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Xiu-Jie Zhao,1 Chun-Yu Bai,2 Xiao-Yan Li,1 Lei Wang,2 Ren-Ping Wang,2 Yue Xia,1,2 Gang Liu,1 Hong-Liang Zhao,1,* Hong-Zun Xu2,* 1Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, People’s Republic of China; 2Department of Cardiology, Shijiazhuang Great Wall Cardiovascular Hospital, Shijiazhuang, 050035, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong-Liang Zhao; Hong-Zun Xu, Email Doc_zhl@163.com; 116281970@qq.comAbstract: Carvajal syndrome is a rare hereditary cardiocutaneous syndrome caused by the variants of the desmoplakin (DSP) gene. In this study, we report a patient of Carvajal syndrome with a novel homozygous missense variant of DSP gene. We diagnosed a 7-year-old female patient with Carvajal syndrome characterized by dilated cardiomyopathy, palmoplantar keratoderma, woolly hair, and dental dysplasia, who disclosed a novel homozygous missense variant c.4597C > T (p.Q1533X) in exon 6 of the DSP gene found for the first time. Both her parents were heterozygous for the identified nonsense variant c.4597C > T (p.Q1533X) in DSP gene but neither showed evidence of Carvajal syndrome, indicating that this novel variant causes the disease in an autosomal recessive manner. Genotypes of Carvajal syndrome are even broader than so far anticipated. When patients with dilated cardiomyopathy, palmoplantar keratoderma, woolly hair, and dental dysplasia are found in clinical practice, Carvajal syndrome should be highly suspected, and family gene sequencing should be actively carried out.Keywords: Carvajal syndrome, desmoplakin, genotype, variant, novel

Shu-Jie Pang,1,&ast; Zhe Sun,1,&ast; Wen-Feng Lu,1,&ast; Hui Si-Ma,1 Zhi-Peng Lin,2 Yang Shi,1 Ying-Cheng Yang,1 Xi-Jun Zhao,1 Guang-Shun Yang,1 Guang-Zhi Jin,3 Ning Yang1 1Department V of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People’s Republic of China; 2Department of Hepatobiliary Surgery, The 940th Hospital of CPLA Joint Logistics Support Force, Lanzhou, 730050, People’s Republic of China; 3Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Yang, Department V of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People’s Republic of China, Tel +86 21 81877591, Fax +86 21 6556 6851, Email lancet00@163.com Guang-Zhi Jin, Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, People’s Republic of China, Email jgzhi@hotmail.comBackground: RBM10ʹs function in hepatocellular carcinoma (HCC) has rarely been addressed. We intend to explore the prognostic significance and therapeutic meaning of RBM10 in HCC in this study.Methods: Multiple common databases were integrated to analyze the expression status and prognostic meaning of RBM10 in HCC. The relationship between RBM10 mRNA level and clinical features was also assessed. Multiple enrichment analyses of the differentially expressed genes between RBM10 high- and low- transcription groups were constructed by using R software (version 4.0.2). A Search Tool for Retrieval of Interacting Genes database was used to construct the protein–protein interaction network between RBM10 and other proteins. A tumor immune estimation resource database was employed to identify the relationship between RBM10 expression and immune cell infiltrates. The prognostic value of RBM10 expression was validated in our HCC cohort by immunohistochemistry test.Results: The transcription of RBM10 mRNA was positively correlated with tumor histologic grade (p < 0.001), T classification (p < 0.001), and tumor stage (p < 0.001). High transcription of RBM10 in HCC predicted a dismal overall survival (p = 0.0037) and recurrence-free survival (p < 0.001). Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene Set Enrichment Analysis all revealed that RBM10 was involved in the regulation of cell cycle, DNA replication, and immune-related pathways. Tumor immune estimation analysis revealed that RBM10 transcription was positively related to multiple immune cell infiltrates and the expressions of PD-1 and PD-L1.Conclusion: RBM10 was demonstrated to be a dismal prognostic factor and a potential biomarker for immune therapy in HCC in that it may be involved in the immune-related signaling pathways.Keywords: RBM10, hepatocellular carcinoma, prognosis, differentially expressed gene, integrated bioinformatics analysis

Bin Ren,1,2,&ast; Zhong-Chao Cai,1,&ast; Xue-Jie Zhao,1 Lin-Song Li,1 Mei-Xia Zhao1 1Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Jinming Campus, Kaifeng, Henan, 475004, People’s Republic of China; 2School of Mathematics and Statistics, Henan University, Jinming Campus, Kaifeng, 475004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei-Xia ZhaoKey Laboratory of Natural Medicine and Immune Engineering of Henan Province, Henan University, Jinming Campus, Kaifeng, Henan, 475004, People’s Republic of ChinaEmail zhaomeixia2011@henu.edu.cnPurpose: Gold nanoparticles (AuNPs) with good physical and biological properties are often used in medicine, diagnostics, food, and similar industries. This paper explored an AuNPs drug delivery system that had good target selectivity for folate-receptor overexpressing cells to induce apoptosis.Methods: A novel drug delivery system, Au@MPA-PEG-FA-PTX, was developed carrying paclitaxel (PTX) on folic acid (FA) and polyethylene glycol (PEG)-modified AuNPs. The nanomaterial was characterized by transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and ultraviolet-visible spectroscopy (UV-Vis). Also, the biological activity of the AuNPs drug delivery system was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HL-7702, Hela, SMMC-7721, and HCT-116 cells. Furthermore, apoptotic activity using annexin V-FITC, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels was estimated by flow cytometry and fluorescence microscopy.Results: Au@MPA-PEG-FA-PTX exhibited a distinct core-shell structure with a controllable size of 28± 1 nm. Also, the AuNPs maintained good dispersion and spherical shape uniformity before and after modification. The MTT assay revealed good antitumor activity of the Au@MPA-PEG-FA-PTX against the Hela, SMMC-7721, and HCT-116 cells, while Au@MPA-PEG-FA-PTX produced better pharmacological effects than PTX in isolation. Further mechanistic investigation revealed that effective internalization of AuNPs by folate-receptor overexpressing cancer cells induced cell apoptosis through excessive production of intracellular ROS.Conclusion: The AuNPs drug delivery system showed good target selectivity for folate-receptor overexpressing cancer cells to induce target cell-specific apoptosis. These AuNPs may have great potential as theranostic agents such as in cancer.Keywords: gold nanoparticles, folic acid, paclitaxel, drug delivery system, apoptosis

