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Jun-Xiang Wang,1,* Jia-Hui Zhang,1,* Mu Guo,1,* Wei-Rui Huang,1 Han-Lu Zheng,1 Yi-Qi Liao,1 Ying-Xue Yan,1 Zhao-Long Lin,1 Neng-Fu Qiu,1 Cui-Ting Dai,2 Xiang-Bin Yu,1 Yue Yu1 1School of Pharmacy & Fujian Center for New Drug Safety Evaluation, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2Department of Pathology, The People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yue Yu; Xiang-Bin Yu, Email yyu@fjmu.edu.cn; yxb4666@fjmu.edu.cnIntroduction: Given the limitations and adverse effects of current rheumatoid arthritis (RA) treatments, there is an urgent need for safer and more effective therapeutic options. Levamisole (LVM) is a non-specific immunomodulator with potential for treating skin diseases, tumors, and autoimmune disorders. Recognizing LVM’s potential despite its controversial reputation, this study aimed to investigate its safety profile and therapeutic efficacy towards RA.Methods: To evaluate the potential toxicity of LVM, a 28-day oral administration was conducted in SD rats, assessing general toxicity and neurotoxicity using serum biochemical indicators, the Morris water maze test, transmission electron microscopy, and H&E staining. Subsequently, the therapeutic effects of LVM on RA were evaluated.Results: The results showed that 30 mg/kg LVM has promising therapeutic effects in the treatment of RA with negligible toxicity from 45 mg/kg to 180 mg/kg.Discussions: This study provides valuable preclinical data on the safety and efficacy of LVM, laying the groundwork for future clinical applications and potentially offering a safer and more effective treatment option for RA patients.Keywords: levamisole, general toxicity, neurotoxicity, rheumatoid arthritis

Jue-Xin Wang,1– 3,* Shi-Jia Yu,4,* Gang Huang,1,2 Yan-Bo Yu,1,2 Yan-Qing Li1,2 1Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province, 250012, People’s Republic of China; 2Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province, 250012, People’s Republic of China; 3Department of Gastroenterology, The First Affiliated Hospital of Weifang Medical College, Weifang People’s Hospital, Weifang, Shandong Province, People’s Republic of China; 4Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan-Bo Yu, Email yuyanbo2000@126.comAbstract: The intestinal barrier system protects the human body from harmful factors, by continuously renewing the intestinal epithelium, tight junctions and enteric microbes. However, dietary fat can harm the intestinal epithelial barrier enhancing gut permeability. In recent years, Apolipoprotein A-I has attracted much attention because of its anti-inflammatory properties. Numerous studies have demonstrated that Apolipoprotein A-I can regulate mucosal immune cells, inhibit the progression of inflammation, promote epithelial proliferation and repair, and maintain physical barrier function; it can also regulate angiogenesis, thereby improving local circulation. This article is intended to elucidate the mechanism by which Apolipoprotein A-I improves intestinal barrier damage caused by dietary fat and to review the role of Apolipoprotein A-I in maintaining intestinal homeostasis.Keywords: intestinal barrier, apolipoprotein A-I, dietary fat, gut microorganism, angiogenesis

Jian-Xiong Wang,&ast; Xu Zhao,&ast; Sheng-Qian Xu Department of Rheumatology & Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sheng-Qian Xu, Email xsqian-1112@163.comBackground: Long non-coding RNAs (lncRNAs) are important regulators in ankylosing spondylitis (AS). Few studies have examined the lncRNA-RNA binding protein (RBP) interaction in AS. This study performed bioinformatics analysis and clinical verification to identify key lncRNAs and propose their RBP interaction.Methods: Three GEO datasets of AS were analyzed by differential expression analysis. The differentially expressed lncRNAs between the AS and control groups were screened out, and the intersecting lncRNAs were regarded as target lncRNAs. Functional was performed to identify target lncRNAs by enrichment analysis, co-expressed RNA analysis, and lncRNA-RBP interaction analysis. Finally, this study analyzed the differential expression level and clinical value of lncRNAs between the AS and control groups.Results: Linc00304, linc00926, and MIAT were differentially expressed and upregulated. Enrichment analysis indicated that the key KEGG terms were the T-cell receptor signaling pathway and B-cell receptor signaling pathway. The key molecular function term was protein binding, and the key biological process term was adaptive immune response. In qRT-PCR results, 44 samples were validated. linc00304 expression was positively correlated with bath ankylosing spondylitis disease activity index (BASDAI), bath ankylosing spondylitis functional index (BASFI), erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). linc00926 expression was only positively correlated with ESR, whereas MIAT expression was positively correlated with BASFI, ESR, and CRP. Logistic regression revealed that linc00304, ESR, and CRP were the independent risk factors for BASDAI activation. The area under the curve (AUC) of serum linc00304 level in the diagnosis of AS was 0.687 (cutoff value: 0.413, specificity: 0.423, sensitivity: 0.900). AUC of linc00926 was 0.664 (cutoff value: 0.299, sensitivity: 0.882, specificity: 0.417). AUC of MIAT was 0.623 (cutoff value: 0.432, specificity: 0.443, sensitivity: 0.890) (all P < 0.05).Conclusion: Overall, this study uncovered three novel lncRNAs, which were upregulated in AS, and proposed a new lncRNA-RBP-mRNA interaction that might regulate adaptive immune response.Keywords: ankylosing spondylitis, long non-coding RNA, RNA binding protein, RNA sequencing

He-xiang Zong, Sheng-qian Xu, Jian-xiong Wang, Yi-ran Chu, Ke-ming Chen, Cong Wang, Wan-qiu Tong, Xi-le Wang Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Sheng-qian Xu, Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, No. 218, Ji-xi Road, Hefei, Anhui, 230022, People’s Republic of China, Tel +86 551 62922261, Fax +86 551 62923040, Email xsqian-1112@163.comPurpose: Non-steroidal anti-inflammatory drugs (NSAIDs) have generally been viewed as first-line therapy for axial spondyloarthritis (axSpA). Imrecoxib is a selective COX-2 inhibitor developed independently in China. At present, only one single-center RCT trial has shown that imrecoxib is equally effective as celecoxib in treating axSpA. Based on real-world data, our study aims to explore the efficiency of imrecoxib and TNF inhibitor (TNFi) combined with imrecoxib in treating axSpA.Patients and Methods: A total of 163 patients with axSpA who had more than two follow-up records in 6 months and treated with imrecoxib/celecoxib/TNFi combined with imrecoxib/TNFi combined with celecoxib from the First Affiliated Hospital of Anhui Medical University SpA Real World Database (AHSpA) were selected for analysis of our study. The linear mixed model was used to compare efficacy indexes before and after treatment and between different groups, adjust baseline measurement value and follow-up time. The Kaplan–Meier survival analysis was used to identify the differences in cumulative clinical remission rates between groups with different treatment at the follow-up period.Results: Results showed that after treatment ASDAScrp was slightly improved in imrecoxib group and celecoxib group within 6 months (p < 0.05). CRP, ESR, BASDAI, ASDAScrp, BASFI, occiput to wall distance and finger floor distance all significantly improved in TNFi combined with imrecoxib group and TNFi combined with celecoxib group within 6 months (all p < 0.05). According to the Kaplan–Meier survival curve and Log rank test analysis, the clinical remission rate was not significantly different between different treatment during 24-month follow-up (all p > 0.05).Conclusion: ASDAScrp improved slightly within 6 months after treatment with imrecoxib, and TNFi combined with imrecoxib significantly improved multiple effect indexes in axSpA patients. The efficacy of imrecoxib and celecoxib in the treatment of axSpA is equivalent. Also, they have the same efficacy after being combined with TNFi.Keywords: axial spondyloarthritis, imrecoxib, celecoxib, TNF inhibitor

