Search

Qian Huang,1,&ast; Xing Chen,1,2,&ast; Hui Yan Shen,1 Jia Mou Zhou,1 He Qiao Zhang,1 Li Wang,1 Ren Chen,1 Jing Cheng,1 Yan Zhang,1 Dong Mei Zhang,1 Gui Mei Chen1 1School of Health Service Management, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2School of Public Health, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gui Mei Chen; Dong Mei Zhang, Email chengm@ahmu.edu.cn; zdmd@sina.comPurpose: We aimed to analyze the relationship between handgrip strength/relative handgrip strength among older Han adults with type 2 diabetes mellitus (T2DM) by gender to determine the optimal cut-off value of grip strength for older adults.Methods: A multi-stage sampling method was used to conduct a questionnaire survey and physical examination of 6128 older adults in Anhui Province. Chi-squares tests, t-tests, analysis of variance, and logistic regression analysis were used to analyze the association between handgrip strength/relative handgrip strength and T2DM between the sexes. The decision tree model (CRT) was used to explore the predictive value of handgrip strength /relative handgrip strength on T2DM.Results: There was an association between handgrip strength and T2DM (P = 0.006, OR = 0.985, 95% CI = 0.975, 0.996), which was found in females (P = 0.013, OR = 0.978, 95% CI = 0.961, 0.995) but not in males (P = 0.125, OR = 0.989, 95% CI = 0.976, 1.003). Relative handgrip strength was also correlated with T2DM (P = 0.014, OR = 0.730, 95% CI = 0.568, 0.939), which was found in females (P = 0.003, OR = 0.534, 95% CI = 0.352, 0.809) but not in males (P = 0.432, OR = 0.879, 95% CI = 0.638, 1.212). The incidence of T2DM in elderly females with hypertension who were uneducated and with a handgrip strength of < 17.350 kg was 24.3% (115 cases), whereas that in elderly females with hypertension and a relative handgrip strength of < 0.240 was 29.0% (127 cases).Conclusion: According to our results, handgrip strength and relative handgrip strength were associated with T2DM. People with hypertension had a higher risk of T2DM in women with a handgrip strength of ≤ 17.350kg and a relative grip strength of ≤ 0.240. Further research is needed to validate the effectiveness of this cut-off for implementing interventions and avoiding risks.Keywords: diabetes mellitus, handgrip strength, gender, older adult

An-Hai Li,1 Wen-Wen Li,2 Xiao-Qian Yu,3 Dai-Ming Zhang,4 Yi-Ran Liu,5 Ding Li1 1Department of Dermatology, Qingdao Huangdao District Central Hospital, Qingdao, People’s Republic of China; 2Department of Hematology, Qingdao Women and Children’s Hospital, Qingdao, People’s Republic of China; 3Department of Dermatology, Qingdao Haici Hospital (Qingdao Traditional Chinese Medicine Hospital), Qingdao, People’s Republic of China; 4Department of Pharmacy, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 5College of Traditional Chinese Medicine, Weifang Medical College, Weifang, People’s Republic of ChinaCorrespondence: Ding Li, Department of Dermatology, Qingdao Huangdao District Central Hospital, Qingdao, People’s Republic of China, Email 907325791@qq.comBackground: Psoriasis is a recurrent, chronic, inflammation- and immune-mediated skin disease with multiple causative factors. However, the genetic markers associated with recurrence have not yet been fully elucidated. Accordingly, in this study, we aimed to identify markers associated with the recurrence of psoriasis.Methods: We analyzed differentially expressed genes to determine which targets were associated with the recurrence of psoriasis and used these data to construct a protein-protein interaction network using Cytoscape software. The results were then validated by analysis of core targets using Gene Expression Omnibus (GEO) datasets and clinical samples. Functional enrichment analysis was used to explore the potential mechanisms mediating the recurrence of psoriasis.Results: We screened out six core targets that played important roles in recurrence of psoriasis, and validation of GEO datasets and clinical samples showed that the expression levels of five core targets were higher in patients with psoriasis than in healthy individuals. Functional enrichment analysis revealed that the cell cycle and oocyte meiosis signaling pathways were involved in the recurrence of psoriasis.Conclusion: Our findings provided insights into the mechanisms mediating the onset and recurrence of psoriasis.Keywords: psoriasis, recurrence, cell cycle, gene expression profiling, pathogenic mechanism

YueLong Wang,1,2,* Gang Guo,1,* HaiFeng Chen,2 Xiang Gao,1 RangRang Fan,1 DongMei Zhang,1 LiangXue Zhou2 1State Key Laboratory of Biotherapy and Cancer Center, 2Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China *These authors contributed equally to this paper Abstract: The aim of this study was to develop a kind of osteogenic biodegradable composite graft consisting of human placenta-derived mesenchymal stem cell (hPMSC) material for site-specific repair of bone defects and attenuation of clinical symptoms. The novel nano- to micro-structured biodegradable hybrid fibers were prepared by electrospinning. The characteristics of the hybrid membranes were investigated by a range of methods, including Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. Morphological study with scanning electron microscopy showed that the average fiber diameter and the number of nanoscale pores on each individual fiber surface decreased with increasing concentration of poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCEC). The prepared polylactide (PLA)/PCEC fibrous membranes favored hPMSC attachment and proliferation by providing an interconnected, porous, three-dimensional mimicked extracellular environment. What is more, hPMSCs cultured on the electrospun hybrid PLA/PCEC fibrous scaffolds could be effectively differentiated into bone-associated cells by positive alizarin red staining. Given the good cellular response and excellent osteogenic potential in vitro, the electrospun PLA/PCEC fibrous scaffolds could be one of the most promising candidates for bone tissue engineering. Keywords: electrospinning, PLA, PCEC, hPMSCs, bone tissue engineering

PURPOSE: The present clinical study assessed the feasibility of extensive pedicled supraclavicular fasciocutaneous island flaps combined with extended vertical lower trapezius island myocutaneous flaps for large, full-thickness cheek defect reconstruction after ablative oral cancer surgery. PATIENTS AND METHODS: A retrospective review of data from consecutive patients requiring extensive pedicled supraclavicular fasciocutaneous island flaps and the extended vertical lower trapezius island myocutaneous flap to provide both an inner and an outer lining for major full-thickness cheek defects after oncologic resection. RESULTS: Eight patients had advanced oral squamous cell carcinoma. All patients had combined bone and extensive soft-tissue defects. The extensive pedicled supraclavicular fasciocutaneous island flap with a skin paddle measuring 10 x 8 cm to 14 x 10 cm and the extended vertical lower trapezius island myocutaneous flap with a skin paddle measuring 25 x 10 cm to 15 x 8 cm were used to reconstruct the major through-and-through defects. No major complications occurred in any patient. The patients were followed up for 6 to 20 months; 6 patients were living with no evidence of disease, 1 was living with disease, and 1 had died of local recurrence. CONCLUSIONS: The combined use of the extensive pedicled supraclavicular fasciocutaneous island flap with an extended vertical lower trapezius island myocutaneous flap to reconstruct major through-and-through cheek soft defects is reliable and an excellent alternative to other pedicles, even microsurgical free flaps, for patients who have previously undergone radiotherapy and surgery of the head and neck. [ABSTRACT FROM AUTHOR]