Shu Li,1 Fu-Zheng Guo,2 Xiu-Juan Zhao,1 Qi Wang,3 Hui Wang,3 You-Zhong An,1 Feng-Xue Zhu1,21Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Trauma Centre, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of ChinaPurpose: Active surveillance of carbapenem-resistant Enterobacteriaceae (CRE) may contribute to the decline of the infection rate. Individualized active surveillance of CRE could cost less than screening all patients. However, the impact of individualized active surveillance on the CRE infection rate in intensive care units (ICUs) has not been well described.Patients and methods: We retrospectively studied the clinical data of all patients admitted in the ICUs of a tertiary-care hospital in China from 2015 to 2017 during two periods, before and after the implementation of individualized active surveillance. During period 1 (January 2015–April 2016), no screening protocol was used. During period 2 (May 2016–December 2017), we implemented active CRE screening for selected patients according to their clinical characteristics. The trend of CRE rate infection was analyzed by a joinpoint regression model, and multivariate analysis was performed to analyze the association of active surveillance, Acute Physiology and Chronic Health Evaluation (APACHE) II score, prior antimicrobial use, length of mechanical ventilation (MV) before infection, and other risk factors with CRE infection rate.Results: A total of 5,372 patients were included. After assessing the patients’ clinical characteristics, 72.3% (3,882/5,372) were considered to be at high risk of CRE infection. During period 1, the infection percent of CRE increased by 13.04% every month (95% CI: 5.2–21.5). During period 2, the infection rate decreased (monthly percent change, −3.57%; 95% CI −6.9 to −0.1, P

Xinjun Zhao,1,2,* Yue Hua,1,2,* Hongmei Chen,1,2,* Haiyu Yang,3,* Tao Zhang,1,2,* Guiqiong Huang,4,* Huijie Fan,1,2 Zhangbin Tan,1,2 Xiaofang Huang,1,2 Bin Liu,5 Yingchun Zhou1,21The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangdong, Guangzhou, People’s Republic of China; 2Nanfang Hospital, Southern Medical University, Guangdong, Guangzhou, People’s Republic of China; 3Jiangmen Wuyi Traditional Chinese Medicine Hospital, Guangdong, Jiangmen, People’s Republic of China; 4Huizhou Hospital of Traditional Chinese Medicine, Huizhou, People’s Republic of China; 5The Second Affiliated Hospital of Guangzhou Medical University, Guangdong, Guangzhou, People’s Republic of China*These authors contributed equally to this workBackground: Aldehyde dehydrogenase-2 (ALDH2) has a protective effect on ischemic heart disease. Here, we examined the protective effects of ALDH2 on cardiac fibrosis through modulation of the Wnt/ß-catenin signaling pathway in a rat model of myocardial infarction (MI).Methods: Wistar rats were divided into the sham (control), MI (model), and ALDH2 activator (Alda-1) groups. After 10 days of treatment, the left ventricular (LV) remodeling parameters of each animal were evaluated by echocardiography. Myocardial fibrosis was evaluated by Masson’s trichrome staining and Sirius Red staining. Expression levels of collagen types I and III and β-smooth muscle actin (α-SMA) were examined. Finally, the expression and activity of ALDH2 and the levels of several Wnt-related proteins and genes, such as phospho-glycogen synthase kinase (GSK)-3β, GSK-3β, β-catenin, Wnt-1, WNT1-inducible signaling-pathway protein 1, and tumor necrosis factor (TNF)-α, were also analyzed.Results: After MI, the heart weight/body weight ratio, LV dimension at end diastole, and LV dimension at end systole were decreased, while the LV ejection fraction and LV fractional shortening were increased in the Alda-1 group. Myocardial fibrosis was also reduced in the Alda-1 group, accompanied by decreased expression collagen types I and III and α-SMA. β-Catenin, phosphorylated GSK-3β, and Wnt-1 levels were significantly increased in the model group. Interestingly, this alteration was partly reversed by Alda-1 treatment. Immunohistochemical staining showed that numerous WNT1-inducible signaling-pathway protein 1 (WISP-1)- and TNF-α-positive cells were found in the model group. However, few WISP-1- and TNF-α-positive cells were detected in the Alda-1 group.Conclusion: The reduction of cardiac fibrosis and the down-regulation of β-catenin, phosphorylated GSK-3β, Wnt-1, and WISP-1 may be mediated by increased ALDH2 activity, leading to reduction of MI-related cardiac fibrosis.Keywords: myocardial infarction, aldehyde dehydrogenase, cardiac fibrosis, Wnt signaling

Jingping Liu,1 Shuyun Liu,1 Younan Chen,1 Xiaojun Zhao,2 Yanrong Lu,1 Jingqiu Cheng1 1Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, 2Laboratory of Nanomedicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: Islet transplantation is considered to be a curative treatment for type 1 diabetes mellitus. However, disruption of the extracellular matrix (ECM) leads to β-cell destruction and graft dysfunction. In this study, we developed a functionalized self-assembling peptide, KLD-F, with ECM mimic motifs derived from fibronectin and collagen IV, and evaluated its effect on β-cell function and proliferation. Atomic force microscopy and rheological results showed that KLD-F could self-assemble into a nanofibrous scaffold and change into a hydrogel in physiological saline condition. In a three-dimensional cell culture model, KLD-F improved ECM remodeling and cell-cell adhesion of INS-1 β-cells by upregulation of E-cadherin, fibronectin, and collagen IV. KLD-F also enhanced glucose-stimulated insulin secretion and expression of β-cell function genes, including Glut2, Ins1, MafA, and Pdx-1 in INS-1 cells. Moreover, KLD-F promoted proliferation of INS-1 β-cells and upregulated Ki67 expression by mediating cell cycle progression. In addition, KLD-F improved β-cell function and proliferation via an integrin/focal adhesion kinase/extracellular signal-regulated kinase/cyclin D pathway. This study highlights the fact that the β-cell-ECM interaction reestablished with this functionalized self-assembling peptide is a promising method to improve the therapeutic efficacy of islet transplantation. Keywords: extracellular matrix, self-assembling peptide, islet transplantation, β-cell proliferation, insulin secretion

