate the expression of SPRED2 directly. At the same time, SPRED2 and ACTR2 influence each other as a positive feedback signal amplifier to strengthen the protective role in RA by inhibiting the migration and invasion of rheumatoid fibroblast-like synoviocytes (FLSs). In particular, the transcription factor CEBPB preferentially binds to the rs1876518-T allele to increase the expression of SPRED2 in FLSs. Our findings decipher the molecular mechanisms behind the GWAS signals at 2p14 for RA and emphasize SPRED2 as a potential candidate gene for RA, providing a potential target and direction for precise treatment of RA., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Although equity is an important aspect of sustainable development, equity research has mainly focused on income and economics while paying insufficient attention to ecological equity. Therefore, aiming to improve our understanding of equity and promote environmental protection, this study introduced natural capital to measure regional ecological equity and analyze its driving factors. Based on ecological footprint (EF) and ecosystem service value (ESV), we constructed evaluation indexes and drew an "ecological Lorentz curve bundle" to analyze ecological equity in the Jing-Jin-Ji urban agglomeration (JUA) from 2009 to 2020. The results showed that economic development in JUA resulted in the severe depletion of natural capital, especially biological and energy resources, and the supply and demand of natural capital was in a low-level equilibrium state. Based on JUA's population base, natural capital utilization in the region had exceeded ecological equity, and the Gini coefficient of EF based on population was close to the international warning value of 0.4. Although economic development in JUA has promoted economic equity, it has also led to environmental inequity. Large cities such as Beijing and Tianjin, as well as industrial cities such as Tangshan and Handan, have had the greatest effects on ecological equity. Moreover, the excessive consumption of natural capital stock and energy-dependent industrial structures threaten ecological equity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: Glucocorticoids have potent effects on the central nervous system. However, while patients with Cushing syndrome frequently report impairments in cognitive function, studies investigating cognitive function in patients with autonomous cortisol secretion (ACS) in adrenal incidentalomas (AIs) are scarce., Objective: The aim of the present study was to evaluate neurocognitive function in patients with ACS., Methods: We prospectively recruited 63 patients with AI, 36 patients with nonfunctional adrenal adenoma (NFA) (46.5 ± 10.5 years), and 27 patients with ACS (48.6 ± 9.1 years); these patients underwent a battery of validated neuropsychological tests. ACS was diagnosed when serum cortisol levels after a 1-mg dexamethasone suppression test (cortisol1 mg DST) ≥ 50 nmol/L., Results: Patients with ACS had higher frequency of subjective memory complaints (40.7% vs 13.9%, P < 0.05) and higher proportion of mild cognitive impairment (22.2% vs 2.8%, P < 0.05) than patients with NFA. Furthermore, patients with ACS had worse performance on working memory and the visuospatial/constructional domain than patients with NFA (all P < 0.05). Serum cortisol1 mg DST was negatively correlated with working memory and visuospatial/constructional domains (r = -0.307 and -0.306, respectively, all P < 0.05). Performance on working memory and visuospatial/constructional domains gradually deteriorated with increases in serum cortisol1 mg DST (all P values for trend < 0.05). Multivariate linear regression analysis showed that serum cortisol1 mg DST was a significant risk factor for impairment of working memory and visuospatial/constructional domains (B = -0.006 and -0.043, respectively, all P < 0.05)., Conclusion: This study is the first to report that ACS is accompanied by impaired cognitive function. Consequently, cognitive function assessment should be incorporated into the clinical evaluation of patients with ACS., Clinical Trial Registration Number: NCT05357456., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Vascular calcification, the deposition of calcium in the arterial wall, is often linked to increased stiffness of the vascular wall. Vascular calcification is one of the important factors for high morbidity and mortality of cardiovascular and cerebrovascular diseases, as well as an important biomarker in atherosclerotic cardiovascular events, stroke and peripheral vascular diseases. The mechanism of vascular calcification has not been fully elucidated. Recently, non-coding RNAs have been found to play an important role in the process of vascular calcification. In this paper, the main types of non-coding RNAs and their roles involved in vascular smooth muscle cell calcification are reviewed, including the changes of osteoblast-related proteins, calcification signaling pathways and intracellular Ca 2+ .