PURPOSE: This clinical study assessed the reverse facial artery-submental artery mandibular osteomuscular flap with titanium dental implants for the functional reconstruction of maxillary defects. PATIENTS AND METHODS: Class 2a defects in 5 patients were repaired with a reverse facial artery-submental artery mandibular osteomuscular flap with titanium dental implants (n = 21). All patients received a fixed partial denture after a 3- to 6-month healing period. RESULTS: All lesions were widely excised in an area extending to the maxilla. Of the implants, 20 (95.2%) were loaded and 1 was lost before loading. Reconstruction with a fixed partial denture was successful in all patients. The patients were followed up for 12 to 20 months (mean, 15.8 months), and no recurrence was observed. CONCLUSION: The reverse facial artery-submental artery mandibular osteomuscular flap with titanium dental implants is safe, quick, and simple to elevate and is reliable for the functional reconstruction of maxillary defects. [ABSTRACT FROM AUTHOR]

Background: Rabies is a major public-health problem in developing countries such as China. Although the recent re-emergence of human rabies in China was noted in several epidemiological studies, little attention was paid to the reasons behind this phenomenon paralleling the findings of the previous reports. The purpose of this study is thus first to characterize the current trends of human rabies in China from 1990 to 2007, and then to define better recommendations for improving the post-exposure prophylaxis (PEP) schedules delivered to rabies patients.Methods: The most updated epidemiological data for 22527 human rabies cases from January 1990 to July 2007, retrieved from the surveillance database of reportable diseases managed by the Ministry of Health of China, were analysed. To investigate the efficiency for the post-exposure treatment of rabies, the details of 244 rabies patients, including their anti-rabies treatment of injuries or related incidents, were ascertained in Guangdong provincial jurisdiction. The risk factors to which the patients were predisposed or the regimens given to 80 patients who received any type of PEP were analysed to identify the reasons for the PEP failures.Results: The results from analysis of the large number of human rabies cases showed that rabies in China was largely under control during the period 1990-1996. However, there has been a large jump in the number of reported rabies cases since 2001 up to a new peak (with an incidence rate of 0.20 per 100000 people) that was reached in 2004, and where the level has remained until present. Then, we analysed the PEP in 244 rabies cases collected in the Guangdong province in 2003 and 2004, and found that 67.2% of the patients did not seek medical services or did not receive any PEP. Further analysis of PEP for the 80 rabies patients who received any type of PEP indicated that almost all of the patients did not receive proper or timely treatment on the wounds or post-exposure vaccination or rabies immunoglobulins.Conclusion: While the issue of under-reporting of rabies in previous years may well be a factor in the apparent upwards trend of human rabies in recent years, the analysis of PEP in the Guangdong province provides evidence that suggests that the failure to receive PEP was a major factor in the number of human cases in China. Thus, the data underline the need for greatly improved availability and timely application of high-quality anti-rabies biologicals, both vaccines and immunoglobulins, in the treatment of human bite victims. Controlling dog rabies through pet vaccination schemes may also play a huge role in reducing the rate of human exposure. Education of the public, health care staff and veterinarians will also help to change the current situation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the repair effect of human umbilical cord blood mesenchymal stem cells (hUCB-MSC) on endometrium of intrauterine adhesion (IUA) by establishing animal model. Methods: Eighteen healthy female New Zealand white rabbits were divided into a control group, an IUA group and an hUCB-MSC transplantation group according to random number table method. The control group underwent laparotomy only. The IUA group underwent IUA modeling surgery using curettage and lipopolysaccharide (LPS) cotton placed in uterine cavity for double injury. The hUCB-MSC transplantation group received the same IUA modeling surgery followed by multipoint injection of hUCB-MSC suspension (2×10 6 cells/ml, 500 μl) into the bilateral uterine myometrium one week after surgery. Four weeks after the IUA modeling surgery, the rabbits were euthanized and samples were collected. Hematoxylin and eosin (HE) staining and Masson staining were used to assess the number of endometrial glands and the fibrosis rate. RNA sequencing was performed on the endometrium of the IUA group and hUCB-MSC transplantation group.The mRNA and protein expression of the fibrosis markers [transforming growth factor β1 (TGF-β1) and tissue inhibitors of metalloproteinase 1 (TIMP1)] and RNA sequencing-related parameters were detected by quantitative real-time PCR (qRT-PCR) and Western blot. Results: Compared with the control group, the number of glands in IUA group decreased (26.33±1.53 vs 4.33±1.53, P <0.001), and the fibrosis rate increased (18.01%±2.21% vs 69.55%±2.42%, P <0.001), indicating successful modeling. HE and Masson staining revealed that the number of glands in the hUCB-MSC transplantation group was increased compared with that in IUA group (17.33±2.52 vs 4.33±1.53, P <0.001), and the fibrosis rate decreased (69.55%±2.42% vs 41.55%±1.99%, P =0.001). Western blot analyses of fibrosis-related proteins (TGF-β1 and TIMP1) showed elevated levels of TGF-β1 (0.91±0.05) and TIMP1 (0.99±0.01) proteins in the IUA group compared to control group (0.61±0.04, 0.68±0.07) ( P =0.001, 0.015). The hUCB-MSC transplantation group exhibited reduced expression of TGF-β1 (0.69±0.04) and TIMP1 (0.62±0.08) proteins compared to the IUA group ( P =0.005, 0.014). Western Blot results related to the PI3K/AKT signaling pathway [phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-AKT)] showed that the expression of p-PI3K(1.05±0.05) and p-AKT(1.17±0.06) in the IUA group increased compared to the control group (0.78±0.03, 0.85±0.05) ( P =0.002, 0.002). The expression of p-PI3K (0.74±0.02) and p-AKT (0.93±0.04) proteins in the hUCB-MSC transplantation group decreased compared to the IUA group ( P =0.003, 0.005). Conclusion: hUCB-MSC can repair the damaged endometrium in rabbit intrauterine adhesion model by increasing the number of endometrial glands and improving its level of fibrosis.

Gas-phase PbMg n - ( n = 2-12) cluster structures were globally searched on their potential energy surfaces by means of the CALYPSO prediction software. Structural optimization and calculations of properties such as relative energy and electronic structure were then carried out by density functional theory for each size of low energy isomer. The structural, relative stability, natural charge population, natural electronic configuration and distribution of the strongest peaks of the infrared and Raman spectra of the low energy isomers of PbMg n - ( n = 2-12) clusters were systematically investigated in the present work. It was shown that the PbMg 7 - cluster ground state isomer exhibits the highest stability, for which special electronic excitation and chemical bonding analyses were performed. It is reasonable to believe that this work enriches the structural, spectroscopic and other data of magnesium-based clusters and provides some theoretical basis for possible future experimental syntheses., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

Endothelial senescence, aging-related inflammation, and mitochondrial dysfunction are prominent features of vascular aging and contribute to the development of aging-associated vascular disease. Accumulating evidence indicates that DNA damage occurs in aging vascular cells, especially in endothelial cells (ECs). However, the mechanism of EC senescence has not been completely elucidated, and so far, there is no specific drug in the clinic to treat EC senescence and vascular aging. Here we show that various aging stimuli induce nuclear DNA and mitochondrial damage in ECs, thus facilitating the release of cytoplasmic free DNA (cfDNA), which activates the DNA-sensing adapter protein STING. STING activation led to a senescence-associated secretory phenotype (SASP), thereby releasing pro-aging cytokines and cfDNA to further exacerbate mitochondrial damage and EC senescence, thus forming a vicious circle, all of which can be suppressed by STING knockdown or inhibition. Using next-generation RNA sequencing, we demonstrate that STING activation stimulates, whereas STING inhibition disrupts pathways associated with cell senescence and SASP. In vivo studies unravel that endothelial-specific Sting deficiency alleviates aging-related endothelial inflammation and mitochondrial dysfunction and prevents the development of atherosclerosis in mice. By screening FDA-approved vasoprotective drugs, we identified Cilostazol as a new STING inhibitor that attenuates aging-related endothelial inflammation both in vitro and in vivo. We demonstrated that Cilostazol significantly inhibited STING translocation from the ER to the Golgi apparatus during STING activation by targeting S162 and S243 residues of STING. These results disclose the deleterious effects of a cfDNA-STING-SASP-cfDNA vicious circle on EC senescence and atherogenesis and suggest that the STING pathway is a promising therapeutic target for vascular aging-related diseases. A proposed model illustrates the central role of STING in mediating a vicious circle of cfDNA-STING-SASP-cfDNA to aggravate age-related endothelial inflammation and mitochondrial damage., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