Xiaojing Zhao,1,2,* Qi Chen,3,* Wei Liu,1,2 Yusang Li,3 Hebin Tang,3 Xuhan Liu,1,2 Xiangliang Yang1,2 1College of Life Science and Technology, 2National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, 3Department of Pharmacology, College of Pharmacy, South-Central University for Nationalities, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Liver cancer is a leading cause of cancer deaths worldwide. The combination therapy of cytotoxic and chemosensitizing agents loaded in nanoparticles has been highlighted as an effective treatment for different cancers. However, such studies in liver cancer remain very limited. In our study, we aim to develop a novel lipid nanoparticles loaded with doxorubicin (DOX) (an effective drug for liver cancer) and curcumin (Cur) (a chemosensitizer) simultaneously, and we examined the efficacy of chemotherapy in liver cancer. DOX and Cur codelivery lipid nanoparticles (DOX/Cur-NPs) were successfully prepared using a high-pressure microfluidics technique, showing a mean particle size of around 90 nm, a polydispersity index 90% for both DOX and Cur. The blank lipid nanoparticles were nontoxic, as determined by a cell cytotoxicity study in human normal liver cells L02 and liver cancer cells HepG2. In vitro DOX release studies revealed a sustained-release pattern until 48 hours in DOX/Cur-NPs. We found enhanced cytotoxicity and decreased inhibitory concentration (IC)50 in HepG2 cells and reduced cytotoxicity in L02 cells treated with DOX/Cur-NPs, suggesting the synergistic effects of DOX/Cur-NPs compared with free DOX and DOX nanoparticles (NPs). The optimal weight ratio of DOX and Cur was 1:1. Annexin-V-fluorescein isothiocyanate/propidium iodide double staining showed enhanced apoptosis in HepG2 cells treated with DOX/Cur-NPs compared with free DOX and DOX-NPs. An in vivo experiment showed the synergistic effect of DOX/Cur-NPs compared with DOX-NPs on liver tumor growth inhibition. Taken together, the simultaneous delivery of DOX and Cur by DOX/Cur-NPs might be a promising treatment for liver cancer. Keywords: doxorubicin, curcumin, codelivery, liver cancer, cytotoxicity, tumor growth inhibition

Dongxi Xiang,1 Yang Zheng,2 Wei Duan,1 Xiujing Li,3 Jianjian Yin,3 Sarah Shigdar,1 Michael Liam O’Connor,1 Manju Marappan,1 Xiaojuan Zhao,4 Yingqiu Miao,3 Bin Xiang,5 Conglong Zheng31School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia; 2Department of Pharmacology, Osaka University, Osaka, Japan; 3Department of Biology, Medical College, Dalian University, Liaoning, People’s Republic of China; 4Department of Gynaecology and Obstetrics, Qingdao Central Hospital, Shandong, People’s Republic of China; 5Department of Oral Medicine and Medical Research Center, Medical College, Dalian University, Liaoning, People’s Republic of ChinaAbstract: Silver nanoparticles (AgNPs) have attracted much attention as antimicrobial agents and have demonstrated efficient inhibitory activity against various viruses, including human immunodeficiency virus, hepatitis B virus, and Tacaribe virus. In this study, we investigated if AgNPs could have antiviral and preventive effects in A/Human/Hubei/3/2005 (H3N2) influenza virus infection. Madin-Darby canine kidney cells infected with AgNP-treated H3N2 influenza virus showed better viability (P

Contents Protein disulphide isomerase family A3 (PDIA3) has an activity of thioredoxin, widely expressed in multiple tissues and involved in multiple cellular processes. It was recently found in human and mouse sperm cells and could affect sperm-egg fusion. Therefore, the present investigation aims to identify PDIA3 mRNA and protein in rat testis and sperm cells. Rat PDIA3 cDNA was cloned by RT-PCR. The cRNA riboprobe was transcribed from PDIA3 cDNA and was used to display PDIA3 mRNA location in rat testes by in situ hybridization. PDIA3 protein distribution was also observed in testis and sperm cells by immunohistochemistry and immunocytochemistry, respectively. The rat PDIA3 transcript and protein were localized in the cells from spermatocytes to the spermatozoa phases of rat testes, mostly in the pachytene spermatocytes. PDIA3 protein was also observed on the intact sperm membrane including the tail. The rat PDIA3 gene is transcribed and translated through the whole spermatogenesis process, and the PDIA3 protein is spread all over the sperm cell membrane. The results provide some primary information about PDIA3 in testis and sperm for further study on PDIA3 function in rat spermatogenesis and sperm-egg fusion. [ABSTRACT FROM AUTHOR]

Constructing carbon nanotubes and related segments with atomic precision remains challenging, despite significant advances, including cycloparaphenylene (CPP), carbon nanobelts, and phenine nanotubes. Here, we report three conjugated nanobelts ( NB1 - NB3 ) constructed by longitudinal π-extension of CPP with rings of the same, smaller, or larger size. Each nanobelt comprises three fused aromatic units bridging two axial CPP rings, which mediate the intermolecular assembly. NB1 - NB3 have a delocalized electronic structure, showing largely red-shifted emission. The smaller NB2 can insert into NB3 to form a stable double-walled assembly ( NB2 ⊃ NB3 ), which exhibits energy transfer with nearly 100% efficiency.

A multicomponent [2+2+1] tandem cyclization of alkynones with amines and water using potassium thiocyanate as electrolyte and raw material to access thiazol-2(3 H )-ones has been developed. This transformation proceeded smoothly via electrocatalytic oxidative C-H bond thiolation, and nucleophilic cascade cyclization to build the (C-S/C-N) bonds to construct the C-O bond. The reaction avoided using transition metal catalysts or oxidation reagents, making it more sustainable and renewable.

Smart nanoplatforms designed for nuclear-targeted delivery of chemotherapeutic agents to tumor sites are pivotal in advancing tumor treatment and immunotherapy. Herein, we introduced a novel nuclear-targeting double-shell smart nanoplatform (HMCuS/Pt/ICG@MnO 2 @9R-P201 (HMCPIM9P)), which synergistically enhances chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), immunotherapy and chemodynamic therapy (CDT). The core of this nanoplatform consists of double-shell multifunctional nanoparticles (HMCuS@MnO 2 ) that enable targeted delivery of the photosensitizer Indocyanine Green (ICG) and the chemotherapeutic agent cisplatin (Pt). By effectively consuming glutathione (GSH), these nanoparticles boost the chemotherapeutic efficacy of Pt. Additionally, the manganese ion (Mn 2+ ) present activate the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) (cGAS-STING) pathway, bolstering adaptive immune responses against tumors and elevating the level of tumor-infiltrating CD8+ T cells. The incorporation of the hepatoma-targeting peptide (9R-P201 peptide) allows the system to exhibit FOXM1 receptor-mediated nuclear targeting properties specifically in hepatocellular carcinoma (HCC). Notably, when combined with near-infrared (NIR) light, HMCPIM9P demonstrated a remarkable tumor inhibition rate of 95.6 %, fostered a robust immune response, and significantly inhibited tumor growth and recurrence. Overall, the smart nanoplatform boasts active nuclear targeting capabilities, enabling the enrichment of chemotherapeutic agents at tumor sites, and holds great potential for synergistic applications in enhancing chemotherapy and immunotherapy for HCC., 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.)