Objectives: To investigate the effect of inhibiting miR-204 expression on the learning and memory abilities of neonatal rats with intrauterine growth restriction (IUGR) and related mechanism., Methods: A rat model of IUGR was prepared by low-protein diet. The 3-day-old IUGR rats were divided into three groups: model, miRNA antagonist control and miR-204 antagonist, with 10 rats in each group. Ten normal neonatal rats served as the control group. Morris water maze test was used to measure the learning and memory abilities of the rats. Quantitative real-time PCR was used to measure the mRNA expression levels of miR-204 and brain-derived neurotrophic factor (BDNF) in the hippocampus. Nissl staining and TUNEL staining were used to observe the number of Nissl bodies and the apoptosis of cells in the hippocampus. Western blot was used to measure the expression levels of BDNF/TrkB signaling pathway-related proteins in the hippocampus., Results: Compared with the control group, the model group had a significant increase in the escape latency and a significant reduction in the number of platform crossings ( P <0.001). The model group also had significant increases in the apoptosis rate of cells and the expression level of miR-204 in hippocampal tissue ( P <0.001), while the number of Nissl bodies, the mRNA expression level of BDNF, and the protein expression levels of BDNF, p-TrkB, and p-CREB in the model group were significantly reduced compared with the control group ( P <0.001). After inhibition of the expression of miR-204, the number of Nissl bodies, the mRNA expression level of BDNF, and the protein expression levels of BDNF, p-TrkB, and p-CREB significantly increased, while the cell apoptosis rate and the expression level of miR-204 in the hippocampus significantly decreased. The escape latency was also reduced, while the number of platform crossings increased after inhibition of the expression of miR-204 ( P <0.001)., Conclusions: Inhibiting miR-204 can improve the learning and memory functions of neonatal rats with IUGR, possibly by targeted activation of the BDNF/TrkB signaling pathway.

Human mesenchymal stem cells (hMSCs) can be differentiated into adipocytes and osteoblasts. The processes are driven by the rewiring of chromatin architectures and transcriptomic/epigenomic changes. Here, we induced hMSCs to adipogenic and osteogenic differentiation, and performed 2 kb resolution Hi-C experiments for chromatin loops detection. We also generated matched RNA-seq, ChIP-seq and ATAC-seq data for integrative analysis. After comprehensively comparing adipogenesis and osteogenesis, we quantitatively identified lineage-specific loops and screened out lineage-specific enhancers and open chromatin. We reveal that lineage-specific loops can activate gene expression and facilitate cell commitment through combining enhancers and accessible chromatin in a lineage-specific manner. We finally proposed loop-mediated regulatory networks and identified the controlling factors for adipocytes and osteoblasts determination. Functional experiments validated the lineage-specific regulation networks towards IRS2 and RUNX2 that are associated with adipogenesis and osteogenesis, respectively. These results are expected to help better understand the chromatin conformation determinants of hMSCs fate commitment., (© 2022. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Metabolic engineered bacteria have been successfully employed to produce various natural colorants, which are expected to be used as the visually recognizable signals to develop mini-equipment biological devices for monitoring toxic heavy metals. The violacein biosynthetic pathway has been reconstructed in Escherichia coli (E. coli). Here the successful production of four violacein derivatives was achieved by integrating metabolic engineering and synthetic biology. Lead binding to the metalloregulator enables whole-cell colorimetric biosensors capable of assessing bioavailable lead. Deoxyviolacein-derived signal showed the most satisfied biosensing properties among prodeoxyviolacein (green), proviolacein (blue), deoxyviolacein (purple), and violacein (navy). The limit of detection (LOD) of pigment-based biosensors was 2.93 nM Pb(II), which is lower than that of graphite furnace atomic absorption spectrometry. Importantly, a good linear dose-response model in a wide dose range (2.93-6000 nM) was obtained in a non-cytotoxic deoxyviolacein-based biosensor, which was significantly better than cytotoxic violacein-based biosensor (2.93-750 nM). Among ten metal ions, only Cd(II) and Hg(II) exerted a slight influence on the response of the deoxyviolacein-based biosensor toward Pb(II). The deoxyviolacein-based biosensor was validated in detecting bioaccessible Pb(II) in environmental samples. Factors such as low cost and minimal-equipment requirement make this biosensor a suitable biological device for monitoring toxic lead in the environment., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Environmental lead pollution mainly caused by previous anthropogenic activities continuously threatens human health. The determination of bioavailable lead is of great significance to predict its ecological risk. Bacterial biosensors using visual pigments as output signals have been demonstrated to have great potential in developing minimal-equipment biosensors for environmental pollutant detection. In this study, the biosynthesis pathway of anthocyanin was heterogeneously reconstructed under the control of the PbrR-based Pb(II) sensory element in Escherichia coli . The resultant metabolic engineered biosensor with colored anthocyanin derivatives as the visual signal selectively responded to concentrations as low as 0.012 μM Pb(II), which is lower than the detection limit of traditional fluorescent protein-based biosensors. A good linear dose-response pattern in a wide Pb(II) concentration range (0.012-3.125 μM) was observed. The color deepening of culture was recognized to the naked eye in Pb(II) concentrations ranging from 0 to 200 μM. Importantly, the response of metabolic engineered biosensors toward Pb(II) was not significantly interfered with by organic and inorganic ingredients in environmental water samples. Our findings show that the metabolic engineering of natural colorants has great potential in developing visual, sensitive, and low-cost bacterial biosensors for the detection and determination of pollutant heavy metals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Huang, Zhu, Hu, Li and Hui.)