Xia Li,1,2 Jun-Xi Wang,1 Yu-Ping Wang,1 Jia-Xin Shen,1 Yi-Xing Zheng,1 Pei-Hong Zhang,1 Jing-Jing Wei,1 Ze-Hao Zhuang1 1Endoscopy Center, First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Endoscope Room, Changle District Hospital, Fuzhou, People’s Republic of ChinaCorrespondence: Ze-Hao Zhuang, Endoscopy Center, First Affiliated Hospital of Fujian Medical University, 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People’s Republic of China, Tel +860591-87981370, Fax +860591-87981371, Email zehaozhuang@fjmu.edu.cnObjective: To compare indications, success rates and complications of pull [P] and introducer [I] techniques for percutaneous endoscopic gastrostomy (PEG).Methods: In this retrospective study, inpatients who underwent primary PEG tube insertion between January 2015 and February 2020 at the Endoscopy Center of the First Affiliated Hospital of Fujian Medical University were included.Results: A total of 103 inpatients were included in this study (P group, n = 67; I group, n = 36). The rates of tube replacement within first six months in the P and I groups were 1.5% and 11.1%, respectively (P = 0.049). The most common primary indication of PEG was malignancy. The proportion of patients with esophageal cancer was significantly lower in the P group (24.4% vs 54.2%, P = 0.015). No significant difference was found in the overall, major, or minor complications between the two groups. In patients with esophageal stenosis, the pull method was a risk factor for complications (P = 0.03; odds ratio [OR] = 12, 95% confidence interval [CI]: 1.164– 123.684). Logistic regression analysis showed that the risk factors for major and minor complications were the admission-to-gastrostomy interval (OR = 1.078, 95% CI: 1.016– 1.145, P = 0.014) and lack of antibiotic use (OR = 4.735, 95% CI: 1.247– 17.979, P = 0.022), respectively.Conclusion: Both PEG techniques have high clinical success rates. The introducer technique is more suitable for patients with esophageal stricture, which has lower minor complications, but higher rate of tube replacement compared to the pull technique. Use of antibiotics may reduce minor complications following PEG. Early PEG insertion may help to reduce post-PEG major complications.Keywords: endoscopy, gastrostomy, enteral nutrition, indications, complications

Li Lian,1,&ast; Jian-Xiong Wang,1,&ast; Yue-Chen Xu,2 He-Xiang Zong,1 Yu-Zhu Teng,1 Sheng-Qian Xu1 1Department of Rheumatology & Immunology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, People’s Republic of China; 2Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sheng-Qian Xu, Department of Rheumatology & Immunology, the first Affiliated Hospital of Anhui Medical University, No. 218, Ji-xi Road, Hefei, 230022, Anhui, People’s Republic of China, Tel/Fax +86 551 62922262, Email xushengqian16@sina.comPurpose: Osteoporosis (OP) has been classically considered a co-morbidity of rheumatoid arthritis (RA). This investigation determined the clinical significance of sarcopenia in patients with RA combined with OP or whether sarcopenia influences RA when combined with OP.Materials and Methods: Data pertaining to the duration of RA, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) were collected from 549 RA cases and 158 healthy individuals. Disease activity score at 28 joints (DAS28), the body mass index (BMI), health assessment questionnaire (HAQ), bone mineral density (BMD), and Sharp score were compared between the 2 groups.Results: The prevalence of OP (33.3% vs 12.7%, χ2= 69.992, P < 0.0001) and sarcopenia (61.7% vs 9.0%, χ2= 135.336, P < 0.01) was greater in patients with RA than in healthy controls. RA patients with sarcopenia had a higher incidence of OP at all measured sites than RA patients without sarcopenia (all P < 0.0001), and the incidence of OP was significantly higher than in patients with mild-to-moderate or severe RA without sarcopenia (P < 0.0001). Differences in age, gender, course of disease, CRP level, ESR, DAS28, BMI, HAQ, BMD, and Sharp score were statistically different between the RA with or without sarcopenia groups (P < 0.01). The incidence of OP and sarcopenia was higher in RA patients treated than not treated with glucocorticoids [GCs] (36.4% vs 29.3%, P < 0.05 and 66.1% vs 56.0%, respectively; P < 0.05). Logistic regression showed that the risk factors for OP in RA individuals were female (OR, 14.671; 95% CI, 6.877– 31.300; P < 0.0001), age (OR, 1.100; 95% CI, 1.076– 1.124; P < 0.0001), and sarcopenia (OR, 3.561; 95% CI, 2.214– 5.726; P < 0.0001).Conclusion: OP and sarcopenia are common in RA patients. Sarcopenia may be a risk factor for OP occurrence in Chinese patients with RA.Keywords: rheumatoid arthritis, osteoporosis, sarcopenia, muscle

Dan Peng, Zi-Liang Hou, Hong-Xia Zhang, Shuai Zhang, Shu-Ming Zhang, Rui-Yan Lin, Zhen-Chuan Xing, Yuan Yuan, Kai-Yuan Yang, Jin-Xiang Wang Department of Respiratory and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jin-Xiang WangDepartment of Respiratory and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Xinhuananlu No. 82, Tongzhou District, Beijing, 101100, People’s Republic of ChinaEmail jinxiangwang@ccmu.edu.cnBackground: Pulmonary thromboembolism (PTE) is a common disease which may be a serious condition and has high mortality. Recently, it has been shown that circRNAs play an important role in the development of various diseases, including thromboembolic disease. However, circRNAs expression profiling is not clear in PTE, this study aims to identify the circRNAs expressed in PTE and to elucidate their possible role in pathophysiology of PTE.Methods: A total of 5 patients with CTPA-confirmed PTE and 5 healthy controls were recruited for the present study. The circRNAs expression profile was analyzed by microarray.Results: In total, 256 differentially expressed circRNAs (up 142, down114) and 1162 mRNA (up 446, down 716) were summarized by analyzing the circRNAs microarray data. The top 3 up-regulated and 3 down-regulated circRNAs were validated by Real-Time Polymerase Chain Reaction (qRT-PCR). Two differentially expressed circRNAs (hsa_circ_0000891, hsa_circ_0043506) were selected for further analysis. Finally, we construct a circRNA-miRNA-mRNA ceRNA network with a bioinformatic prediction tool. Pathway analysis shows that the enriched mRNAs targets take part in Protein processing in endoplasmic reticulum, Systemic lupus erythematosus, Endocytosis, Spliceosome, HTLV-I infection and Ubiquitin mediated proteolysis.Conclusion: Our findings indicated that aberrantly expressed circRNAs (hsa_circ_0000891, hsa_circ_0043506) may be involved in the development of PTE.Keywords: circRNA, gene, pulmonary thromboembolism, circRNA-miRNA-mRNA network, functional enrichment