We established an efficient method using high-speed countercurrent chromatography (HSCCC) combined with preparative high-performance liquid chromatography (prep-HPLC) for isolating and purifying Gels emium elegans ( G. elegans ) alkaloids. First, the two-phase solvent system composed of 1% triethylamine aqueous solution/ n -hexane/ethyl acetate/ethanol (volume ratio 4:2:3:2) was employed to separate the crude extract (350 mg) using HSCCC. Subsequently, the mixture that resulted from HSCCC was further separated by Prep-HPLC, resulting in seven pure compounds including: 14-hydroxygelsenicine ( 1 , 12.1 mg), sempervirine ( 2 , 20.8 mg), 19-(R)-hydroxydihydrogelelsevirine ( 3 , 10.1 mg), koumine ( 4 , 50.5 mg), gelsemine ( 5 , 32.2 mg), gelselvirine ( 6 , 50.5 mg), and 11-hydroxyhumanmantenine ( 7 , 12.5 mg). The purity of these seven compounds were 97.4, 98.9, 98.5, 99, 99.5, 96.8, and 85.5%, as determined by HPLC. The chemical structures of the seven compounds were analyzed and confirmed by electrospray ionization mass spectrometry (ESI-MS), 1H-nuclear magnetic resonance (1H NMR), and 13 C-nuclear magnetic resonance (13 C NMR) spectra. The results indicate that the HSCCC-prep-HPLC method can effectively separate the major alkaloids from the purified G. elegans , holding promising prospects for potential applications in the separation and identification of other traditional Chinese medicines.

Background: Polycystic ovary syndrome (PCOS) affects 6-20% of women worldwide, with insulin resistance and hyperinsulinemia occurring in 50-70% of patients. Hyperinsulinemia exacerbates oxidative stress, contributing to PCOS pathogenesis. N-acetylcysteine (NAC) is an antioxidant and insulin sensitizer that shows promise as a therapeutic for PCOS. Our current study aimed to investigate the effects of NAC supplementation on endocrine-metabolic parameters in PCOS mice and its effect on ovulation induction (OI) efficacy in women with PCOS., Methods: Female C57BL/6 mice were orally administered letrozole (LE) to induce PCOS and then randomly divided into groups receiving daily oral administration of 160 mg/kg NAC (PCOS + NAC group), 200 mg/kg metformin (PCOS + Met group), or 0.5% carboxymethyl cellulose (drug solvent) (pure PCOS group) for 12 days. Healthy female mice served as pure controls. Estrous cycles were monitored during the intervention. Metabolic and hormone levels, ovarian phenotypes, antioxidant activity in ovarian tissues, and oxidative stress levels in oocytes were assessed post-intervention. Furthermore, a pragmatic, randomized, controlled clinical study was conducted with 230 PCOS women, randomly assigned to the NAC group (1.8 g/day oral NAC, n = 115) or the control group (n = 115). Patients in both groups underwent ≤ 3 cycles of OI with sequential LE and urinary follicle-stimulating hormone (uFSH). Cycle characteristics and pregnancy outcomes were compared between groups., Results: Similar to metformin, NAC supplementation significantly improved the estrous cycles and ovarian phenotypes of PCOS mice; reduced the LH concentration, LH/FSH ratio, and T level; and increased glucose clearance and insulin sensitivity. Notably, NAC significantly reduced oocyte ROS levels and increased the mitochondrial membrane potential in PCOS mice. Additionally, NAC significantly enhanced enzymatic and nonenzymatic antioxidant activities in PCOS mouse ovaries, whereas metformin had no such effect. In the clinical trial, compared to women in the control group, women receiving NAC had significantly lower average uFSH dosage and duration (p < 0.005) and significantly greater clinical pregnancy rates per OI cycle and cumulative clinical pregnancy rates per patient (p < 0.005)., Conclusion: NAC supplementation improved endocrine-metabolic parameters in PCOS mice and significantly enhanced OI efficacy with sequential LE and uFSH in women with PCOS. Therefore, NAC could be a valuable adjuvant in OI for women with PCOS., (© 2024. The Author(s).)

Reference electrode (RE) plays the core role in accurate potential control in electrochemistry. However, nanoresolved electrochemical characterization techniques still suffer from unstable potential control of pseudo-REs, because the commercial RE is too large to be used in the tiny electrochemical cell, and thus only pseudo-RE can be used. Therefore, microsized RE with a stable potential is urgently required to push the nanoresolved electrochemical measurements to a new level of accuracy and precision, but it is quite challenging to reproducibly fabricate such a micro RE until now. Here, we revisited the working mechanism of the metal-junction RE and clearly revealed the role of the ionic path between the metal wire and the borosilicate glass capillary to maintain a stable potential of RE. Based on this understanding, we developed a method to fabricate micro ultrastable-RE, where a reproducible ultrathin ionic path can form by dissolving a sandwiched sacrificial layer between the Pt wire and the capillary for the ion transfer. The potential of this new micro RE was almost the same as that of the commercial Ag/AgCl electrode, while the size is much smaller. Different from commercial REs that must be stored in the inner electrolyte, the new RE could be directly stored in air for more than one year without potential drift. Eventually, we successfully applied the micro RE in the electrochemical tip-enhanced Raman spectroscopy (EC-TERS) measurement to precisely control the potential of the working electrode, which makes it possible to compare the results from different laboratories and techniques to better understand the electrochemical interface at the nanoscale.

The triglyceride-glucose (TyG) index, a reliable surrogate biomarker of insulin resistance (IR), is highlighted recently as related to cardiac disorders. However, the associations of the TyG index and its combination with blood pressure (BP) on cardiovascular and all-cause mortality in hypertension remain unclear. In this study, we included 9,635 hypertension patients from the National Health and Nutrition Examination Survey 1999-2018. During a median follow-up of 8.00 years, a total number of 853 and 2,489 in cardiovascular and all-cause deaths occurred, respectively. After full adjustments, the individual TyG index was positively associated with cardiovascular and all-cause mortality with J-shaped dose-response relationships. The lowest risk thresholds of the TyG index for cardiovascular and all-cause mortality were 9.5551 and 9.3405, respectively. In joint analyses, the highest risks of cardiovascular and all-cause mortality were observed among those with elevated levels of both BP and IR [1.64 (1.18, 2.28), P = 0.0031; 1.39 (1.14, 1.70), P = 0.0011; respectively]. In sensitivity and subgroup analyses, the results were generally robust. Our data appeal a hypothesis that future treatments for hypertension may require a combination of BP controlled and IR improvement., 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 © 2024 Xu, Peng, Guo, Zhao, Chen, Mai, Tan, Chen, Zeng and Zhang.)