The Lysosomal Protein Transmembrane 5 (LAPTM5) is a lysosomal transmembrane protein preferentially expressed in hematopoietic cells. The human LAPTM5 gene is located at position 1p34 and extends approximately 25 kb. Its protein includes five transmembrane domains, three PY motifs, and one UIM. The PY and UIM motifs can interact with various substrates, mediating sorting of proteins from Golgi to lysosome and subsequently participating in intracellular substrate transport and lysosomal stability regulation. Overexpression of LAPTM5 can induce lysosomal cell death (LCD), although the integrity of LAPTM5 protein is necessary for maintaining lysosome stability. Furthermore, LAPTM5 plays a role in autophagy activation during disease processes and has been confirmed to be closely associated with the regulation of immunity and inflammation. Therefore, LAPTM5 regulates a wide range of physiological processes and is involved in various diseases. This article summarizes the characteristics of the LAPTM5 gene and protein structure and provides a comprehensive review of the mechanisms involved in cell death, autophagy, immunity, and inflammation regulation. It emphasizes the significance of LAPTM5 in the clinical prevention and treatment of cardiovascular diseases, immune system disorders, viral infections, cancer, and other diseases, which could provide new therapeutic ideas and targets for human diseases., Competing Interests: Declaration of Competing Interest The authors declare no competing interests, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Extracellular vesicles (EVs) are being considered as a potential therapeutic option for ulcerative colitis (UC), and numerous preclinical studies have been conducted on the use of EVs for UC., Methods: A systematic review was conducted to compare the therapeutic effects of mammalian EVs and placebo on UC in animal models, along with a meta-analysis comparing naïve (unmodified) EVs and placebo. The search was performed in four databases (PubMed, Web of Science, Scopus, and EMBASE) up to September 13th, 2023. The primary outcomes included disease activity index (DAI), colonic mucosal damage index (CMDI), and adverse effects (PROSPERO ID: CRD42023458039)., Results: A total of 69 studies were included based on pre-determined criteria, involving 1271 animals. Of these studies, 51 measured DAI scores, with 98 % reporting that EVs could reduce DAI scores. Additionally, 5 studies reported CMDI and all showed that EVs could significantly reduce CMDI. However, only 3 studies assessed adverse effects and none reported any significant adverse effects. The meta-analysis of these studies (40 studies involving 1065 animals) revealed that naïve EVs could significantly decrease the DAI score (SMD = -3.00; 95 % CI: -3.52 to -2.48) and CMDI (SMD = -2.10; 95 % CI: -2.85 to -1.35)., Conclusion: The results indicate that mammalian EVs have demonstrated therapeutic benefits in animal models of UC; however, the safety profile of EVs remains inadequate which highlights the need for further research on safety outcomes., 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.)

Cisplatin is a widely used drug for the clinical treatment of tumors. However, nephrotoxicity limits its widespread use. A series of compounds including eight analogs ( G3-G10 ) and 40 simplifiers ( G11-G50 ) were synthesized based on the total synthesis of Psiguamer A and B, which were novel meroterpenoids with unusual skeletons from the leaves of Psidium guajava . Among these compounds, ( d )-G8 showed the strongest protective effect on cisplatin-induced acute kidney injury (AKI) in vitro and vivo , and slightly enhanced the antitumor efficacy of cisplatin. A mechanistic study showed that ( d )-G8 promoted the efflux of cisplatin via upregulating the copper transporting efflux proteins ATP7A and ATP7B. It enhanced autophagy through the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. ( d )-G8 showed no acute toxicity or apparent pathological damage in the healthy mice at a single dose of 1 g/kg. This study provides a promising lead against cisplatin-induced AKI.

Low-dimension metal halide perovskites are attractive for bandgap tunable optoelectronic materials. Among them, 1-D CsPbBr 3 quantum wires (QWs) are emerging as promising deep-blue luminescent material. However, the growth dynamics of 1-D perovskite QWs are intricate, making the study and control of 1-D QWs highly challenging. In this study, a strategy for controlling both the length and width of the CsPbBr 3 QWs was realized. The temperature-dependent isotropic growth mechanism was revealed and employed as the main tool for the oriented growth of 1-D CsPbBr 3 QWs for various aspect ratios. Our results pave the way for the controlled synthesis of ultrasmall perovskite nanocrystals.

Background: Sotos syndrome is an autosomal dominant disorder, whereas attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition. This report aimed to summarize the clinical and genetic features of a pediatric case of Soros syndrome and ADHD in a child exhibiting precocious puberty., Case Summary: The patient presented with accelerated growth and advanced skeletal maturation; however, she lacked any distinct facial characteristics related to specific genetic disorders. Genetic analyses revealed a paternally inherited heterozygous synonymous mutation [c.4605C>T (p.Arg1535Arg)]. Functional analyses suggested that this mutation may disrupt splicing, and bioinformatics analyses predicted that this mutation was likely pathogenic. After an initial diagnosis of Sotos syndrome, the patient was diagnosed with ADHD during the follow-up period at the age of 8 years and 7 months., Conclusion: The potential for comorbid ADHD in Sotos syndrome patients should be considered to avoid the risk of a missed diagnosis., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To explore the related factors of thrombocytopenia (TCP) occurrence in patients with cirrhosis. Methods: A cross-sectional study was conducted. Inpatients with an initial diagnosis of cirrhosis at Peking University First Hospital from January 1, 2010 to December 31, 2020 were included. Clinical data such as demographic characteristics, etiology of cirrhosis, complications of cirrhosis, laboratory indicators, Child-Pugh grade, invasive procedures, and mortality during hospitalization were collected. A logistic regression model was used to explore the related factors of TCP occurrence in patients with cirrhosis. Categorical variables were compared by the χ (2) test. The inter-group comparison was performed using continuous variables, a t -test, one-way analysis of variance (ANOVA), or a nonparametric test. Results: There were a total of 2 592 cases of cirrhosis. 75 cases with incomplete clinical data were excluded. 2 517 cases were included for analysis. The median age was 58 (50, 67) years. Males accounted for 64%. 1 435 cases (57.0%) developed TCP, and 434 cases (17.2%) had grade 3-4 TCP. Gender, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and concomitant esophagogastric varices (EGV) were the major factors associated with TCP. Females were more prone to combine with TCP ( OR =1.32, 95% CI : 1.12-1.56, P =0.001). Patients combined with EGV ( OR =3.09, 95% CI : 2.63-3.65, P <0.001) were more prone to develop TCP, which was associated with the increased incidence of hypersplenism ( P <0.001). Patients with PBC ( OR =0.64, 95% CI : 0.50-0.82, P <0.001) and PSC ( OR =0.23, 95% CI : 0.06-0.65, P =0.010) were less prone to develop TCP, which was due to the shorter prothrombin time and better coagulation function of PBC patients ( P <0.001), and the lower proportion of hypersplenism in combined PSC patients ( P =0.004). Patients with TCP and grade 3-4 TCP had a higher rate of hemostatic procedures ( P <0.05), but a lower rate of liver biopsy ( P <0.05). Patients with grade 3-4 TCP had a higher nosocomial mortality rate compared to those without ( P =0.004). Conclusion: TCP is common in patients with cirrhosis. However, TCP occurrence is higher in female patients with EGV and lower in patients combined with PBC and PSC. TCP affects invasive procedures and is associated with adverse outcomes.