Hao-Ran Wu,1 Chuan-Qi Wang,1 Jie-Xin Wang,1,2 Jian-Feng Chen,1,2 Yuan Le1,2 1State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China; 2Research Center of the Ministry of Education for High Gravity Engineering and Technology, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of ChinaCorrespondence: Yuan LeState Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing, Chaoyang District 100029, People’s Republic of ChinaEmail leyuan@mail.buct.edu.cnBackground: Oil-in-water drug nanoemulsion forms drug delivery systems with high oral bioavailability. The conventional fabrication methods of nanoemulsion are low energy emulsification methods and high energy emulsification methods. However, both two methods are not ideal for industrial production. The problem of low energy emulsification methods is the high dosage of surfactant and co-surfactant which has potential biosecurity issues. What is more, high energy emulsification methods have some disadvantages, like the destruction of drug components, the price of equipment and the difficulties of industrial production. Hence, there have been a few commercial drug nanoemulsions so far.Methods: In this work, we reported a novel method for the fabrication of stable and transparent drug nanoemulsion which contains hydrophilic drug rosuvastatin (ROS) calcium or hydrophobic drug silybinin (SYN) by using high-gravity rotating packed bed (RPB). The drug nanoemulsion was systematically characterized by droplet size, size distribution, stability and in vitro drug release as well as Caco-2 cells permeability.Results: Compared with the self-emulsification method (SE), high-gravity technology could reduce 75% amount of mixed surfactants. The as-prepared nanoemulsion exhibited a very narrow droplet size distribution with a size of 13.53 ± 0.53 nm and a polydispersity index of 0.073 ± 0.018. Meanwhile, the drug nanoemulsion was physicochemically stable at 25°C and 4°C for one-year storage. Furthermore, both ROS and SYN nanoemulsion displayed higher cell permeability and in vitro dissolution than that of commercial formulations.Conclusion: These results demonstrate that RPB can be a potential device to facilitate the industrial production of drug nanoemulsion.Keywords: nanoemulsion, high-gravity rotating packed bed, Rosuvastatin calcium, Silybinin, stability, in vitro dissolution, Caco-2 permeability

Jin-Xiang Wang,1 Hui-Qiao Li,1 Fang Zhang,2 Wei Ning31Department of Pulmonary and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Pulmonary Function Test Room, Department of Pulmonary and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jin-Xiang WangDepartment of Pulmonary and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of ChinaTel +86 10 6954 3901 Ext. 1125Email wangjx0090@sina.comObjective: To evaluate patients with stable COPD for the presence of potentially pathogenic microorganisms (PPM), systemic inflammation and the effects of short-term antibiotic therapy in PPM positive patients.Methods: From January 2016 to June 2017, we enrolled 96 stable COPD patients. Bacterial cultures from sputum collections were quantitated, along with markers for systemic inflammation including serum C-reactive protein (CRP), interleukin-8 (IL-8) and plasma fibrinogen (FIB) in all patients. All enrolled patients were followed for 12 months. Forty patients were identified as PPM positive and were randomly divided into an antibiotic group and a control group. The antibiotic group was treated with moxifloxacin orally for 6 days. Lung function and markers for systemic inflammation were repeatedly measured at 30 days and 6 months in PPM positive subjects.Results: Binary logistic regression analysis showed that risk factors for PPM positive are bronchiectasis (OR 4.18, 95% CI 1.20–14.59; P=0.025), COPD assessment test (CAT) ≥20 (OR 17.55, 95% CI 2.82–109.18; P=0.002), spontaneous sputum (OR 15.09, 95% CI 1.36–168.02; P=0.027) and sputum purulence (OR 38.43, 95% CI 5.39–274.21; P=0.000). CRP and IL-8 were higher in PPM positive group than those in PPM negative group (P=0.001, P=0.007, respectively), but there were no differences of FIB between the two groups (P=0.086). Compared to the PPM negative group, the rate of acute exacerbation of COPD was higher (P=0.029) and time to next acute exacerbation was shorter (P=0.030) in PPM positive group. There were no differences in lung function and systemic inflammatory markers either in the control group or the antibiotic group at different time points of follow-up.Conclusion: PPM exists in stable COPD patients and can cause systemic inflammation and is associated with acute exacerbation of COPD. Short-term antibiotic therapy had no effect on systemic inflammation nor on acute exacerbation of COPD.China Clinical Trials Registry: ChiCTR-IOR-15006769Keywords: COPD, potentially pathogenic microorganisms, systemic inflammation, antibiotics, C-reactive protein, interleukin-8

Yichen Huang,1,* Xing Shi,2,* Zhiyong Li,1,* Yang Shen,1,* Xinxin Shi,1 Liying Wang,3 Gaofei Li,3 Ye Yuan,2 Jixiang Wang,4 Yongchao Zhang,4 Lei Zhao,4 Meng Zhang,4 Yu Kang,2 Ying Liang1 1National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China; 2CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; 3Department of Psychiatry, Beijing Hospital of Chinese Traditional and Western Medicine, Beijing, China; 4Beijing Gene Tangram Technology Co. Ltd, Beijing, China *These authors contributed equally to this work Background: Gut microbiota can affect human behavior and mood in many ways. Several studies have shown that patients with depression were also accompanied with gut microbiota disorder, in which Firmicutes are related to the protective function of intestinal barrier. In this study, we explore the changes and effects of Firmicutes in the patients with major depressive disorder (MDD). Method: We recruited 54 subjects, including 27 patients with MDD. Fecal samples were collected for identification by 16S rRNA sequencing and bioinformatics analysis. Results: The study shows that the alpha diversity indices of MDD patients are lower than those of the healthy controls. Firmicutes is the most significantly decreased phylum in the MDD samples. There are totally 13 taxonomic biomarkers with P-value

Wei Gan,1 Mei-Xia Zhang,1,2 Jia-Xing Wang,3 Yi-Peng Fu,1 Jin-Long Huang,1 Yong Yi,1 Chu-Yu Jing,1 Jia Fan,1 Jian Zhou,1 Shuang-Jian Qiu1,2 1Department of Liver Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, People’s Republic of China; 2Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China Background: Radical resection is the treatment of choice for hepatocellular carcinoma (HCC). However, even with this treatment, HCC prognosis and the efficacy of current predictive models for such patients remain unsatisfactory. Here, we describe an accurate and easy-to-use prognostic index for patients with HCC who have undergone curative resection.Methods: The study population comprised of 1,041 patients with HCC who underwent curative resection at Zhongshan Hospital. This population was reduced to 768 patients who were treated in 2012 analyzed as the training cohort and 273 patients treated in 2007 who were used as a validation cohort.Results: The lactic dehydrogenase to albumin ratio (LAR) was identified as a significant prognostic index for both overall survival and recurrence-free survival in two independent cohorts. The optimal cutoff value for LAR was determined to be 5.5. The C-index of LAR was superior to other inflammatory scores and serum parameters. This biomarker was also shown to be a stable predictive index in the validation cohort. The new nomogram combining LAR with the Barcelona Clinic Liver Cancer staging system had an improved ability to discriminate overall survival and recurrence-free survival. Nomogram predictions were consistent with observations based on calibration and decisive curve analysis in both independent cohorts.Conclusion: LAR is a novel, convenient, reliable, and accurate prognostic predictor in patients with HCC undergoing curative resection. Our results suggest the recommendation of LAR to be used in routine clinical practice. Keywords: hepatocellular carcinoma, lactic dehydrogenase, LAR, nomogram, survival

Xianglong Ding,1 Lei Zhou,1 Jingxu Wang,2 Qingxia Zhao,3 Xi Lin,1 Yan Gao,1 Shaobing Li,4 Jingyi Wu,1 Mingdeng Rong,4 Zehong Guo,1 Chunhua Lai,1 Haibin Lu,4 Fang Jia11Center of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, 2Department of Stomatology, The First Affiliated Hospital of Guangzhou Medical University, 3Department of Stomatology, Nanfang Hospital, 4Department of Periodontics and Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaAbstract: In the present work, a hierarchical hybrid micro/nanostructured titanium surface was obtained by sandblasting with large grit and acid etching (SLA), and nanotubes of different diameters (30 nm, 50 nm, and 80 nm) were superimposed by anodization. The effect of each SLA-treated surface decorated with nanotubes (SLA + 30 nm, SLA + 50 nm, and SLA + 80 nm) on osteogenesis was studied in vitro and in vivo. The human MG63 osteosarcoma cell line was used for cytocompatibility evaluation, which showed that cell adhesion and proliferation were dramatically enhanced on SLA + 30 nm. In comparison with cells grown on the other tested surfaces, those grown on SLA + 80 nm showed an enhanced expression of osteogenesis-related genes. Cell spread was also enhanced on SLA + 80 nm. A canine model was used for in vivo evaluation of bone bonding. Histological examination demonstrated that new bone was formed more rapidly on SLA-treated surfaces with nanotubes (especially SLA + 80 nm) than on those without nanotubes. All of these results indicate that SLA + 80 nm is favorable for promoting the activity of osteoblasts and early bone bonding.Keywords: nanotopography, osseointegration, dental and orthopedic implant, titanium