Materials and their interfaces are the core for the development of a large variety of fields, including catalysis, energy storage and conversion. In this case, tip-enhanced Raman spectroscopy (TERS), which combines scanning probe microscopy with plasmon-enhanced Raman spectroscopy, is a powerful technique that can simultaneously obtain the morphological information and chemical fingerprint of target samples at nanometer spatial resolution. It is an ideal tool for the nanoscale chemical characterization of materials and interfaces, correlating their structures with chemical performances. In this review, we begin with a brief introduction to the nanoscale characterization of materials and interfaces, followed by a detailed discussion on the recent theoretical understanding and technical improvements of TERS, including the origin of enhancement, TERS instruments, TERS tips and the application of algorithms in TERS. Subsequently, we list the key experimental issues that need to be addressed to conduct successful TERS measurements. Next, we focus on the recent progress of TERS in the study of various materials, especially the novel low-dimensional materials, and the progresses of TERS in studying different interfaces, including both solid-gas and solid-liquid interfaces. Finally, we provide an outlook on the future developments of TERS in the study of materials and interfaces.

A new copper and electrocatalytic synergy strategy for efficiently constructing fused quinazolinones has been developed. In the presence of cupric acetate and oxygen, aryl ketones and 1,2,3,4-tetrahydroisoquinoline can smoothly participate in this transformation, thus providing a variety of substituted quinazolones in an undivided cell. The reaction shows good functional group tolerance and provides universal quinazolinones at a good yield under mild conditions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: With the continued prevalence of COVID-19, repeated infection caused by SARS-CoV-2 has become common. However, studies on immune persistence post Omicron XBB reinfection are limited., Methods: We prospectively studied the durability and cross-reactivity of neutralizing antibodies (NAbs) and T cell responses among 20 subjects who suffered Omicron BA.5 infection with or without Omicron XBB reinfection over 6-month through the pseudovirus neutralization test and the fluorospot assay., Results: NAbs against EG.5.1, BA.2.86, and JN.1 subvariants were decreased and undetectable at 6-month post Omicron BA.5 infection, while those elicited by Omicron XBB reinfection were significant increased and remained detectable against all detected variants within 6-month. Furthermore, in subjects with Omicron XBB reinfection, memory T cell responses could cross-recognized wild-type and Omicron spike peptides and reached peak at 3-month. Interestingly, comparable robust T cell responses were observed among non-seroconverted subjects post Omicron XBB exposure., Conclusion: Though the NAbs against various emerging Omicron subvariants elicited by Omicron XBB reinfection can persist for at least 6-month, the HCWs should strengthen personal protection and timely be immunized with updated vaccines upon current circulating variants or conserved T epitope., 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 © 2024 Zhao, Li, Zhang, Chen, Zhao, Wu, Wang, Xu, Lv, Jiang, Wang and Fang.)

Background: Endometrial cancer is one of the most common female cancers globally and in China. Although timely assessment of 5-year relative survival is crucial for guiding secondary prevention and early screening programs for endometrial cancer patients, those kinds of data are scarce in China. We aimed to provide a timely and accurate assessment of 5-year relative survival for patients with endometrial cancer from eastern China., Methods: Overall, 945 patients diagnosed with endometrial cancer during 2004 - 2018 from four cancer registries with high-quality data from Taizhou, eastern China were included. Period analysis was used to calculate 5-year relative survival for overall and the stratification by age at diagnosis and region. Model-based period analysis was used to predict the 5-year relative survival for the upcoming period of 2019 - 2023., Results: We found that 5-year relative survival during 2014 - 2018 reached 86.4% for overall, while urban areas had higher survival compared to rural areas (91.3% vs. 85.3%). Furthermore, there was a clear age gradient, decreasing from 89.3% for age < 55 years to 80.5% for age > 74 years. Predicted 5-year relative survival for the upcoming period 2019 - 2023 could reach 88.4%., Conclusions: We provide, a timely and accurate assessment of 5-year relative survival for patients with endometrial cancer from Taizhou, eastern China, reaching 86.4% for overall. Our finding has important implications for the overall evaluation of early detection and screening programs for patients with endometrial cancer in eastern China., Competing Interests: None to declare., (Copyright 2024, Zhao et al.)

Designing high-entropy oxyhydroxides (HEOs) electrocatalysts with controlled nanostructures is vital for efficient and stable water-splitting electrocatalysts. Herein, a novel HEOs material (FeCoNiWCuOOH@Cu) containing five non-noble metal elements derived by electrodeposition on a 3D double-continuous porous Cu support is created. This support, prepared via the liquid metal dealloying method, offers a high specific surface area and rapid mass/charge transfer channels. The resulting high-entropy FeCoNiWCuOOH nanosheets provide a dense distribution of active sites. The heterostructure between Cu skeletons and FeCoNiWCuOOH nanosheets enhances mass transfer, electronic structure coupling, and overall structural stability, leading to excellent activities in the oxygen evolution reaction (OER), hydrogen evolution reaction (HER), and water splitting reaction. At 10 mA cm -2 , the overpotentials for OER, HER, and water splitting in 1.0 m KOH solution are 200, 18, and 1.40 V, respectively, outperforming most current electrocatalysts. The catalytic performance remains stable even after operating at 300 mA cm -2 for 100, 100, and over 1000 h, correspondingly. This material has potential applications in integrated hydrogen energy systems. More importantly, density functional theory (DFT) calculations demonstrate the synergy of the five elements in enhancing water-splitting activity. This work offers valuable insights for designing industrial water electrolysis systems., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Paclitaxel (PTX) serves as a primary chemotherapy agent against diverse solid tumors including breast cancer, lung cancer, head and neck cancer and ovarian cancer, having severe adverse effects including PTX-induced peripheral neuropathy (PIPN) and hypersensitivity reactions (HSR). A recommended anti-allergic agent diphenhydramine (DIP) has been used to alleviate PTX-induced HSR. Desloratadine (DLT) is a third generation of histamine H 1 receptor antagonist, but also acted as a selective antagonist of 5HTR 2A . In this study we investigated whether DLT ameliorated PIPN-like symptoms in mice and the underlying mechanisms. PIPN was induced in male mice by injection of PTX (4 mg/kg, i.p.) every other day for 4 times. The mice exhibited 50% reduction in mechanical threshold, paw thermal response latency and paw cold response latency compared with control mice. PIPN mice were treated with DLT (10, 20 mg/kg, i.p.) 30 min before each PTX administration in the phase of establishing PIPN mice model and then administered daily for 4 weeks after the model was established. We showed that DLT administration dose-dependently elevated the mechanical, thermal and cold pain thresholds in PIPN mice, whereas administration of DIP (10 mg/kg, i.p.) had no ameliorative effects on PIPN-like symptoms. We found that the expression of 5HTR 2A was selectively elevated in the activated spinal astrocytes of PIPN mice. Spinal cord-specific 5HTR 2A knockdown by intrathecal injection of AAV9-5Htr2a-shRNA significantly alleviated the mechanical hyperalgesia, thermal and cold hypersensitivity in PIPN mice, while administration of DLT (20 mg/kg) did not further ameliorate PIPN-like symptoms. We demonstrated that DLT administration alleviated dorsal root ganglion neuronal damage and suppressed sciatic nerve destruction, spinal neuron apoptosis and neuroinflammation in the spinal cord of PIPN mice. Furthermore, we revealed that DLT administration suppressed astrocytic neuroinflammation via the 5HTR 2A /c-Fos/NLRP3 pathway and blocked astrocyte-neuron crosstalk by targeting 5HTR 2A . We conclude that spinal 5HTR 2A inhibition holds promise as a therapeutic approach for PIPN and we emphasize the potential of DLT as a dual-functional agent in ameliorating PTX-induced both PIPN and HSR in chemotherapy. In summary, we determined that spinal 5HTR 2A was selectively activated in PIPN mice and DLT could ameliorate the PTX-induced both PIPN- and HSR-like pathologies in mice. DLT alleviated the damages of DRG neurons and sciatic nerves, while restrained spinal neuronal apoptosis and CGRP release in PIPN mice. The underlying mechanisms were intensively investigated by assay against the PIPN mice with 5HTR 2A -specific knockdown in the spinal cord by injection of adeno-associated virus 9 (AAV9)-5Htr2a-shRNA. DLT inhibited astrocytic NLRP3 inflammasome activation-mediated spinal neuronal damage through 5HTR 2A /c-FOS pathway. Our findings have supported that spinal 5HTR 2A inhibition shows promise as a therapeutic strategy for PIPN and highlighted the potential advantage of DLT as a dual-functional agent in preventing against PTX-induced both PIPN and HSR effects in anticancer chemotherapy., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