Osteoporosis is an age-related complex disease clinically diagnosed with bone mineral density (BMD). Although several genomewide association studies (GWASs) have discovered multiple noncoding genetic variants at 11p15 influencing osteoporosis risk, the functional mechanisms of these variants remain unknown. Through integrating bioinformatics and functional experiments, a potential functional single-nucleotide polymorphism (SNP; rs1440702) located in an enhancer element was identified and the A allele of rs1440702 acted as an allelic specificities enhancer to increase its distal target gene SOX6 (~600 Kb upstream) expression, which plays a key role in bone formation. We also validated this long-range regulation via conducting chromosome conformation capture (3C) assay. Furthermore, we demonstrated that SNP rs1440702 with a risk allele (rs1440702-A) could increase the activity of the enhancer element by altering the binding affinity of the transcription factor TCF4, resulting in the upregulation expression of SOX6 gene. Collectively, our integrated analyses revealed how the noncoding genetic variants (rs1440702) affect osteoporosis predisposition via long-range gene regulatory mechanisms and identified its target gene SOX6 for downstream biomarker and drug development. © 2022 American Society for Bone and Mineral Research (ASBMR)., (© 2022 American Society for Bone and Mineral Research (ASBMR).)

Context: Autonomous cortisol secretion (ACS) affects up to 30% of patients with adrenal incidentalomas (AIs). The current guidelines for ACS diagnosis are not decisive. A lower dehydroepiandrosterone sulfate (DHEAS) level is a potential biomarker, but the evidence is conflicting., Objective: This prospective study aimed to evaluate and validate the ACS screening and diagnostic accuracy of DHEAS., Methods and Patients: Recruited patients with AI were screened for adrenal medullary and cortisol hypersecretion. The diagnosis of ACS was based on a serum cortisol level ≥ 50 nmol/L following a 1-mg dexamethasone suppression test (DST) and a low-dose DST. Age- and sex-specific DHEAS ratios were also calculated., Results: In the development cohort (45 ACS and 242 non-ACS patients), the areas under the receiver operator characteristic curves (AUCs) of DHEAS and the DHEAS ratio were 0.869 (95% CI 0.824-0.906) and 0.799 (95% CI 0.748-0.844), respectively. The optimal DHEAS cutoff for diagnosing ACS was 60 μg/dL, with a sensitivity of 75.6% (95% CI 60.5-87.1) and a specificity of 81.4% (95% CI 76.4-86.5). The midnight serum cortisol level had moderate diagnostic accuracy [AUC 0.875 (95% CI 0.831-0.911)]. Suppressed adrenocorticotropic hormone (≤2.2 pmol/L) had a lower sensitivity (55.6%), and the 24-hour urinary free cortisol lacked sensitivity and specificity [AUC 0.633 (95% CI 0.603-0.721)]. In the validation cohort (14 ACS and 45 non-ACS patients), the sensitivity and specificity of the optimized DHEAS cutoff were 71.4% (95% CI 41.9-91.6) and 82.2% (95% CI 68.0-92.0), respectively., Conclusions: A single basal measurement of DHEAS is valuable for identifying ACS. Because of its stability and ease of use, the DHEAS level could be used as an ACS screening test., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We have developed a catalyst-free visible-light-driven C(sp 2 )-H arylation of unprotected phenols with arylbromides to give 2-arylated phenols. This reaction proceeds through the excitation of an electron donor-acceptor complex between a phenolate and an arylbromide, electron transfer, and debrominative C(sp 2 )-C(sp 2 ) coupling.