The etiology and pathophysiology of heart failure are still unknown. Increasing evidence suggests that abnormal microRNAs (miRNAs) and transcription factors (TFs) expression may be associated with the development of heart failure. Therefore, this study aims to explore key miRNAs, TFs, and related genes in heart failure to gain a greater understanding of the pathogenesis of heart failure. To search and download the dataset of mRNA chips related to heart failure from the GEO database (GSE59867, GSE9128, and GSE134766), we analyzed differential genes and screened the common differentially expressed genes on two chips using R language software. The binary interactions and circuits among miRNAs, TFs, and corresponding genes were determined by Pearson correlation coefficient. A regulatory network of miRNAs, TFs, and target genes was constructed based on bioinformatics. By comparing the sequences of patients with and without heart failure, five downregulated genes with hypermethylated mRNA and three upregulated genes with hypomethylated mRNA were identified. The miRNA-TF gene regulatory network consisted of 26 miRNAs, 22 TFs and six genes. GO and KEGG analysis results revealed that BP terms like cellular response to organic substance, cellular response to cytokine stimulus, and KEGG pathways like osteoclast differentiation, MAPK signaling pathway, and legionellosis were enriched of the DEGs. TMEM87A, PPP2R2A, DUSP1, and miR-92a have great potential as biomarkers for heart failure. The integrated analysis of the mRNA expression spectrum and microRNA-transcription factor-gene revealed the regulatory network of heart failure, which may provide clues to its alternative treatment., (© 2024. The Author(s).)

How plants find a way to thrive in alpine habitats remains largely unknown. Here we present a chromosome-level genome assembly for an alpine medicinal herb, Triplostegia glandulifera (Caprifoliaceae), and 13 transcriptomes from other species of Dipsacales. We detected a whole-genome duplication event in T. glandulifera that occurred prior to the diversification of Dipsacales. Preferential gene retention after whole-genome duplication was found to contribute to increasing cold-related genes in T. glandulifera . A series of genes putatively associated with alpine adaptation (e.g. CBF s, ERF-VII s, and RAD51C ) exhibited higher expression levels in T. glandulifera than in its low-elevation relative, Lonicera japonica . Comparative genomic analysis among five pairs of high- vs low-elevation species, including a comparison of T. glandulifera and L. japonica , indicated that the gene families related to disease resistance experienced a significantly convergent contraction in alpine plants compared with their lowland relatives. The reduction in gene repertory size was largely concentrated in clades of genes for pathogen recognition (e.g. CNL s, prRLP s, and XII RLK s), while the clades for signal transduction and development remained nearly unchanged. This finding reflects an energy-saving strategy for survival in hostile alpine areas, where there is a tradeoff with less challenge from pathogens and limited resources for growth. We also identified candidate genes for alpine adaptation (e.g. RAD1 , DMC1 , and MSH3 ) that were under convergent positive selection or that exhibited a convergent acceleration in evolutionary rate in the investigated alpine plants. Overall, our study provides novel insights into the high-elevation adaptation strategies of this and other alpine plants., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

MXene, renowned for its natural "quantum-confined-superfluidic" (QSF) channels, demonstrates superior electrical/thermal conductivity, favorable hydrophilicity, and remarkable mechanical strength, rendering it an ideal candidate for multiresponsive actuators, which are promising for soft electronics and robots. Currently, most MXene-based actuators are mainly prepared by combining an active layer and an inner layer, with only a few utilizing regulated QSF channels. However, tailoring QSF channels for multiresponsive actuators is extremely challenging. Herein, we introduce a multiresponsive graphene oxide (GO)&Fe 3 O 4 /MXene actuator that can respond to humidity, light, heat, electricity, and magnetic fields by constructing asymmetric QSF channels. The asymmetric water adsorption, transportation, and desorption behaviors, controlled by the different QSF channels between the GO&Fe 3 O 4 layer and the MXene layer, enable the multiresponsiveness of the actuator. As proof-of-concept demonstrations, several smart devices, such as a bionic crab-like crawler, a transporting flower robot, and a smart gripper, are prepared, holding great potential for advancing future soft robotics.

Objective: To analyze the transfusion effect of different platelet matching schemes in patients with platelet transfusion refractoriness (PTR). Methods: A total of 94 patients with PTR received by Taiyuan Blood Center from January to December 2021 were retrospectively analyzed, including 26 males and 68 females, aged 53(34,66) years. Platelet antibody screening was performed by enzyme-linked immunosorbent assay (ELISA). For patients with positive human leukocyte antigen (HLA) class Ⅰ antibodies, Luminex platform liquid chip assay was used to identify the specificity of antibodies, and platelets with missing allelic expression antigen corresponding to their specific antibodies were found in the platelet donor gene database established in our laboratory. For patients with negative class HLA-Ⅰ antibody screening, medium and high-resolution HLA-A and B alleles were genotyped by polymerase chain reaction restriction sequence specific oligonucleotide (PCR-SSO), and the compatible platelets were searched from the platelet donor gene database by HLA cross-reactive group genotype matching scheme or directly selected by serological cross-matching. The PCI compliance rate and total transfusion effective rate of different mismatch site groups and different matching scheme groups were statistically analyzed. Results: Platelet antibody was detected in 39 of 94 PTR patients with a positive rate of 41.5%, and all of them were HLA-Ⅰ antibodies, and 1 case was accompanied by human platelet antigen (HPA) antibody. A total of 134 times of compatible platelets were supplied to 39 patients with HLA-Ⅰ antibody positive by using antibody avoidance matching method. And the total effective rate of transfusion was 97.8% (131/134); The PCI compliance rates of HLA-A antigen mismatch, HLA-B antigen mismatch and HLA-A and B antigen mismatch groups were 81.6% (31/38), 86.5% (32/37) and 78.6% (22/28), respectively. The total effective rate of transfusion was 97.4% (37/38), 94.6% (35/37) and 100% (28/28), respectively, with no statistical significance (all P >0.05). A total of 118 times of compatible platelets were provided by HLA antigen cross-reaction group genotype matching and serological cross-matching, 90 transfusion effects were collected during follow-up, and the total effective rate was 76.7% (69/90). Conclusion: The combination of different platelet matching schemes can improve the PCI compliance rate and the total effective rate of transfusion in PTR patients.