A great number of COVID-19 patients was caused by Omicron BA.5 subvariant between December 2022 and January 2023 after the end of the zero-COVID-19 policy in China. In this study, we clarified the epidemiological and immunological characteristics of 457 enrolled middle-aged and elderly population in two housing estates after Omicron BA.5 wave. A total of 89.9 % (411/457) individuals have suffered Omicron BA.5 infection, among which 78.1 % (321/411) were symptomatic. The elderly patients were more likely to show fatigue and had longer symptomatic period than that of middle-aged patients post Omicron BA.5 infection. Omicron XBB and BA.2.86 subvariants extensively escaped the immunity elicited by Omicron BA.5 infection. The level of neutralizing antibody was mostly affected by vaccination doses rather than underlying disease status in these participants. It is very important to strengthen the epidemiological investigation and immune resistance assessment among elderly population for control of emerging SARS-CoV-2 variants., 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., (© 2024 The Authors.)

The utilization of axially chiral biaryl diamines has been widely acknowledged as highly advantageous structures for the advancement of chiral catalysts and ligands. This highlights their extensive range of applications in asymmetric catalysis and synthesis. Herein, we devised a direct arylation reactions of 5-aminopyrazoles with azonaphthalenes, utilizing chiral phosphoric acid as the catalyst. This method delivers structurally novel atroposelective N, N-1,2-azole heteroaryl diamines with high yields (up to >98 %) and good to excellent enantiomeric ratios while exhibiting a wide range of substrate compatibility., (© 2024 Wiley-VCH GmbH.)

A novel electrocatalytic dimerization of o -aminphenols and a hydrogen borrowing-like cascade for synthesizing N-monoalkylated aminophenoxazinones have been developed. This electrocatalytic reaction uses a constant current mode in an undivided cell and is free of metal catalysis, open to the air, and eco-friendly. In particular, this protocol exhibits a wide substrate range and provides versatile N-monoalkylated aminophenoxazinones in medium to good yields. The results of our mechanistic research reveal that this protocol involves a cascade of electrochemical cyclocondensation of o -aminphenols and the hydrogen transfer process via paired electrolysis.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial activation and neuroinflammation are key cellular events that determine the outcome of TBI, especially neuronal and cognitive function. Studies have suggested that the metabolic characteristics of microglia dictate their inflammatory response. The pyruvate kinase isoform M2 (PKM2), a key glycolytic enzyme, is involved in the regulation of various cellular metabolic processes, including mitochondrial metabolism. This suggests that PKM2 may also participate in the regulation of microglial activation during TBI. Therefore, the present study aimed to evaluate the role of PKM2 in regulating microglial activation and neuroinflammation and its effects on cognitive function following TBI. A controlled cortical impact (CCI) mouse model and inflammation-induced primary mouse microglial cells in vitro were used to investigate the potential effects of PKM2 inhibition and regulation. PKM2 was significantly increased during the acute and subacute phases of TBI and was predominantly detected in microglia rather than in neurons. Our results demonstrate that shikonin and TEPP-46 can inhibit microglial inflammation, improving mitochondria, improving mouse behavior, reducing brain defect volume, and alleviating pathological changes after TBI. There is a difference in the intervention of shikonin and TEPP-46 on PKM2. Shikonin directly inhibits General PKM2; TEPP-46 can promote the expression of PKM2 tetramer. In vitro experiments, TEPP-46 can promote the expression of PKM2 tetramer, enhance the interaction between PKM2 and MFN2, improve mitochondria, alleviate neuroinflammation. General inhibition and tetramerization activation of PKM2 attenuated cognitive function caused by TBI, whereas PKM2 tetramerization exhibited a better treatment effect. Our experiments demonstrated the non-metabolic role of PKM2 in the regulation of microglial activation following TBI. Both shikonin and TEPP-46 can inhibit pro-inflammatory factors, but only TEPP-46 can promote PKM2 tetramerization and upregulate the release of anti-inflammatory factors from microglia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus-specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS-CoV-2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post-BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2- and CH.1.1-spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus-specific memory T cells, even among the non-seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS-CoV-2 variants among adolescents., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: While timely assessment of long-term survival for patients with bone cancer is essential for evaluation on early detection and prognosis level of treatment of bone cancer, those data are extremely scarce in China. We aimed to timely and accurately assess long-term survival for patients with bone cancer in Eastern China., Methods: Patients diagnosed with bone cancer during 2004 - 2018 from four cancer registries with high-quality data from Taizhou, Eastern China were included. Five-year relative survival (RS) of bone cancer patients was calculated by period analysis for overall and the stratification. We further predicted 5-year RS during upcoming 2019 - 2023 using a model-based period analysis and survival data during 2004 - 2018., Results: Overall, 5-year RS for patients with bone cancer during 2014 - 2018 reached 46.6%, being 40.8% for male and 51.0% for female. Five-year RS declined along with aging, decreasing from 58.9% for age < 45 years to 41.5% for age > 60 years, while 5-year RS for urban area was higher compared to rural area (59.1% vs. 44.3%). The 5-year RS during upcoming 2019 - 2023 reached 48.3%. We found a clear upward trend in 5-year RS during 2004 - 2023 for overall and the stratification by sex, age at diagnosis, and region., Conclusions: We found that, for first time in China using period analysis, most up-to-date 5-year RS for patients with bone cancer reached 46.6% during 2014 - 2018, and is projected to reach 48.3% for the period 2019 - 2023, which has important implications for timely evaluation on early detection and prognosis level of treatment for patients with bone cancer in Eastern China., Competing Interests: None to declare., (Copyright 2024, Xie et al.)