Chronic subdural hematoma (CSDH) is a common neurological disease that involves the collection of blood products in the subdural space. The progression of CSDH is an angiogenic and inflammatory process, but the multifactorial mechanisms underlying CSDH are still not fully understood. We aimed to identify one or more factors that may play an important role in the development of CSDH. We enrolled 83 patients with CSDH, including 17 postoperative patients, and analyzed 20 markers in the hematoma fluid and peripheral blood of each patient. Overall differential gene expression was examined to identify the representative markers. The concentration of MMP-8 was significantly lower in the postoperative group than in the preoperative group. The concentration of MMP-9 was significantly higher in the postoperative group than in the preoperative group. These findings indicate that MMP-8 and MMP-9 may play important roles in the pathophysiology of CSDH. Understanding the pathways associated with CSDH may provide insights for improving disease outcomes.

Rationale: Hydrocephalus is a common disease in neurosurgery. The typical symptoms of hydrocephalus include urinary incontinence, gait instability, and cognitive decline. Irritability rarely occurs in patients with hydrocephalus. Irritability rarely occurs in patients with hydrocephalus, especially in long-standing overt ventriculomegaly of adulthood (LOVA)., Patient Concerns: A 30-year-old female was admitted to our hospital because of mental retardation and unstable gait for more than 15 years. She had undergone ventriculoperitoneal shunt 15 years prior due to ventriculomegaly and related symptoms. However, the shunt catheter was removed shortly after surgery because of blockage, with no further postoperative treatment., Diagnosis: The patient was diagnosed with long-standing overt ventriculomegaly according to her head circumference and clinical symptoms, including adult hydrocephalus development, overt triventriculomegaly and absence of a secondary cause for aqueductal stenosis in adulthood., Interventions: After considerable discussion, she underwent ventriculoperitoneal shunt placement and showed dramatic and sustained improvement., Outcomes: The patient has been followed at 3-month intervals for over 2 years since discharge, and both the patient and family have reported a significant change in their daily life. She was able to live independently and control her emotions. Slight epilepsy was noted approximately 5 months after surgery but recovered 2 months later., Lessons: It is difficult to decide whether to treat LOVA when the in patients whose symptoms are not significant. We believe that early diagnosis and positive treatment can help improve outcomes and would recommend ventriculoperitoneal (VP) shunting in patients with LOVA., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Notwithstanding some progress in nickel-catalyzed etherification of alkanols and arylhalides, the ability of such a Ni-catalyzed transformation employing phenols to diaryl ethers is unsuccessful due to phenolates with much lower reduction potentials, which suppress the oxidation of nickel(II) intermediates into requisite Ni(III) species. We herein report visible-light-initiated, nickel-catalyzed O-arylation of phenols with arylhalides using t -BuNH( i -Pr) as the base and thioxanthen-9-one as the photosensitizer under visible light. This photocoupling exhibits a broad substrate scope.