Xiaoqing Wang,1 Hongli Shan,2 Jixue Wang,1 Yuchuan Hou,1 Jianxun Ding,3 Qihui Chen,1 Jingjing Guan,1 Chunxi Wang,1 Xuesi Chen31Department of Urology, the First Hospital of Jilin University, 2Department of Clinical Laboratory, the First Hospital of Jilin University, 3Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, People’s Republic of ChinaAbstract: A tubular poly(ε-caprolactone) (PCL)/poly(lactide-co-glycolide) (PLGA) ureteral stent composed of nanofibers with micropores was fabricated by double-needle electrospinning. The stent was ureteroscopically inserted into six Changbai pigs, and the commercial polyurethane Shagong® stent was inserted into four pigs as control. Intravenous pyelography revealed that the PCL/PLGA stent gradually degraded from the distal end to proximal terminal, and all stents were completely degraded at 10 weeks post-insertion. No significant difference was observed in hydronephrosis severity between the two groups. The levels of serum creatinine and urine pH remained similar throughout the study in the two groups, but the number of white blood cells in the urine was significantly higher in the Shagong® stent group. On Day 70, histological evaluation indicated equivalent histological severity scores in the middle and distal ureter sections and bladder in the two groups. However, the PCL/PLGA stent-implanted pigs had significantly lower mean severity scores in the kidney and proximal ureter sites. These data revealed that the PCL/PLGA stent degraded in a controlled manner, did not induce obstruction, and had a lower urothelial impact in comparison to the Shagong® stent, indicating that the stent exhibited great potential for clinical application.Keywords: nanocomposites, polyesters, poly(ε-caprolactone), poly(lactide-co-glycolide), hydronephrosis severity

Recent research has placed episodic reinforcement learning(RL) alongside model-free and model-based RL on the list ofprocesses centrally involved in human reward-based learning.In the present work, we extend the unified account of model-free and model-based RL developed by Wang et al. (2017) tofurther integrate episodic learning. In this account, a genericmodel-free "meta-learner" learns to deploy and coordinate allof these RL algorithms. The meta-learner is trained on a broadset of novel tasks with limited exposure to each task, suchthat it learns to learn about new tasks. We show that whenequipped with an episodic memory system inspired by theoriesof reinstatement and gating, the meta-learner learns to use thesame pattern of episodic, model-free, and model-based RLobserved in humans in a task designed to dissociate among theinfluences of these learning algorithms. We discuss implicationsand predictions of the model.

The vortex-induced vibration behavior and mechanism of an asymmetrical composite beam cable-stayed bridge is investigated by means of aerodynamic sectional tests and computational fluid dynamics methods. Tests are performed for the bridge deck under five wind attack angles (0°, ±2.5°, and ±5°) and two wind directions (0° and 180°) during the completion and construction stages. The influence of damping ratios, wind barriers, and vehicles on the vortex-induced vibration behaviors of the bridge deck is examined. The test and simulation results show that the properties of the vortex-induced vibrations vary with the wind direction as a result of the asymmetry of the main girder. The vertical maximum vortex-induced vibration amplitude of the bridge deck was found to occur at the wind attack angle of −5° and wind direction of 180°, while the torsional maximum was found at the wind attack angle of −5° and wind direction of 0°. Both vehicles and wind barriers have amplification effects on the vortex-induced vibrations of the bridge deck when the wind direction is 180°. The vortex-induced vibration of the bridge deck can be effectively mitigated when the damping ratio increases from 0.5% to 1.5%. The vortex-induced vibration mechanism of the bridge deck under different wind directions can be attributed to the same vortex shedding mode (the Kelvin–Helmholtz vortex and the Kármán vortex street). While, the location of the vortex generation and direction of the vortex shedding at the wake are strongly influenced by the wind directions, resulting in the variation of the vortex-induced vibration properties of the bridge deck with the wind direction. This study provides a guideline for the design of bridges with asymmetrical main girders to suppress the VIV. [ABSTRACT FROM AUTHOR]

Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor. We investigated the distribution and morphological characteristics of ghrelin-immunopositive (ghrelin-ip) cells in the African ostrich adrenal gland. We found that the adrenal gland of the African ostrich consisted of three parts: capsule, inter-renal tissue and chromaffin cells. The inter-renal tissue and chromaffin cells interdigitated irregularly. The inter-renal tissue consisted of a peripheral zone and a central inner zone. The peripheral zone could be divided into an outer subcapsular zone and an inner zone. The subcapsular zone cells were arranged as a bow, while the inner area cells formed cords that were perpendicular to the capsule. The central inner zone exhibited irregular clumps and the cells were morphologically similar to chromaffin cells. Ghrelin-ip cells were located throughout the adrenal gland except the capsule. The majority of ghrelin-ip cells were found among the chromaffin cells. The number of ghrelin-ip cells in the inter-renal tissue decreased gradually from the central inner zone, to the inner zone to the subcapsular zone. The ghrelin-ip cells were oval or irregular in shape and exhibited cytoplasmic staining. Our findings suggest that ghrelin may play a role in regulating adrenal hormone secretion in the African ostrich. [ABSTRACT FROM AUTHOR]

Background: Compared with current methods used to assess schizophrenia, near-infrared spectroscopy (NIRS) has the advantages of providing noninvasive and real-time monitoring of functional activities of the brain and providing direct and objective assessment information., Aim: To explore the research field of NIRS in schizophrenia from the perspective of bibliometrics., Methods: The Web of Science Core Collection was used as the search tool, and the last search date was April 21, 2024. Bibliometric indicators, such as the numbers of publications and citations, were recorded. Bibliometrix and VOS viewer were used for visualization analysis., Results: A total of 355 articles from 105 journals were included in the analysis. The overall trend of the number of research publications increased. Schizophrenia Research was identified as an influential journal in the field. Kasai K was one of the most influential and productive authors in this area of research. The University of Tokyo and Japan had the highest scientific output for an institution and a country, respectively. The top ten keywords were "schizophrenia", "activation", "near-infrared spectroscopy", "verbal fluency task", "cortex", "brain, performance", "working-memory", "brain activation", and "prefrontal cortex"., Conclusion: Our study reveals the evolution of knowledge and emerging trends in the field of NIRS in schizophrenia. the research focus is shifting from underlying disease characteristics to more in-depth studies of brain function and physiological mechanisms., 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.)

Cutting-edge techniques utilizing continuous films made from pure, novel semiconductive materials offer promising pathways to achieve high performance and cost-effectiveness for X-ray detection. Semiconductive metal-organic framework (MOF) glass films are known for their remarkably smooth surface morphology, straightforward synthesis, and capability for large-area fabrication, presenting a new direction for high-performance X-ray detectors. Here, a novel material centered on MOF glasses for highly uniform glass film fabrication customized for X-ray detection is introduced. MOF glasses, composed of zinc and imidazole derivatives, enable the transition from solid to liquid at low temperatures, facilitating the straightforward preparation of large-area and continuous MOF films with high mobility for X-ray device fabrication. Remarkably, MOF glass detectors demonstrate an exceptional sensitivity of 112.8 µC Gy air -1 cm -2 and a detection limit of 0.41 µGy air s -1 , making them one of the most sensitive and with the best detection limits reported to date for MOF X-ray detectors. Clear X-ray images are successfully conducted using these developed MOF glass detectors for the first time. This breakthrough in X-ray sensitivity, and detection limit along with the spatial imaging resolution establishes a new standard for developing large-area and efficient MOF-based X-ray detectors with practical applications in medical and security screening., (© 2024 Wiley‐VCH GmbH.)