In rice-vegetable rotation systems in tropical areas, a large amount of nitrate nitrogen accumulates after fertilization in the melon and vegetable season, which leads to the leaching of nitrate nitrogen and a large amount of N 2 O emission after the seasonal flooding of rice, which leads to nitrogen loss and intensification of the greenhouse effect. How to improve the utilization rate of nitrate nitrogen and reduce N 2 O emissions has become an urgent problem to be solved. Six treatments were set up [200 mg·kg -1 KNO 3 (CK); 200 mg·kg -1 KNO 3 + 2% biochar addition (B); 200 mg·kg -1 KNO 3 +1% peanut straw addition (P); 200 mg·kg -1 KNO 3 + 2% biochar + 1% peanut straw addition (P+B); 200 mg·kg -1 KNO 3 + 1% rice straw addition (R); 200 mg·kg -1 KNO 3 + 2% biochar+1% rice straw addition (R+B)] and cultured at 25℃ for 114 d to explore the effects of organic material addition on greenhouse gas emissions and nitrogen use after flooding in high nitrate nitrogen soil. The results showed that compared with that in CK, adding straw or combining straw with biochar significantly increased soil pH ( P <0.05). The B and P treatments significantly increased the cumulative N 2 O emissions by 41.6% and 28.5% ( P <0.05), and the P+B, R, and R+B treatments significantly decreased the cumulative N 2 O emissions by 14.1%, 24.7%, and 36.7% ( P <0.05), respectively. The addition of straw increased the net warming potential of greenhouse gases (NGWP). The addition of coir biochar significantly reduced the effect of straw on NGWP ( P <0.05). The combined application of straw and biochar decreased NGWP, and P+B significantly decreased NGWP, but that with R+B was not significant ( P >0.05). Adding straw or biochar significantly increased soil microbial biomass carbon (MBC) ( P <0.05), and that of P+B was the highest (502.26 mg·kg -1 ). The combined application of straw and biochar increased soil microbial biomass nitrogen (MBN), and that of P+B was the highest. The N 2 O emission flux was negatively correlated with pH ( P <0.01) and positively correlated with NH 4 + -N and NO 3 - -N ( P <0.01). The cumulative emission of N 2 O was negatively correlated with MBN ( P <0.05). There was a significant negative correlation between NO 3 - -N and MBN ( P <0.01), indicating that the reduction in NO 3 - -N was likely to be held by microorganisms, and the increase in the microbial hold of NO 3 - -N also reduced N 2 O emission. In conclusion, the combined application of peanut straw and coconut shell biochar could significantly inhibit N 2 O emission and increase soil MBC and MBN, which is a reasonable measure to make full use of nitrogen fertilizer, reduce nitrogen loss, and slow down N 2 O emission after the season of Hainan vegetables.

Objectives: Cerebral small vessel disease is a group of pathologies in which alterations of the brain's blood vessels contribute to stroke and neurocognitive changes. Recently, a neurotoxic waste clearance system composed of perivascular spaces abutting the brain's blood vessels, termed the glymphatic system, has been identified as a key player in brain homeostasis. Given that small vessel disease and the glymphatic system share anatomical structures, this review aims to reexamine small vessel disease in the context of the glymphatic system and highlight novel aspects of small vessel disease physiology., Materials and Methods: This review was conducted with an emphasis on studies that examined aspects of small vessel disease and on works characterizing the glymphatic system. We searched PubMed for relevant articles using the following keywords: glymphatics, cerebral small vessel disease, arterial pulsatility, hypertension, blood-brain barrier, endothelial dysfunction, stroke, diabetes., Results: Cerebral small vessel disease and glymphatic dysfunction are anatomically connected and significant risk factors are shared between the two. These include hypertension, type 2 diabetes, advanced age, poor sleep, obesity, and neuroinflammation. There is clear evidence that CSVD hinders the effective functioning of glymphatic system., Conclusion: These shared risk factors, as well as the model of cerebral amyloid angiopathy pathogenesis, hint at the possibility that glymphatic dysfunction could independently contribute to the pathogenesis of cerebral small vessel disease. However, the current evidence supports a model of cascading dysfunction, wherein concurrent small vessel and glymphatic injury hinder glymphatic-mediated recovery and promote the progression of subclinical to clinical disease., Competing Interests: Declaration of competing interest James R. Brorson is supported by National Institutes of Health grants R01AG06263 (Aggarwal) and R61NS135583 (Brorson), and has provided medical-legal consultation and consultation to the National Peer Review Corporation., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: The DYNC1H1 variants are associated with abnormal brain morphology and neuromuscular disorders that are accompanied by epilepsy. This study aimed to explore the relationship between DYNC1H1 variants and epilepsy., Materials and Methods: Trios-based whole-exome sequencing was performed on patients with epilepsy. Previously reported epilepsy-related DYNC1H1 variants were systematically reviewed to analyse genotype-phenotype correlation., Results: The DYNC1H1 variants were identified in four unrelated cases of infant-onset epilepsy, including two de novo and two biallelic variants. Two patients harbouring de novo missense variants located in the stem and stalk domains presented with refractory epilepsies, whereas two patients harbouring biallelic variants located in the regions between functional domains had mild epilepsy with infrequent focal seizures and favourable outcomes. One patient presented with pachygyria and neurodevelopmental abnormalities, and the other three patients presented with normal development. These variants have no or low frequencies in the Genome Aggregation Database. All the missense variants were predicted to be damaging using silico tools. Previously reported epilepsy-related variants were monoallelic variants, mainly de novo missense variants, and all the patients presented with severe epileptic phenotypes or developmental delay and malformations of cortical development. Epilepsy-related variants were clustered in the dimerization and stalk domains, and generalized epilepsy-associated variants were distributed in the stem domain., Conclusion: This study suggested that DYNC1H1 variants are potentially associated with infant-onset epilepsy without neurodevelopmental disorders, expanding the phenotypic spectrum of DYNC1H1. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic variation., Competing Interests: Declaration of Competing Interest The authors have stated that they had no interests which might be perceived as posing a conflict or bias., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Six pairs of enantiomeric dilignans, (+)/(-)-magdiligols A-F, have been isolated from an ethanolic extract of the barks of Magnolia officinalis var. biloba. Their chemical structures were elucidated by extensive spectroscopic analyses, NMR calculation with DP4+ analysis, and the electronic circular dichroism spectra calculation. (+)/(-)-1-3 possessed a dihydrobenzopyran ring, while a propyl chain of 1 was linked via ether bond. (+)/(-)-Magdiligols D and E ((+)/(-)-4 and 5) were dilignans possessing a furan ring. (+)-Magdiligol B ((+)/(-)-2), (+)/(-)-magdiligol C ((+)/(-)-3), and racemes 2, 3, and 5 showed potential hepatoprotective effects against APAP-induced HepG2 cell damage, increased the cell viability from 65.4% to 72.7, 78.7.76.6, 73.9, 77.9 and 73.2%, via decreasing the level of the live enzymes ALH and LDH consistently. (+)/(-)-Magdiligols B-D ((+)/(-)-2-4) and (+)/(-)-magdiligol F ((+)/(-)-6) exhibited significant antioxidative activity. (+)/(-)-Magdiligols B-C ((+)/(-)-2 and 3), (-)-magdiligol D ((-)-4), and (+)-magdiligol E ((+)-5) displayed significant PTP1B inhibitory activity with IC 50 values 1.41-3.42 μM. (+)/(-)-Magdiligol B ((+)/(-)-2), and its raceme (2) demonstrated α-glucosidase inhibitory activity with the IC 50 values 1.47, 2.88 and 1.85 μM, respectively., 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 Ltd. All rights reserved.)

Purpose: ATP6V1A variants have been identified in patients with highly variable phenotypes such as autosomal dominant epileptic encephalopathy and autosomal recessive cutis laxa. However, the mechanism underlying phenotype variation is unknown. We screened ATP6V1A variants in patients with epilepsy and analyzed the genotype-phenotype correlation to explain the mechanism underlying phenotypic variations., Methods: We performed trio-based whole-exome sequencing in people with epilepsy without acquired causes. All previously reported ATP6V1A variants were systematically retrieved from the HGMD and PubMed databases., Results: Three novel de novo ATP6V1A variants, including c.749G>C/p.Gly250Ala, c.782A>G/p.Gln261Arg, and c.1103T>C/p.Met368Thr, were identified in three unrelated cases with childhood focal (partial) epilepsy. None of the variants were listed in any public population database and evaluated as likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics (ACMG). All persons showed good responses to anti-seizure medication and psychomotor development was normal. Further analysis showed that monoallelic missense variants were associated with epilepsy with variable severity, whereas biallelic variants resulted in developmental abnormalities of multisystem that may result in early lethality., Conclusion: Childhood focal epilepsy with favorable outcome was probably a novel phenotype of ATP6V1A. ATP6V1A variants are associated with a range of phenotypes that correlate with genotypes. The relationship between phenotype severity and the genotype (genetic impairment) of ATP6V1A variants helps explain the phenotypic variations., 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 © 2023. Published by Elsevier Ltd.)