Pulmonary arterial hypertension (PAH) is a rare disease with a complex aetiology characterized by elevated pulmonary artery resistance, which leads to progressive right ventricular failure and ultimately death. The aberrant metabolism of arachidonic acid in the pulmonary vasculature plays a central role in the pathogenesis of PAH. The levels of 15-lipoxygenase (15-LO) and 15-hydroxyeicosatetraenoic acid (15-HETE) are elevated in the pulmonary arterial endothelial cells (PAECs), pulmonary smooth muscle cells (PASMCs) and fibroblasts of PAH patients. Under hypoxia condition, 15-LO/15-HETE induces pulmonary artery contraction, promotes the proliferation of PAECs and PASMCs, inhibits apoptosis of PASMCs, promotes fibrosis of pulmonary vessels, and then leads to the occurrence of PAH. Here, we review the research progress on the relationship between 15-LO/15-HETE and hypoxic PAH, in order to clarify the significance of 15-LO/15-HETE in hypoxic PAH.

Genome-wide association studies (GWAS) have reproducibly associated the single nucleotide polymorphism (SNP) rs12454712 with waist-to-hip ratio adjusted for BMI (WHRadjBMI), but the functional role underlying this intronic variant is unknown. Integrative genomic and epigenomic analyses supported rs12454712 as a functional independent variant. We further demonstrated that rs12454712 acted as an allele-specific enhancer regulating expression of its located gene BCL2 by using dual-luciferase reporter assays and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9. Specifically, the rs12454712-C allele can bind transcription factor ZNF329, which efficiently elevates the enhancer activity and increases BCL2 expression. Knocking down Bcl2 in 3T3-L1 cells led to the downregulation of adipogenic differentiation marker genes and increased cell apoptosis. A significant negative correlation between BCL2 expression in subcutaneous adipose tissues and obesity was observed. Our findings illustrate the molecular mechanisms behind the intronic SNP rs12454712 for central obesity, which would be a potential and promising target for developing appropriate therapies., (© 2021 by the American Diabetes Association.)

Detecting SNPs associated with drug efficacy or toxicity is helpful to facilitate personalized medicine. Previous studies usually find SNPs associated with clinical outcome only in patients received a specific treatment. However, without information from patients without drug treatment, it is possible that the detected SNPs are associated with patients' clinical outcome even without drug treatment. Here we aimed to detect drug response SNPs based on data from patients with and without drug treatment through combing the cox proportional-hazards model and pairwise Kaplan-Meier survival analysis. A pipeline named Detection of Drug Response SNPs (DDRS) was built and applied to TCGA breast cancer data including 363 patients with doxorubicin treatment and 321 patients without any drug treatment. We identified 548 doxorubicin associated SNPs. Drug response score derived from these SNPs were associated with drug-resistant level (indicated by IC 50 ) of breast cancer cell lines. Enrichment analyses showed that these SNPs were enriched in active epigenetic regulation markers (e.g., H3K27ac). Compared with random genes, the cis -eQTL genes of these SNPs had a shorter protein-protein interaction distance to doxorubicin associated genes. In addition, linear discriminant analysis showed that the eQTL gene expression levels could be used to predict clinical outcome for patients with doxorubicin treatment (AUC = 0.738). Specifically, we identified rs2817101 as a drug response SNP for doxorubicin treatment. Higher expression level of its cis -eQTL gene GSTA1 is associated with poorer survival. This approach can also be applied to identify new drug associated SNPs in other cancers., 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., (© 2021 The Author(s).)

Background: The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D., Methods: This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses., Results: After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed., Conclusion: One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone., Trial Registration: ChiCTR2100045434 . Registered on April 15, 2021-retrospectively registered, http://www.chictr.org.cn/.