School bullying occurs frequently in primary and secondary schools, which is a global problem and it often brings serious physical and mental harm to the victims. When school bullying occurs, there may be a large number of bystanders in addition to the bullies and victims. What actions bystanders take affects the progress of school bullying. Relevant studies indicate that social norms including how peers around them react (descriptive norms) and how important adults such as teachers and parents demand (injunctive norms) play important roles in bystanders' action-taking, but limited studies have considered individual differences. Therefore, this study used a person-centered approach to explore the co-existence patterns of social norms and bystanders' defending intention to further understand their relations. We surveyed 1,384 junior high school students in China by self-report questionnaires, and they were asked to assess their defending intention when witnessing school bullying events under different contexts of social norms. Through latent profiles analysis, five co-existing patterns were identified: no norms-no defending group (4.8%), parent norms-no defending group (3.6%), weak norms-low defending group (24.3%), teacher-peer norms-medium defending group (40.6%), teacher-peer norms-high defending group (26.7%). In four out of the five patterns, students' levels of defending intention were highly consistent with the levels of peer and teacher norms, but largely contradicted parent norms. This suggests that descriptive norms from peers and injunctive norms from teachers, other than those from parents are crucial for promoting bystanders' defending intention, which provides important enlightenment for school bullying prevention. These findings provide important enlightenment for the prevention and control of school bullying in the future., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

The strong western Pacific boundary current of the Kuroshio significantly affects the oceanographic and ecological processes of the East China Sea through its branches. To understand the seasonal variation of Kuroshio intrusion and its ecological effects, 10 cruises were conducted from February 2015 to January 2016 in the waters adjacent to the Changjiang River estuary to collect hydrological data and abundances of phytoplankton assemblages of Prochlorococcus (Pro), Synechococcus (Syn) and picoeukaryotes. High salinity bottom water representing the Nearshore Kuroshio Branch Current (NKBC) appeared in the spring, peaked in the summer, and then almost disappeared at the end of the autumn. During this period, the seasonal variations of Pro and Syn subgroup with lower orange fluorescence (dim type Syn) abundances correlated and synchronized with the intensity of the NKBC intrusion. Water masses analysis further illustrated that the spring was the critical season for NKBC to influence and transport phytoplankton along the pathway to coastal waters. NKBC will further impact the phytoplankton dynamics and ecological processes in this sea area., 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.)

Background: Urethral plate (UP) reserved Onlay urethroplasty is currently used widely in mid-distal hypospadias. However, for children with 15-30° residual curvature after degloving, only dorsal tunica albuginea plication is performed to correct penile ventral curvature (VC), and long-term follow-up showed a high recurrence rate of penile curvature. We developed a modified Onlay urethroplasty, which dissociates the UP and completely removes the tissue beneath the UP to fully correct penile curvature. Furthermore, we compared it with the standard Onlay urethroplasty to explore its rationality and feasibility., Methods: We prospectively collected clinical data from 68 children with hypospadias who underwent standard or modified Onlay urethroplasty between September 2019 and June 2021, and evaluated the interim outcomes to identify the complications between the two groups. Additionally, we conducted histological examination of the tissue beneath the UP., Results: A total of 32 patients underwent modified Onlay urethroplasty. Intraoperative curvature measurements showed that 37.5% (12/32) of the patients had completely straightened their penis after UP dissection and removal of the fibrous tissue beneath it. A total of 36 patients underwent standard Onlay urethroplasty. Totally, five fistulas each were reported in the first and second groups, and the complication rates were 15.6% and 13.9%, respectively (P > 0.05). The histological results showed that the tissue below the UP contains a large amount of collagen, mainly type I collagen., Conclusion: The dissociated UP Onlay urethroplasty can maximally remove factors limiting penis growth and completely correct penile curvature, without increasing the incidence of postoperative complications. Therefore, we recommend the application of the improved Onlay urethroplasty in children with mid-distal hypospadias., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Renal denervation (RDN) has been used for treating resistant hypertension. A few recent studies have shown vagal innervation of kidneys causing confusion. This study aimed to provide anatomical and functional evidence for renal autonomic innervation. Experiments were performed in male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Pseudorabies virus (PRV) in the paraventricular nucleus and rostral ventrolateral medulla was prevented by bilateral RDN, but not subdiaphragmatic vagotomy. PRV did not appear in the dorsal motor nucleus of the vagus and nucleus tractus solitarii 72 h after renal injection of PRV. Adrenergic fibers were approximately seven times more than cholinergic fibers in the main renal artery (MRA) and its first (1RA) and second grade (2RA) branches. Adrenergic fibers in 1RA were more than those in MRA and 2RA. Tyrosine hydroxylase immunoreactivity in these arteries was higher in SHR than in WKY. Norepinephrine (NE) increased and α-receptor antagonist reduced vascular ring tension of renal arteries. The effect of NE was greater in 1RA and 2RA than in MRA, which was prevented by α-receptor antagonist. Acetylcholine (ACh) or blockage of β-receptors, M receptors, or N receptors had no significant effects on vascular ring tension and the effect of NE. Renal blood flow was reduced by electrical stimulation of renal nerves but not affected by stimulation of the subdiaphragmatic vagus. These results provide anatomical and functional evidence that kidneys are innervated and renal blood flow is regulated by renal sympathetic nerves rather than the vagus. Renal vasoconstriction is regulated by NE and adrenergic fibers rather than ACh or cholinergic fibers in WKY and SHR. NEW & NOTEWORTHY Kidneys are innervated by renal nerves rather than the vagus. Adrenergic fibers in renal arteries are about seven times more than cholinergic fibers. Renal vasoconstriction is regulated by norepinephrine and adrenergic fibers rather than acetylcholine or cholinergic fibers. Renal blood flow is regulated by renal sympathetic nerves and is not affected by the vagus. These findings provide anatomical and functional evidence for renal autonomic innervation in normotensive and hypertensive rats.

Polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder characterized by abnormal elevation in hormone levels, with currently lacking effective treatment options. N-3 polyunsaturated fatty acids (PUFA) have broad pharmacological activity and play a beneficial role in the development of PCOS. In this study, we observed that n-3 PUFA-eicosatrienoic acid (ETA) improves the estrous cycle and ovarian morphology in dehydroepiandrosterone (DHEA)-induced PCOS mice, particularly serum hormone levels. Additionally, it suppresses the expression of CYP19A1 and E2 synthesis in human granulosa-like tumor cell line (KGN) cells. Further investigation revealed that ETA significantly upregulates the expression of CD36, cAMP, P-PKA, and FOXO1 in KGN cells and mouse ovaries to lower E2 levels. This conclusion was supported by inhibiting CD36 and FOXO1 at both the mouse and cellular levels. Additionally, ETA treatment decreased the expression of ESR1, Kiss1, Gnrh in the hypothalamus, and GnRHR, Lhβ, Egr1, Pitx1, Sf1 in the pituitary of PCOS mice. No differences were observed after ETA treatment in the CD36 and FOXO1 inhibitor groups, indicating that ETA improves PCOS mice by regulating the hypothalamic-pituitary axis through E2 synthesis inhibition. In summary, we have elucidated for the first time the mechanism by which CD36 regulates E2 synthesis in ovarian granulosa cells and demonstrated that ETA activates the CD36 receptor to inhibit E2 synthesis through the cAMP/PKA/FOXO1/CYP19A1 signaling pathway, thereby improving hormonal imbalance and treating PCOS. This provides a new strategy for the effective prevention and treatment of PCOS., 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.)