In order to study the safe utilization of acid cadmium （Cd） contaminated soil， light and moderate Cd-contaminated farmland in Shangluo， Shaanxi Province was taken as the research object， and lime， biochar， and calcium magnesium phosphate fertilizer were applied. Through the wheat-maize rotation experiment， the safe utilization effect of different amounts of passivator on Cd-contaminated soil was explored， and the best ratio of passivator was selected. The results showed that： ① the soil quality could be improved to varying degrees by applying the passivator. ② After the application of amendments， the grain yield of wheat and maize increased to different degrees. ③ The lime 2 340 kg·hm -2 （C3） treatment had the best effect， which increased the soil pH of wheat and corn by 1.453 and 1.717 units， respectively， and reduced the available Cd content by 34.38% and 30.20%， respectively. ④ The application of biochar 1 800 kg·hm -2 （B2） treatment had the best effect on reducing the Cd contents in wheat roots， straws， and grains， which were significantly reduced by 53.60%， 38.86%， and 52.96%， respectively， compared with that in CK. The Cd content in wheat grains was reduced to 0.09 mg·kg -1 ， which was lower than the limit value of wheat Cd （0.1 mg·kg -1 ） specified in the "National food safety standard food pollutant limit" （GB 2762-2017）. The application of the biochar 1 260 kg·hm -2 （B1） treatment had the best comprehensive effect on reducing the Cd contents of maize roots， straws， and grains， which were significantly reduced by 43.74%， 53.20%， and 94.57%， respectively， compared with that in CK. The Cd content of maize grains was reduced to 0.001 9 mg·kg -1 ， which was far lower than the limit value of maize Cd （0.1 mg·kg -1 ） specified in the "National food safety standard food pollutant limit" （GB 2762-2017）. Therefore， under the conditions of the field experiment， considering the influence of various indexes， biochar had the best effect on farmland soil in the wheat-maize rotation area with mild to moderate Cd pollution.

Background: The GABRA1 gene, encoding the GABR A R subunit α1, plays vital roles in inhibitory neurons. Previously, the GABRA1 gene has been identified to be associated with developmental and epileptic encephalopathy (DEE) and idiopathic generalized epilepsy (IGE). This study aims to explore the phenotypic spectrum of GABRA1 and molecular subregional effect analysis., Methods: Trios-based whole-exome sequencing was performed in patients with epilepsy. Previously reported GABRA1 mutations were systematically reviewed to analyze the molecular subregional effects., Results: De novo GABRA1 mutations were identified in six unrelated patients with heterogeneous epilepsy, including three missense mutations (p.His83Asn, p.Val207Phe, and p.Arg214Cys) and one frameshift mutation (p.Thr453Hisfs*47). The two missense mutations, p.His83Asn and p.Val207Phe, were predicted to decrease the protein stability but no hydrogen bond alteration, with which the two patients also presented with mild genetic epilepsy with febrile seizures plus and achieved seizure-free status by monotherapy. The missense variant p.Arg214Cys was predicted to decrease protein stability and destroy hydrogen bonds with surrounding residues, which was recurrently identified in three cases with severe DEE. The frameshift variant p.Thr453Hisfs*47 was located in the last fifth residue of the C-terminus and caused an extension of 47 amino acids, with which the patients presented with moderated epilepsy with generalized tonic-clonic seizures alone (GTCA) but achieved seizure-free status by four drugs. The four variants were not presented in gnomAD and were evaluated as "pathogenic/likely pathogenic" according to ACMG criteria. Analysis of all reported cases indicated that patients with mutations in the N-terminal extracellular region presented a significantly higher percentage of FS and DEE, and the patients with variants in the transmembrane region presented earlier seizure onset ages., Significance: This study suggested that GABRA1 variants were potentially associated with a spectrum of epilepsies, including EFS+, DEE, and GTCA. Phenotypic severity may be associated with the damaging effect of variants. The molecular subregional effects help in understanding the underlying mechanism of phenotypic variation., 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 Liu, Luo, Zhang, Lin, Lan, Li, Shi, Su, Yi, Zhou and Li.)

Background: Accompanying islet α- and β-cell dysregulation in type 2 diabetes (T2D) at the microscopic scale, alterations in body composition at the macroscopic scale may affect the pathogenesis of T2D. However, the connections between body composition and islet α-cell and β-cell functions in T2D have not been thoroughly explored., Methods: For this cross-sectional study, we recruited a total of 729 Chinese Han patients with T2D in a consecutive manner. Dual-energy X-ray absorptiometry (DXA) was used to measure body composition, which included total bone-free mass, total fat and lean mass, trunk fat and lean mass and limb fat and lean mass. Every patient underwent an oral glucose tolerance test to simultaneously detect glucose, C-peptide and glucagon. The indices of islet α-cell function included fasting glucagon levels and the area under the curve of glucagon after a challenge (AUC glucagon ), while the indices of β-cell function included the insulin sensitivity index derived from C-peptide (ISI C-peptide ) and the area under the curve of C-peptide after a challenge (AUC C-peptide )., Results: Among all patients, fat mass, especially trunk fat mass, was significantly correlated with ISI C-peptide and AUC C-peptide levels (r = - 0.330 and 0.317, respectively, p < 0.001), while lean mass, especially limb lean mass, was significantly correlated with fasting glucagon and AUC glucagon levels (r = - 0.196 and - 0.214, respectively, p < 0.001). Moreover, after adjusting for other relevant variables via multivariate linear regression analysis, increased trunk fat mass was independently associated with decreased ISI C-peptide (β = - 0.247, t = - 3.628, p < 0.001, partial R 2  = 10.9%) and increased AUC C-peptide (β = 0.229, t = 3.581, p < 0.001, partial R 2  = 8.2%), while decreased limb lean mass was independently associated with increased fasting glucagon (β = - 0.226, t = - 2.127, p = 0.034, partial R 2  = 3.8%) and increased AUC glucagon (β = - 0.218, t = - 2.050, p = 0.041, partial R 2  = 2.3%). Additionally, when separate analyses were performed with the same concept for both sexes, we found that increased trunk fat mass was still independently associated with decreased ISI C-peptide and increased AUC C-peptide , while decreased limb lean mass was still independently associated with increased fasting glucagon and AUC glucagon ., Conclusions: Increased trunk fat mass may partly account for decreased insulin sensitivity and increased insulin secretion, while decreased limb lean mass may be connected to increased fasting glucagon and postprandial glucagon secretion., (© 2024. The Author(s).)

Three new monoterpene phenol dimers, bisbakuchiols V-X ( 1-3 ), and two bakuchiol ethers ( 4 and 5 ), along with four known compounds ( 6 - 9 ) were isolated from the fruits of Psoralea corylifolia . Their structures were elucidated based on extensive spectral analysis. The absolute configurations of 1 , 2 , 4 , and 5 were specified by quantum chemical calculations of ECD spectra.