Introduction: The aim of this study was to clarify the efficacy and safety of metabolic surgery in Chinese patients with type 2 diabetes mellitus (T2DM) and a body mass index (BMI) of 27.5-32.5 kg/m 2 ., Methods: A total of 99 patients with T2DM were enrolled in this retrospective cohort study. Of these patients, 53 had a BMI of 27.5-32.5 kg/m 2 and had undergone metabolic surgery (n = 21) or were on conventional antidiabetic therapy (n = 32)]; 46 had a BMI ≥ 32.5 kg/m 2 and all had undergone metabolic surgery. Primary endpoints included the triple endpoint [hemoglobin A1c < 6.5%, low-density lipoprotein cholesterol (LDL-C) < 2.6 mmol/L, and systolic blood pressure (SBP) < 130 mmHg] and successful weight loss 1 year later. Remission of diabetes, glucose and lipid metabolism, medication usage, and adverse events were evaluated., Results: Of patients with BMI 27.5-32.5 kg/m 2 undergoing metabolic surgery, 33.33% achieved the composite endpoints, and 100% achieved successful weight loss. This result was similar to that in patients with BMI ≥ 32.5 and better than those with BMI 27.5-32.5 kg/m 2 receiving conventional antidiabetic therapy. A significant and similar reduction in BMI, waist circumference, SBP, serum LDL-C, hemoglobin A1c, and uric acid, as well as similar frequency postoperative adverse events, were confirmed in both metabolic surgery groups. Patients with BMI 27.5-32.5 kg/m 2 who had undergonemetabolic surgery showed more metabolic improvement than those only receiving medications but they experienced more adverse events., Conclusion: A BMI cutoff of 27.5 kg/m 2 for metabolic surgery may be suitable for Chinese patients with T2DM.

We studied the effects of birinapant, a mimetic of the second mitochondria-derived activator of caspase (SMAC), on invasion and proliferation of MGC-803 gastric cancer cells and the molecular mechanisms underlying these processes. The expression of cellular inhibitor of apoptosis 1 (cIAP1) and TNF receptor-associated factor 3 (TRAF3) in gastric cancer cell line MGC-803 and normal gastric mucosa GES-1 cells were analyzed by Western blotting and cell immunofluorescence assay. After pretreatment of MGC-803 cells with birinapant, a Transwell invasion assay was used to evaluate the cell invasion ability. MGC-803 cells were implanted under the skin of BALB/c nude mice. The tumors were removed 10 days later and its size was measured. Protein expression of proliferating cell nuclear antigen (PCNA) in the subcutaneous tumors was analyzed by immunohistochemical method. In addition, the expression of cIAP1, TRAF3, pNF-κB, and NF-κB in control and birinapant-treated cells was compared by Western blotting and the rate of cell apoptosis was evaluated by flow cytometry. In untreated MGC-803 gastric cancer cells, the expression of cIAP1 was higher and the expression of TRAF3 was lower than in normal gastric mucosa cell line GES-1. Pretreatment with birinapant inhibited the invasion and proliferation of MGC-803 cells and promoted cell apoptosis. Birinapant also promoted the expression of TRAF3 and inhibited the expression of cIAP1 and pNF-κB in MGC-803 cells. Thus, birinapant inhibited the expression of cIAP1, prevented degradation of TRAF3, and suppressed invasion and proliferation of MGC-803 cells by promoting cell apoptosis.