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13 C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 ., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Context: The safety and efficacy of nutritional management for pressure injuries (PIs) have been the subjects of ongoing interest. Some evidence demonstrated that nutrition is essential for skin and tissue viability, supporting tissue repair for healing the pressure injury., Objective: This investigation aimed to systematically review clinical practice guidelines (CPGs) for the nutritional management of PIs and furnish an evidence map to assess research trends and CPG gaps., Methods: The PubMed, Embase, and guidelines databases, and society websites were searched for CPGs for the nutritional management of PIs. The basic recommendations for the nutritional management of PIs, method quality, and reporting CPGs quality were identified and imported into Excel. Four researchers independently elucidated each CPG's quality via the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument and the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist. All bubble charts were generated using Excel software., Results: This review included 12 CPGs with a combined 23 recommendations. The nutrition screening and assessment were summarized on the basis of the PI recommendations for 6 major items, 12 items on nutrition management, and 3 on PI education. The assessed CPGs had mixed quality, and the highest score  ± standard deviation based on the clarity of presentation was 83.46 ± 7.62, whereas the lowest mean score based on AGREE II applicability was 53.31 ± 16.90. Field 1 (basic information) in the RIGHT checklist had the greatest reporting rate (68.06%), whereas field 5 (review and quality assurance) had the lowest CPGs quality (41.67%)., Conclusion: This investigation furnishes an evidence map and provides new perspectives on the CPGs for the nutritional management of PIs. However, the CPGs included still need improvement, especially in the applicability and editorial independence domains., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Estrogen is thought to be the reason for the higher prevalence of papillary thyroid carcinoma (PTC) in fertile women; however, more study is required to completely comprehend how estrogen affects PTC development at the cellular level. Therefore, we combined Oxford Nanopore Technologies (ONT) sequencing to explore molecular markers of PTC and to investigate the molecular mechanisms by which estrogen promotes PTC development., Methods: The expression levels of ESR1 (ERα) and KRT19 in normal thyroid tissues and cancer tissues as well as in different cancer stages, races, genders, age groups, histological subtypes and nodular metastasis status of the TCGA database were analyzed online by Ualcan; the relationship between ESR1, KRT19 and the survival of THCA patients was analyzed. A PTC xenograft tumor model was established. An ERα specific inhibitor (MPP) was administered and an EDU cell proliferation assay was used to verify the effect of estrogen on PTC proliferation. KRT19 was knocked down in KTC-1 cells, and the proliferation, migration, and invasion abilities of PTC cells were determined using CCK-8, immunofluorescence labeling, Western blot for EMT-related proteins, scratch assay, and Transwell assay. The role of ERα in relation to KRT19 was investigated by Western blot and immunofluorescence. The effects of ERα/KRT19 signaling axis on the proliferation, migration and invasion ability of PTC cells were evaluated using EDU cell proliferation assay and Transwell. Using ONT sequencing, 15 pairs of PTC tissue and paracancer tissue samples were collected. A PPI network was constructed to validate the differential expression of KRT19 in combination with biosignature analysis, and the protein interaction between KRT19 and ESR1 was verified using STRING., Results: Ualcan showed that the expression of ESR1 and KRT19 was higher in THCA tissues than in normal thyroid tissues. E2 activation of ERα promoted the growth of PTC cells and tissues. si-KRT19 inhibited the proliferation, migration and invasion of PTC cells. KRT19 together with ERα formed the ERα/KRT19 signaling axis. E2 activation of the ERα/KRT19 signaling axis promoted the proliferation, migration, and invasion of PTC cells. ONT sequencing and STRING website verified that KRT19 is significantly differentially expressed in PTC and that ESR1 and KRT19 have protein interactions and are related to the estrogen signaling pathway., Conclusions: Using public databases, RNA sequencing, and bioinformatics, we discovered that E2 stimulates the ERα/KRT19 signaling axis to stimulate PTC proliferation, migration, and invasion., (© 2024. The Author(s).)

Wild species of domesticated crops provide valuable genetic resources for resistance breeding. Prunus davidiana, a wild relative of peach with high heterozygosity and diverse stress tolerance, exhibits high resistance against aphids. However, the highly heterozygous genome of P. davidiana makes determining the underlying factors influencing resistance traits challenging. Here, we present the 501.7 Mb haplotype-resolved genome assembly of P. davidiana. Genomic comparisons of the two haplotypes revealed 18,152 structural variations, 2,699 Pda&#95;hap1-specific and 2,702 Pda&#95;hap2-specific genes, and 1,118 allele-specific expressed genes. Genome composition indicated 4.1% of the P. davidiana genome was non-peach origin, out of which 94.5% was derived from almond. Based on the haplotype genome, the aphid resistance quantitative trait locus (QTL) was mapped at the end of Pda03. From the aphid resistance QTL, PdaWRKY4 was identified as the major dominant gene, with a 9-bp deletion in its promoter of the resistant phenotype. Specifically, PdaWRKY4 regulates aphid resistance by promoting PdaCYP716A1-mediated anti-aphid metabolite betulin biosynthesis. Moreover, we employed a genome design to develop a breeding workflow for rapidly and precisely producing aphid-resistant peaches. In conclusion, this study identifies a novel aphid resistance gene and provides insights into genome design for the development of resistant fruit cultivars., (© 2024 Institute of Botany, Chinese Academy of Sciences.)

Background: The association between plasma free fatty acid (FFA) and the outcomes in the heart failure (HF) patients remains unclear., Methods: A cohort study among HF patients was performed. Plasma FFA was analyzed as both a continuous and a categorical variable (grouped by tertiles) to assess its association with composite cardiovascular (CV) death and HF hospitalization (CV death & HHP), CV death alone, and all-cause mortality (ACM) using Cox regression models. Subgroup analyses of HF patients with preserved ejection fraction (HFpEF) and mildly reduced/reduced ejection fraction (HFmrEF/HFrEF) were performed. This work also assessed the effectiveness of combining FFA and NT-pro BNP biomarkers for risk stratification by calculating the concordance index (C-index)., Results: Among the 4,109 HF patients, FFA levels exceeding 0.4-0.42 mmol/L were associated with increased risks of the three outcomes. Patients in the highest FFA tertile faced greater risks than those in the lowest tertile. Adjusted hazard ratios were 1.32 (95% CI: 1.11-1.58) for CV death & HHP, 1.45 (95% CI: 1.16-1.82) for CV death, and 1.39 (95% CI: 1.15-1.68) for ACM, with a maximum follow-up of 8 years (median: 25 months). Subgroup analyses revealed that elevated FFA levels consistently predicted worse outcomes in both HFmrEF/HFrEF and HFpEF patients. The C-index for predicting outcomes was significantly greater when NT-pro BNP and FFA were combined than when NT-pro BNP was used alone (P < 0.01)., Conclusion: Increased plasma FFA concentrations were independently associated with greater risks of CV death & HHP, CV death, and ACM among HF patients, irrespective of the ejection fraction. The combination of FFA and NT-pro BNP biomarkers significantly improved risk stratification in HF patients., (© 2024. The Author(s).)