Collective excitations including plasmons, magnons, and layer-breathing vibration modes emerge at an ultralow frequency (<1 THz) and are crucial for understanding van der Waals materials. Strain at the nanoscale can drastically change the property of van der Waals materials and create localized states like quantum emitters. However, it remains unclear how nanoscale strain changes collective excitations. Herein, ultralow-frequency tip-enhanced Raman spectroscopy (TERS) with sub-10 nm resolution under ambient conditions is developed to explore the localized collective excitation on monolayer semiconductors with nanoscale strains. A new vibrational mode is discovered at around 12 cm -1 (0.36 THz) on monolayer MoSe 2 nanobubbles and it is identified as the radial breathing mode (RBM) of the curved monolayer. The correlation is determined between the RBM frequency and the strain by simultaneously performing deterministic nanoindentation and TERS measurement on monolayer MoSe 2 . The generality of the RBM in nanoscale curved monolayer WSe 2 and bilayer MoSe 2 is demonstrated. Using the RBM frequency, the strain of the monolayer MoSe 2 on the nanoscale can be mapped. Such an ultralow-frequency vibration from curved van der Waals materials provides a new approach to study nanoscale strains and points to more localized collective excitations to be discovered at the nanoscale., (© 2024 Wiley‐VCH GmbH.)

Objective: To investigate the impact of non-high-density lipoprotein cholesterol (non-HDL-C) level on major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality in the Kailuan Study cohort undergoing revascularization. Methods: This is a prospective cohort study, with participants from the Kailuan Study cohort who participated in physical examinations from 2006 to 2020 and received revascularization therapy for the first time. According to the level of non-HDL-C, the study subjects were divided into 3 groups:<2.6 mmol/L group, 2.6-<3.4 mmol/L group, and≥3.4 mmol/L group. Annual follow-up was performed, and the endpoint events were MACCE and all-cause mortality. Cox proportional regression model was implemented to estimate the impact on MACCE and all-cause mortality associated with the different non-HDL-C groups. The partial distributed risk model was used to analyze the impact of different non-HDL-C levels on MACCE event subtypes, and death was regarded as a competitive event. The restricted cubic spline regression model was used to explore the dose-response relationship between non-HDL-C level and all-cause mortality, MACCE and its subtypes. Results: A total of 2 252 subjects were enrolled in the study, including 2 019 males (89.65%), aged (62.8±8.3) years, the follow-up time was 5.72 (3.18, 8.46) years. There were 384 cases(17.05%) of MACCE and 157 cases(6.97%) of all-cause mortality. Compared with patients with non-HDL-C≥3.4 mmol/L, patients with non-HDL-C<2.6 mmol/L were associated with a 38% reduced risk of MACCE after revascularization [ HR =0.62(95% CI : 0.48-0.80)]. Every 1 mmol/L decrease in non-HDL-C was associated with a 20% reduction in the risk of MACCE [ HR =0.80(95% CI : 0.73-0.88)]. The results of restricted cubic spline also showed that non-HDL-C levels after revascularization therapy were positively correlated with MACCE events (overall association P <0.001, non-linear association P =0.808). For all-cause mortality, compared to the non-HDL-C≥3.4 mmol/L group, the HR for all-cause mortality after revascularization in non-HDL-C<2.6 mmol/L group was 0.67(95% CI : 0.46-1.01). Every 1 mmol/L decrease in non-HDL-C was associated with a 15% reduction in the risk of all-cause mortality [ HR =0.85(95% CI : 0.73-0.99)]. The restricted cubic spline results showed a linear association between non-HDL-C levels after revascularization therapy and the risk of all-cause mortality (overall association P =0.039, non-linear association P =0.174). Conclusion: The decrease in non-HDL-C levels after revascularization were significantly associated with a reduced risk of MACCE and all-cause mortality.

Here we report B(C 6 F 5 ) 3/ CPA-catalyzed enantioselective aza-Diels-Alder reaction of 3,3-difluoro-2-Aryl-3H-indoles with unactivated dienes to access chiral 10,10-difluoro-tetrahydropyrido[1,2-a]indoles. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 10,10-difluoro-tetrahydropyrido[1,2-a]indole skeleton was successfully achieved without any reduction in both yield and enantioselectivity., (© 2024 Wiley-VCH GmbH.)

The emergence of novel Omicron subvariants has raised concerns regarding the efficacy of immunity induced by prior Omicron subvariants breakthrough infection (BTI) or reinfection against current circulating Omicron subvariants. Here, we prospectively investigated the durability of antibody and T cell responses in individuals post Omicron BA.2.2 BTI, with or without subsequent Omicron BA.5 reinfection. Our findings reveal that the emerging Omicron subvariants, including CH.1.1, XBB, and JN.1, exhibit extensive immune evasion induced by previous infections. Notably, the level of IgG and neutralizing antibodies were found to correlate with subsequent Omicron BA.5 reinfection. Fortunately, T cell responses recognizing both Omicron BA.2 and CH.1.1 peptides were observed. Furthermore, Omicron BA.5 reinfection may alleviate immune imprinting induced by WT-vaccination, bolster virus-specific ICS + T cell responses, and promote the phenotypic differentiation of virus-specific memory CD8 + T cells. Antigen-updated or T cell-conserved vaccines are needed to control the transmission of diverse emerging SARS-CoV-2 variants., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