Aims: Accumulating evidence indicates that serum- and glucocorticoid-inducible kinase 1 (SGK1) plays a role in the development of metabolic syndrome via a poorly understood mechanism. This study aimed to investigate the direct effect of SGK1 on insulin sensitivity in adipose tissue., Materials and Methods: We ectopically expressed or silenced SGK1 in adipocytes via lentiviral transfection, measured glucose uptake and evaluated insulin signalling using western blotting. In vivo insulin resistance was measured at the whole-body and adipose tissue levels in db/db mice treated with an inhibitor of SGK1., Results: After 8 weeks of SGK1 inhibitor treatment, the serum insulin level and homeostasis model assessment of insulin resistance index were significantly decreased, and AKT phosphorylation in adipose tissue was enhanced in db/db mice. Overexpression of constitutively active SGK1 in adipocytes in vitro decreased AKT phosphorylation and insulin-stimulated glucose uptake. Dexamethasone and oleic acid increased SGK1 expression and decreased AKT phosphorylation and insulin receptor substrate expression in adipocytes. Administration of an inhibitor of SGK1 or Lv-shSGK1 reversed the suppression of insulin signalling induced by dexamethasone and oleic acid. SGK1 overexpression increased FoxO1 phosphorylation, and administration of Lv-shSGK1 reversed an increase in FoxO1 phosphorylation induced by dexamethasone and oleic acid., Conclusions: Thus, SGK1 mediates the effect of glucocorticoids and high-fat feeding and induces insulin resistance in adipocytes. Our data suggest that SGK1 is a possible therapeutic target for metabolic syndrome and related complications., (© 2021 John Wiley & Sons Ltd.)

Objective: To investigate the prevalence and associated risk factors of pre-hypertension and hypertension in young and middle-aged population in Nanjing. Methods: Subjects of the study were those who underwent physical examination in the physical examination center of Nanjing Drum Tower Hospital from 2009 to 2016. The prevalence and risk factors of pre-hypertension and hypertension in young (aged 18-44 years old) and middle-aged people (aged 45-59 years old) were analyzed. Results: A total of 142 857 participants aged 18-59 years old were analyzed. Among them, 64 220 cases in the pre-hypertension group and 13 912 cases in the hypertension group. The prevalence of hypertension was 9.74% (12.51% in males and 5.82% in females). The prevalence of pre-hypertension was 44.95% (53.31% in males and 33.15% in females). In the middle-aged group, the prevalence of pre-hypertension and hypertension were 51.68% and 15.13%, respectively, which was higher than that in the young group (37.95% and 4.13%, respectively). The prevalence of pre-hypertension and hypertension in 2013-2016 was 45.37% and 10.65%, respectively, which was higher than that in 2009-2012(44.52% and 8.78%). In addition, the prevalence of abnormal blood glucose metabolism, abnormal blood lipid metabolism and abnormal glucose and lipid metabolism in the pre-hypertension group was higher than that in the normal blood pressure group, but lower than that in the hypertension group ( P <0.001). A logistic regression analysis indicated that age, overweight or obesity, hyperglycemia, hypertriglyceridemia and hypercholesterolemia were risk factors of pre-hypertension in male. Age, overweight or obesity, hyperglycemia, hypertriglyceridemia, hypercholesterolemia and hyper-low density cholesterolemia were associated with hypertension in male and with pre-hypertension and hypertension in female. Conclusions: Middle age, overweight/obesity, elevated fasting plasma glucose, elevated triglyceride and elevated total cholesterol were risk factors of pre-hypertension and hypertension in both men and women. Intervention on the related risk factors should be conducted as early as possible.

High-performance ultraviolet (UV) detectors with both high responses and fast speeds are hard to make on homogeneous crystal semiconductor materials. Here, the UV response characteristics of mixed-phase MgZnO thin films with different internal structure distributions are studied. The mixed-phase MgZnO-based detector with the given crystal composition has a high response at both deep UV light (96 A W -1 at 240 nm) and near UV light (80 A W -1 at 335 nm). Meanwhile, because of the quasi-tunneling breakdown mechanism within the device, the high-response UV detector also shows a fast response speed (t r  = 0.11 μs) and recovery speed (t d1  = 26 μs) at deep UV light, which is much faster than both low-response mixed-phase MgZnO-based UV detectors with other structure constitutions and reported high-response UV devices on homogenous crystal materials. The I dark of the device is just 4.27 pA under a 5 V bias voltage, so the signal-to-noise ratio of the device reached 23852 at 5.5 uW cm -2 235 nm UV light. The new quasi-tunneling breakdown mechanism is observed in some mixed-phase MgZnO thin films that contain both c-MgZnO and h-MgZnO parts, which introduce a high response, signal-to-noise ratio, and fast speed into mixed-phase MgZnO-based UV detectors at weak deep UV light.