Three novel Co-based coordination polymers including {[Co(L)(μ 3 -O) 1/3 ] 2 } n (1), {[Co(L)(bimb)]} n (2) and {[Co(L)(bimmb) 1/2 ]} n (3) (H 2 L = 2,6-di(4-carboxylphenyl)-4-(4-(triazol-1-ylphenyl))pyridine), bimb = 1,4-bis(lmidazol) butane, bimmb = 1,4-bis(imidazole-1-ylmethyl)benzene) were successfully prepared under solvothermal conditions and characterized. Single-crystal X-ray diffraction analyses revealed that 1 possesses a 3D architecture composed of a trinuclear cluster [Co 3 N 3 (CO 2 ) 6 (μ 3 -O)], 2 exhibits a 2D new topological framework with the point symbol (8 4 ·12 2 )(8) 2 , whereas 3 shows a unique six-fold interpenetrated 3D framework with a (6 3 ·8 2 ·10) 2 (6 3 ) 2 (8) topology. Impressively, all of them can function as a highly selective and sensitive fluorescent sensor for the biomarker methylmalonic acid (MMA) via fluorescence quenching. The low detection limit, reusability and high anti-interference performance together make 1-3 become promising sensors for the practical detection of MMA. Furthermore, the successful application of MMA detection in urine sample was demonstrated, which may be a potential candidate for the further development of clinical diagnostic tools., Competing Interests: Declaration of competing interest There is no competing interest declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the performance of coronary computed tomography angiography (CCTA) derived characteristics including CT derived fractional flow reserve (CT-FFR) with FFR as a reference standard in identifying the lesion-specific ischemia by machine learning (ML) algorithms., Methods: The retrospective analysis enrolled 596 vessels in 462 patients (mean age, 61 years ± 11 [SD]; 71.4 % men) with suspected coronary artery disease who underwent CCTA and invasive FFR. The data were divided into training cohort, internal validation cohort, external validation cohorts 1 and 2 according to participating centers. All CCTA-derived parameters, which contained 10 qualitative and 33 quantitative plaque parameters, were collected to establish ML model. The Boruta and unsupervised clustering algorithm were implemented to select important and non-redundant parameters. Finally, the eight features with the highest mean importance were included for further ML model establishment and decision tree building. Five models were built to predict lesion-specific ischemia: stenosis degree from CCTA, CT-FFR, ΔCT-FFR, ML model and nested model., Results: Low-attenuation plaque, bend and lesion length were the main predictors of ischemia-specific lesions. Of 5 models, the ML model showed favorable discrimination for ischemia-specific lesions in the training and three validation sets (area under the curve [95 % confidence interval], 0.93 [0.90-0.96], 0.86 [0.79-0.94], 0.88 [0.83-0.94], and 0.90 [0.84-0.96], respectively). The nested model which combined the ML model and CT-FFR showed better diagnostic efficacy (AUC [95 %CI], 0.96 [0.94-0.99], 0.92 [0.86-0.99], 0.92 [0.86-0.99] and 0.94 [0.91-0.98], respectively; all P < 0.05), and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were significantly higher than CT-FFR alone., Conclusions: Comprehensive CCTA-derived multiparameter model could better predict the ischemia-specific lesions by ML algorithms compared to stenosis degree from CTA, CT-FFR and ΔCT-FFR. Decision tree can be used to predict myocardial ischemia effectively., 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. This work was supported by the Jiangsu Province Key Project of Comprehensive Prevention and Control of Chronic Diseases (grant BE2020699)., (Copyright © 2023. Published by Elsevier B.V.)

Background: Inflammation-related NLRP3/Caspase-1/GSDMD-mediated pyroptosis is involved in the progression of ulcerative colitis (UC). β-sitosterol (SIT) was reported to have anti-inflammatory effects on experimental colitis, while the regulation of SIT on pyroptosis is unclear. Therefore, the present study aimed to define the protective and healing effects of SIT on dextran sulfate sodium (DSS)-induced experimental UC rats and human epithelial colorectal adenocarcinoma cells (Caco-2) and explore the underlying mechanisms that are responsible for its effects on NLRP3/Caspase-1/GSDMD-mediated pyroptosis in UC. Methods: UC model rats were established by oral 4% DSS. Following colitis injury, the animals received SIT (doses of 50, 100, and 200 mg/kg) treatment for 2 weeks. For in vitro study, we exposed Caco-2-50 mg/mL DSS with or without SIT (concentrations of 8 and 16 μg/mL). Disease activity index (DAI) and histopathological injury were assessed in vivo . Activation proteins of nuclear factor kappa B (NF-κB) signaling axis, and tight junction-related proteins of zonula occludens-1 (ZO-1) and occludin were detected in colon tissues. TNF-α, IL-1β, and IL-18 in serum and cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Changes in NLRP3/Caspase-1/GSDMD-mediated pyroptosis signaling pathway activation were analyzed both in tissues and cells. Results: Our findings suggested that SIT treatment attenuated the severity of 4% DSS-induced UC by protecting rats from weight and colon length loss, and macroscopic damage. SIT also reduced proinflammatory factors production (TNF-α, IL-1β, and IL-18) in serum and cell supernatant. Mechanistically, SIT downregulated the expression levels of pyroptosis-related proteins including Caspase-1, cleaved-Caspase-1, NLRP3, GSDMD, and GSDMD-N in colon tissues and Caco-2 cells. Further analysis indicated that SIT maintained the colonic barrier integrity by enhancing the protein expression of ZO-1 and occludin. Conclusion: We confirmed that SIT exerts protective and therapeutic effects on DSS-induced colitis injury by suppressing NLRP3/Caspase-1/GSDMD-mediated pyroptosis and inflammation response. These findings demonstrated that SIT could be a potential medication for UC treatment., 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 Zhang, Ge, Ji, Li, Zhang, Wang, Zhang, Zhang and Chen.)