Novel scintillation materials have played an indispensable role in the recent remarkable progress witnessed for X-ray imaging technology. Herein, a high-performance X-ray scintillation screen was developed based on a highly efficient hybrid system combining inorganic ZnS (Ag) with thermally activated delayed fluorescence (TADF) scintillator materials via an interfacial energy transfer (EnT) mechanism. ZnS (Ag) has a high X-ray absorption capacity and functions as the initial layer for efficiently converting high-energy X-ray photons into low-energy visible light (acting as a sensitizer) while also serving as an energy donor. The TADF component, on the contrary, is an energy acceptor and forms an active scintillating layer. By harnessing TADF chromophores that can efficiently capture both singlet and triplet excitons, our composite material offers a remarkable spatial imaging resolution of 24 line pairs per millimeter, surpassing those of the majority of existing organic and inorganic scintillators. Further, our interfacial energy transfer strategy effectively amplifies the radioluminescence intensity of the TADF scintillator by a factor of 75, offering an outstanding light yield of 38,000 photons/MeV. This advancement represents a remarkable breakthrough in organic X-ray scintillation technology and is a notable achievement within the X-ray imaging field, paving the way for novel applications in medical imaging and security inspection.

Background: Previous evidence indicates that the NDC80 complex, a conserved spindle microtubule-binding component of the kinetochore, is overexpressed and associated with prognosis in certain cancer types. Herein, we assessed the expression and prognostic value of NDC80 complex components in pan-cancer and interrogated their potential functions in tumor context through multiple databases and software. Results: Our findings showed that the expression of NDC80 complex components was aberrant across almost all cancer types and correlated positively with poor prognosis at the pan-cancer level. Furthermore, the expression levels of NDC80 complex components were positively associated with Th2 cell infiltration in the majority of cancer types. Additionally, higher expression of the NDC80 complex components was associated with increased immune checkpoint gene expression and TP53 mutation in specific cancer types. We also discovered that NDC80 complex components play pivotal roles in cell division, and the cell cycle within the tumor context. Moreover, knockdown of NDC80 significantly suppressed cell growth and inhibited the G1-S phase transition in two breast cancer cell lines. Conclusions: Our study suggests that the NDC80 complex components could serve as reliable biomarkers for cancer detection and prognosis in pan-cancer, in addition to uncovering their role as cancer-promoting genes involved in Th2 cell infiltration, immune checkpoint, cell growth, and TP53 mutation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Sympathetic hyperactivity contributes to the pathogenesis of hypertension. However, it is unclear whether the excessive sympathetic activity is an independent and crucial factor for vascular remodeling in hypertension. This study focused on the effect of local sympathetic denervation with superior cervical ganglionectomy (SCGx) on vascular remodeling., Methods: Surgical bilateral SCGx was performed in 9-week-old male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Control rats received sham-operation without SCGx. All measurements were made 4 weeks after the surgery., Results: The effectiveness of SCGx was confirmed by the eye features of Horner syndrome, greatly reduced tyrosine hydroxylase (TH) contents in the superior cervical ganglion (SCG)-innervated arteries in the head. Although SCGx had no significant effects on blood pressure and heart rate in WKY and SHR, it attenuated vascular remodeling of facial artery and superficial temporal artery in SHR, two representative SCG-innervated extracranial arteries, without significant effects on non-SCG-innervated thoracic aorta and mesenteric artery. SCGx-treated SHR had more auricular blood flow and retina microvasculature than sham-operated SHR. However, SCGx had only a mild effect in attenuating the vascular remodeling of basilar artery and middle cerebral artery, two representative SCG-innervated intracranial arteries, in SHR. SCGx-treated SHR exhibited upregulation of α-smooth muscle actin, downregulation of proliferating cell nuclear antigen, and attenuation of oxidative stress and inflammation in facial artery and superficial temporal artery., Conclusions: Sympathetic denervation by SCGx in SHR attenuated local vascular remodeling, suggesting that sympathetic overactivity is a crucial pathogenic factor of vascular remodeling in SHR., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Jasmonic acid (JA) is an important phytohormone used to defend against herbivores, but it does not respond to whitefly feeding. Conversely, another phytohormone, salicylic acid (SA), is induced when plants are fed upon by whiteflies. JA has a better anti-whitefly effect than SA; however, there is limited research on how to effectively improve plant resistance by utilizing the different responses of these phytohormones to whitefly feeding., Results: We discovered that protease inhibitors 8 (PI8) and terpene synthase 10 (TPS10) located downstream of the JA-regulated pathway in plants have anti-whitefly effects, but these two genes were not induced by whitefly feeding. To identify whitefly-inducible promoters, we compared the transcriptome data of tobacco fed upon by Bemisia tabaci with the control. We focused on pathogenesis-related (PR) genes because they are known to be induced by SA. Among these PR genes, we found that expression levels of pathogenes-related protein 1C-like (PR1) and glucose endo-1,3-beta-glucosidase (BGL) can be significantly induced by whitefly feeding and regulated by SA. We then engineered the whitefly-inducible promoters of BGL and PR1 to drive the expression of PI8 and TPS10. We found that compared with control plants that did not induce the expression of PI8 or TPS10, transformed plants expressing PI8 or TPS10 under the PR1 or BGL promoter showed a significant increase in the expression levels of PI8 and TPS10 after whitefly infection, significantly improving their resistance to whiteflies., Conclusion: Our findings suggest that using SA-inducible promoters as tools to drive the expression of JA-regulated defense genes can enhance plant resistance to whiteflies. Our study provides a novel pathway for the enhancement of plant resistance against insects. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Mycotoxins are ubiquitous natural pollutants that pose a serious threat to public health. Deoxynivalenol (DON) as one of the most prominent mycotoxins has a noticeable adverse effect on intestinal barrier function, which depends on the intestinal barrier integrity. However, the potential mechanisms and effective therapeutic strategies remain unclear. Aryl hydrocarbon receptor (AHR) has been implicated in the modulation of intestinal barrier function and inflammation. The study aims to investigate the unique role of AHR in mediating DON-induced intestinal epithelial barrier function. In the current study, we revealed that DON triggered mitochondrial structural damage and functional impairment, leading to oxidative stress and apoptosis in porcine jejunal epithelial cells (IPEC-J2). DON altered the integrity of IPEC-J2 cells by disrupting the distribution and function of tight junction proteins. Additionally, DON activated TNF-α/NF-κB/MLCK signaling pathway, thereby eliciting inflammatory response. Notably, DON inhibited AHR nuclear translocation and attenuated xenobiotic response element promoter activity and its target genes. However, overexpression of AHR mitigated DON-induced disruption of intestinal epithelial barrier functions by suppressing TNF-α/NF-κB/MLCK pathway in IPEC-J2 cells. Our findings indicate that AHR regulates intestinal epithelial barrier function and therefore is a novel therapeutic molecule for intestinal disorders., 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 B.V. All rights reserved.)

The alkylation of nucleophiles is among the most fundamental and well-developed transformations in chemistry. However, to achieve selective alkylation of complex substrates remains a nontrivial task. We report herein a general and selective alkylation method without using strong acids, bases, or metals. In this method, the readily available phosphinites/phosphites, in combination with ethyl acrylate, function as effective alkylating agents. Various nucleophilic groups, including alcohols, phenols, carboxylic acids, imides, and thiols can be alkylated. This method can be applied in the late-stage alkylation of natural products and pharmaceutical agents, achieving chemo- and site-selective modification of complex substrates. Experimental studies indicate the relative reactivity of a nucleophile depends on its acidity and its steric environment. Mechanistic studies suggest the reaction pathway resembles that of the Arbuzov-Michalis reaction., (© 2024 Wiley-VCH GmbH.)