With the continuous rise of environmental pollution and energy crisis, the global energy revolution is risen. Development of renewable blue energy based on the emerging promising triboelectric nanogenerators (TENG) has become an important direction of future energy development. The solid-liquid contact triboelectric nanogenerator (TENG) has the advantages of flexible structure, easy manufacture, and long-term stability, which makes it easier to integrate and achieve large-scale conversion of wave mechanical energy. However, the electric power output is still not large enough, which limits its practical applications. In this work, a nanocomposite electret layer enhanced solid-liquid contact triboelectric nanogenerator (E-TENG) is proposed for water wave energy harvesting, which can effectively improve the electric output and achieve real-time power supply of wireless sensing. Through introducing a nanocomposite electret layer into flexible multilayer solid-liquid contact TENG, higher power output is achieved. The E-TENG (active size of 50 mm × 49 mm) shows desired output performance, a power density of 521 mW m -2 . The generated electric energy can drive wireless temperature sensing by transmitting wireless signals carrying detection information at the period of ˂5.5 min. This research greatly improves the electric output and provides a solid basis for the industrialization of TENG in blue energy., (© 2023 Wiley‐VCH GmbH.)

An unprecedented solvent-tuned electrochemical method for selective C(sp 3 )-H bond activation towards the synthesis of C3 functionalized chromone derivatives has been developed. This electrosynthesis protocol provides an efficient and green way to access various C3-functionalized chromones by avoiding traditionally employed transition metals and high temperatures. The swappable chemoselectivity was controlled mainly by altering the solvent and the current. A plausible reaction mechanism has been proposed with the help of radical capture and cyclic voltammetry experiments.

After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

There is growing interest in developing a high-performance self-supervised denoising algorithm for real-time chemical hyperspectral imaging. With a good understanding of the working function of the zero-shot Noise2Noise-based denoising algorithm, we developed a self-supervised Signal2Signal (S2S) algorithm for real-time denoising with a single chemical hyperspectral image. Owing to the accurate distinction and capture of the weak signal from the random fluctuating noise, S2S displays excellent denoising performance, even for the hyperspectral image with a spectral signal-to-noise ratio (SNR) as low as 1.12. Under this condition, both the image clarity and the spatial resolution could be significantly improved and present an almost identical pattern with a spectral SNR of 7.87. The feasibility of real-time denoising during imaging was well demonstrated, and S2S was applied to monitor the photoinduced exfoliation of transition metal dichalcogenide, which is hard to accomplish by confocal Raman spectroscopy. In general, the real-time denoising capability of S2S offers an easy way toward in situ/in vivo/operando research with much improved spatial and temporal resolution. S2S is open-source at https://github.com/3331822w/Signal2signal and will be accessible online at https://ramancloud.xmu.edu.cn/tutorial.

Poly(ionic liquid) (PIL)-based porous membranes are extensively investigated as soft polymer actuators. While PILs have shown significant advancements in membrane fabrication and stabilization of metal nanoparticles (MNPs), research on integrating MNPs into porous membranes to achieve actuation behavior under multiple stimuli is limited. Herein, this work presents a new paradigm for designing a porous PIL-polyacrylic acid (PAA) membrane with a distinct MNP gradient via a top-bottom diffusion approach involving a metal salt precursor solution and NaBH 4 as a reducing agent. The strong binding sites provided by PILs, combined with the gradient distribution of -COO - groups across the membrane cross-section, play a significant role in controlling the MNPs' gradient distribution. Interestingly, the MNPs within the membrane display excellent catalytic activity in exothermic reactions such as H 2 O 2 decomposition, dissipating uneven heat that quickly permeates the membrane network. This induces asymmetrical swelling of polymer chains, resulting in rapid membrane bending. Furthermore, such MNP-loaded membrane could serve as a portable test paper for visually monitoring H 2 O 2 . This advancement paves the way for the development of intricate smart actuation materials and expands their practical applications in various real-life scenarios., (© 2024 Wiley‐VCH GmbH.)

Aim: To evaluate the role of semaphorin 7A (Sema7A) and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells (HCEs)., Methods: Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0, 125, 250, or 500 ng/mL for 24, 48, or 72h in vitro . Transepithelial electrical resistance (TEER) as well as Dextran-fluorescein isothiocyanate (FITC) permeability assays were conducted to assess barrier function. To quantify tight junctions (TJs) such as occludin and zonula occludens-1 (ZO-1) at the mRNA level, reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed. Immunoblotting was used to examine the activity of the nuclear factor-kappa B (NF-κB) signaling pathway and the production of TJs proteins. Immunofluorescence analyses were employed to localize the TJs. Enzyme-linked immunosorbent assay (ELISA) and RT-PCR were utilized to observe changes in interleukin (IL)-1β levels. To investigate the role of NF-κB signaling activation and IL-1β in Sema7A's anti-barrier mechanism, we employed 0.1 µmol/L IκB kinase 2 (IKK 2 ) inhibitor IV or 500 ng/mL IL-1 receptor (IL-1R) antagonist., Results: Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time- and dose-dependent manner, as well as altering the localization of TJs. Furthermore, Sema7A stimulated the activation of inhibitor of kappa B alpha (IκBα) and expression of IL-1β. The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK 2 inhibitor IV or IL-1R antagonists., Conclusion: Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins, as well as the expression of IL-1β. These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium., Competing Interests: Conflicts of Interest: Yang CC, None; Yang XX, None; Zhao XJ, None; Wang H, None; Guo ZH, None; Jin K, None; Liu Y, None; Li BH, None., (International Journal of Ophthalmology Press.)

5F-MDMB-PICA, an indole-type synthetic cannabinoid (SC), was classified illicit globally in 2020. Although the extensive metabolism of 5F-MDMB-PICA in the human body warrants the development of robust analytical methods for metabolite detection and quantification, a current lack of reference standards for characteristic metabolites hinders such method creation. This work described the synthesis of 18 reference standards for 5F-MDMB-PICA and its possible Phase I metabolites, including three hydroxylated positional isomers R14 to R16. All the compounds were systematic characterized via nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. Furthermore, two methods were developed for the simultaneous detection of all standards using liquid chromatography-tandem mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. By comparison with authentic samples, R17 was identified as a suitable urine biomarker for 5F-MDMB-PICA uptake., (© 2024 John Wiley & Sons Ltd.)

An electrochemical multicomponent [2+2+1] cascade cyclization of enaminones and primary amines towards the synthesis of 4-acylimidazoles has been developed. In an undivided cell, enaminones and primary amines can smoothly participate in this reaction to provide a series of 1,2-disubstituted 4-acylimidazoles at room temperature. The reaction avoids the use of both transition-metal catalysts and oxidation reagents, which makes it more sustainable and renewable.