Background: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people., Methods: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively., Results: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (β = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; β = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (β = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women., Conclusions: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The evidence about the effect of non-essential metal mixture on fasting plasma glucose (FPG) levels among older adults without diabetes is limited. This study aims to estimate the individual and joint relationship between five non-essential metals and FPG levels in Chinese older adults without diabetes. This study included 2362 older adults without diabetes. Urinary concentrations of five non-essential metals, i.e., cesium (Cs), aluminum (Al), thallium (Tl), cadmium (Cd), and arsenic (As), were detected by inductively coupled plasma mass spectrometry (ICP-MS). The associations of single metals and the metal mixture with FPG levels were assessed using linear regression and Bayesian kernel machine regression (BKMR) models, respectively. Adjusted single-metal linear regression models showed positive associations of urinary Al (β = 0.016, 95%CI: 0.001-0.030) and Cs (β = 0.018, 95%CI: 0.006-0.031) with FPG levels. When comparing the 2th, 3th, and 4th quartiles of urine Cs to its 1th quartile, the significant associations between Cs and FPG levels were found and presented as an "inverted U" trend (β Q2 vs. Q1 : 0.034; β Q3 vs. Q1 :0.054; β Q4 vs. Q1 : 0.040; all P<0.05). BKMR analyses showed urinary level of Cs exhibited an "inverted U" shape association with FPG levels. Moreover, the FPG levels increased linearly with the raised levels of the non-essential metal mixture, and the posterior inclusion probability (PIP) of Cs was the highest (0.92). Potential positive interaction of As and Cs on FPG levels was found in BKMR model. Stratified analysis displayed significant interactions of hyperlipidemia and urine Cs or Tl on FPG levels. An inverse U-shaped association between Cs and FPG was found, individually and as mixture. The FPG levels increased with the raised levels of the non-essential metal mixture, and Cs was the most contributor to FPG levels. Further research is required to confirm the correlation between non-essential metals and FPG levels and to clarify the underlying mechanisms., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction and Objectives: Renal and bone impairment has been reported in chronic hepatitis B (CHB) patients receiving long-term tenofovir disoproxil fumarate (TDF) therapy. This study aimed to assess the incidence of renal and bone impairment in CHB patients with long-term TDF therapy and to identify the changes in bone mineral density (BMD) and renal function in these patients after switching to entecavir (ETV) or tenofovir alafenamide (TAF)., Materials and Methods: This retrospective study collected clinical data from CHB patients who received TDF monotherapy over 96 weeks. The changes in BMD and renal function were analyzed after 96 weeks of switching antiviral regimens (ETV or TAF) or maintenance TDF., Results: At baseline, 154 patients receiving TDF monotherapy over 96 weeks were enrolled, with a younger median age of 36.75 years, 35.1% (54/154) of patients experienced elevated urinary β2 microglobulin and 20.1% (31/154) of patients had reduced hip BMD (T<-1). At week 96, among the 123 patients with baseline normal BMD, patients who maintained TDF (n=85) had experienced a decrease in hip BMD, while patients who switched antiviral regimens (n=38) experienced an increase (-13.97% vs 2.34%, p<0.05). Among patients with a baseline reduced BMD (n=31), the alterations in BMD were similar in patients who maintained TDF (n=5) and those who switched antiviral regimens (n=26) (-15.81% vs 7.35%, p<0.05). Irrespective of baseline BMD status, renal function decreased significantly in patients who maintained TDF and improved in patients who switched antiviral regimens., Conclusions: Younger CHB patients on long-term TDF therapy are at high risk for bone and renal impairment, with the risk being reduced when switched to ETV or TAF., Competing Interests: Declaration of interests None., (Copyright © 2023 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: Acute liver failure (ALF) is characterized by severe liver dysfunction, rapid progression and high mortality and is difficult to treat. Studies have found that sulforaphane (SFN), a nuclear factor E2-related factor 2 (NRF2) agonist, has anti-inflammatory, antioxidant and anticancer effects, and has certain protective effects on neurodegenerative diseases, cancer and liver fibrosis. This paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of action., Methods: Lipopolysaccharide and D-galactosamine were used to induce liver injury in vitro and in vivo. NRF2 agonist SFN and histone deacetylase 6 (HDAC6) inhibitor ACY1215 were used to observe the protective effect and possible mechanisms of SFN in ALF, respectively. Cell viability, lactate dehydrogenase (LDH), Fe 2+ , glutathione (GSH) and malondialdehyde (MDA) were detected. The expression of HDAC6, NRF2, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) were detected by Western blotting and immunofluorescence., Results: Our results show that NRF2 was activated by SFN. LDH, Fe 2+ , MDA and ACSL4 were downregulated, while GSH, GPX4 and SLC7A11 were upregulated by SFN in vitro and in vivo, indicating the inhibitory effect of SFN on ferroptosis. Additionally, HDAC6 expression was decreased in the SFN group, indicating that SFN could downregulate the expression of HDAC6 in ALF. After using the HDAC6 inhibitor, ACY1215, SFN further reduced HDAC6 expression and inhibited ferroptosis, indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity., Conclusion: SFN has a protective effect on ALF, and the mechanism may include reduction of ferroptosis through the regulation of HDAC6. Please cite this article as: Zhang YQ, Shi CX, Zhang DM, Zhang LY, Wang LW, Gong ZJ. Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity. J Integr Med. 2023; 21(5): 464-473., 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 © 2023 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

Gene knockout is a technique routinely used in basic experimental research, particularly in mouse skeletal and developmental studies. Tamoxifen-induced Cre/loxp system is known for its temporal and spatial precision and commonly utilized by researchers. However, tamoxifen has been shown its side effects on affecting the phenotype of mouse bone directly. This review aimed to optimize tamoxifen administration regimens including its dosage and duration, to identify an optimal induction strategy that minimizes potential side effects while maintaining recombination efficacy. This study will help researchers in designing gene knockout experiments in bone when using tamoxifen., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interests., (Copyright © 2023. Published by Elsevier Masson SAS.)

Probiotics are widely used in aquaculture. This article aims to study the effect of Bacillus amyloliquefaciens LSG2-8 on the intestinal barrier function of Rhynchocypris lagowskii. B. amyloliquefaciens LSG2-8 were added to R. lagowskii basal diets (CK) as additives at four concentrations: 1.0 × 10 6 (D-6), 1.0 × 10 7 (D-7), 1.0 × 10 8 (D-8) and 1.0 × 10 9 (D-9) CFU g -1 by dry weight of basal diet. After a 56-day feeding experiment, the activities of intestinal digestive enzymes and immunity-related enzymes of R. lagowskii on group D-6, D-7, D-8 and D-9 diet were significantly higher than the control (P < 0.05). In molecular experiments, the authors found that the levels of TGF-β mRNA, IL-10 mRNA, ZO-1 mRNA and claudin-3 mRNA in group D-8 R. lagowskii were significantly higher (P < 0.05) than those of the control and other groups. Furthermore, the levels of IL-1β and IL-8 mRNA of R. lagowskii on group D-6, D-7, D-8 and D-9 diet were significantly lower than those of the control (P < 0.05). In addition, the authors found that B. amyloliquefaciens LSG2-8 can regulate the intestinal flora balance and improve the intestinal structure of R. lagowskii. In conclusion, B. amyloliquefaciens LSG2-8 can improve the intestinal barrier function of R. lagowskii and can be used as a feed additive in aquaculture., (© 2023 Fisheries Society of the British Isles.)

Objective: To explore the potential application value of animal model training in improving the comprehensive clinical ability of postgraduate students of dentistry and to provide reference for new methods of preclinical skills teaching., Methods: A total of 40 postgraduate students of dentistry were assigned to two groups, an experimental group and a control group. The control group took the routine teaching course on root canal treatment for the right mandibular first molar, using a simulated model of human head. The experimental group also took a teaching course on root canal therapy for the right mandibular first molar, but an animal model was used for the group. After the course was completed, the instructor conducted comprehensive evaluation of the students' psychological quality, patient communication skills, diagnosis and treatment logic, speed of performing procedures, and treatment plan design. A questionnaire survey was conducted to examine the students' attitudes toward and evaluation of animal model training., Results: The scores for psychological quality (0.430±0.024 vs. 0.115±0.036), patient communication skills (0.878±0.065 vs. 0.115±0.036), diagnosis and treatment logic (0.630±0.066 vs. 0.372±0.033), speed of performing procedures (0.8975±0.019 vs. 0.055±0.080), and treatment plan design (0.539±0.036 vs. 0.396±0.017) of the experimental group were significantly higher than those of the control group ( P <0.0001). The total score of the experimental group (3.374±0.184) was significantly higher than that of the control group (1.053±0.082) and the difference was statistically significant ( P <0.001). 95% of the students in the control group and 100% of those in the experimental group were willing to participate in animal model training to improve their level of diagnosis and treatment skills for dental and endodontic diseases, showing no statistically significant difference ( χ 2 =1.026, P =0.3112). In the experimental group, 30% of the students believed that their psychological qualities had been improved, 50% believed that their procedure skills had been improved, and 20% believed that animal model training had expanded the scope of their theoretical knowledge., Conclusion: Adding animal model training can improve dentistry graduate students' comprehensive abilities, including their psychological quality, patient communication skills, diagnosis and treatment logic, speed of performing procedures, and treatment plan design. In addition, it helps students familiarize themselves in advance with animal experimental operations for basic research, thus helping them acquire dual professional skills., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)