Background and Objectives: Amidst increasing opioid-related overdoses in the USA, opioid use disorder (OUD) treatment has seen few novel treatments emerge. High-potency synthetic opioids (HPSOs) have altered clinical approaches, prompting evaluation of existing medications for opioid use disorder (MOUD) and interest in slow-release oral morphine (SROM) as another therapeutic option. Here we survey addiction specialists on the influence of HPSOs on clinical practice, views on current MOUD regulations, and openness to novel therapies such as SROM., Methods: Anonymous, online survey conducted at a national conference of addiction specialists (N = 91). Pearson χ 2 tests and Fisher's exact tests to compare respondent characteristics., Results: Approximately 89% of respondents (N = 91) acknowledge that HPSOs shifted addiction treatment in recent years, with 86% modifying their MOUD prescribing accordingly. Moreover, 84% report having patients who could benefit from other full opioid agonists beyond methadone for OUD management. Many report off-label prescribing of full agonist opioids other than methadone for withdrawal symptoms or initiating MOUD. Eighty percent reported being in favor of incorporating SROM as a third-line monotherapy for OUD., Discussion and Conclusion: This sample of addiction specialists supports innovative alternatives for MOUD in the USA to combat the challenges posed by fentanyl and related HPSOs. Future work should further addiction specialists' opinions on barriers to OUD treatment and exploration of these international strategies in the USA., Scientific Significance: This appears to be the first study exploring addiction specialists' perspectives on regulatory barriers to OUD treatment and their willingness to uptake internationally adopted strategies such as SROM., (© 2024 The Author(s). The American Journal on Addictions published by Wiley Periodicals LLC on behalf of The American Academy of Addiction Psychiatry (AAAP).)

Perovskite nanocrystals are embedded into metal-organic frameworks (MOFs) to create composites with high light absorption coefficients, tunable electronic properties, high specific surface area, and metal atom tunability for enhanced photocatalytic carban dioxide (CO 2 ) reduction. However, existing perovskite-MOF structures with a large particle size are achieved based on Pb source adsorption into the pores of MOFs, which can significantly break down the porous structure, thereby resulting in a decreased specific surface area and impacting CO 2 adsorption. Herein, a novel perovskite-MOF structure based on the synthesis of bimetallic Pb-containing MOFs and post-processing to convert Pb to CsPbBr 3 nanocrystals (NCs) is proposed. It is discovered that the additional Pb is not introduced by adsorption, but instead engages in coordination and generates Pb-N. The produced ZIF-8@CsPbBr 3 NCs are ≈40 nm and have an ultra-high specific surface area of 1325.08 m 2 g -1 , and excellent photovoltaic characteristics, which are beneficial for photocatalytic CO 2 reduction. The electronic conversion rate of composites is 450 mol g -1 h -1 , which is more than three times that of pure perovskites. Additionally, the superior reduction capacity is sustained after undergoing four cycles. Density Functional Thoery (DFT) simulations are used to explore the 3D charge density at the ZIF-8@CsPbBr 3 NCs interface to better understand the electrical structure., (© 2024 Wiley‐VCH GmbH.)

Janus-micromotors, as efficient self-propelled materials, have garnered considerable attention for their potential applications in non-agitated liquids. However, the design of micromotors is still challenging and with limited approaches, especially concerning speed and mobility in complex environments. Herein, a two-step spray-drying approach encompassing symmetrical assembly and asymmetrical assembly is introduced to fabricate the metal-organic framework (MOF) Janus-micromotors with hierarchical pores. Using a spray-dryer, a symmetrical assembly is first employed to prepare macro-meso-microporous UiO-66 with intrinsic micropores (<0.5 nm) alongside mesopores (≈24 nm) and macropores (≈400 nm). Subsequent asymmetrical assembly yielded the UiO-66-Janus loaded with the reducible nanoparticles, which underwent oxidation by KMnO 4 to form MnO 2 micromotors. The micromotors efficiently generated O 2 for self-propulsion in H 2 O 2 , exhibiting ultrahigh speeds (1135 µm s -1 , in a 5% H 2 O 2 solution) and unique anti-gravity diffusion effects. In a specially designed simulated sand-water system, the micromotors traversed from the lower water to the upper water through the sand layer. In particular, the as-prepared micromotors demonstrated optimal efficiency in pollutant removal, with an adsorption kinetic coefficient exceeding five times that of the micromotors only possessing micropores and mesopores. This novel strategy fabricating Janus-micromotors shows great potential for efficient treatment in complex environments., (© 2024 Wiley‐VCH GmbH.)

The continuously increasing level of atmospheric CO 2 in the atmosphere has led to global warming. Converting CO 2 into other carbon compounds could mitigate its atmospheric levels and produce valuable products, as CO 2 also serves as a plentiful and inexpensive carbon feedstock. However, the inert nature of CO 2 poses a major challenge for its reduction. To meet the challenge, nature has evolved metalloenzymes using transition metal ions like Fe, Ni, Mo, and W, as well as electron-transfer partners for their functions. Mimicking these enzymes, artificial metalloenzymes (ArMs) have been designed using alternative protein scaffolds and various metallocofactors like Ni, Co, Re, Rh, and FeS clusters. Both the catalytic efficiency and the scope of CO 2 -reduction product of these ArMs have been improved over the past decade. This review first focuses on the natural metalloenzymes that directly reduce CO 2 by discussing their structures and active sites, as well as the proposed reaction mechanisms. It then introduces the common strategies for electrochemical, photochemical, or photoelectrochemical utilization of these native enzymes for CO 2 reduction and highlights the most recent advancements from the past five years. We also summarize principles of protein design for bio-inspired ArMs, comparing them with native enzymatic systems and outlining challenges and opportunities in enzymatic CO 2 reduction., Competing Interests: Declaration of competing interest We declare that we 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.)

Objective: Increasing breast meat production is one of the primary goals of the broiler industry. Over the past few decades, tremendous progress has been made in genetic selection and the identification of candidate genes for improving the breast muscle mass. However, the molecular network contributing to muscle production traits in chickens still needs to be further illuminated., Methods: A total of 150 1-day-old male 817 broilers were reared in a floor litter system. At the market age of 50 d, eighteen healthy 817 broilers were slaughtered and the left pectoralis major muscle sample from each bird was collected for RNA-seq sequencing. The birds were then plucked and eviscerated and the whole breast muscle was removed and weighed. Breast muscle yield was calculated as the ratio of the breast muscle weight to the eviscerated weight. To identify the co-expression networks and hub genes contributing to breast muscle yield in chickens, we performed weighted gene co-expression network analysis (WGCNA) based on the 18 transcriptome datasets of pectoralis major muscle from eighteen 817 broilers., Results: The WGCNA analysis classified all co-expressed genes in the pectoral muscle of 817 broilers into 44 modules. Among these modules, the turquoise and skyblue3 modules were found to be most significantly positively (r = 0.78, p = 1e-04) and negatively (r = -0.57, p = 0.01) associated with breast meat yield, respectively. Further analysis identified several hub genes (e.g., DLX3, SH3RF2, TPM1, CAV3, MYF6, and CFL2) that involved in muscle structure and muscle development were identified as potential regulators of breast meat production., Conclusion: The present study has advanced our understanding of the molecular regulatory networks contributing to muscle growth and breast muscle production and will contribute to the molecular breeding of chickens in the future.

To investigate the computed tomography (CT) image characteristics, adjacent tissues, and related measurement indices of the sternal foramina and provide an anatomical basis for the safety of minimally invasive sternum surgery. The data from 2500 thoracic multi-slice computed tomography (MSCT) cases from January 2020 to June 2021 were analyzed retrospectively. The number and location of the sternal foramina and adjacent tissues (mediastinal adipose tissue, lung, pericardium) were observed. The size of the sternal foramina, CT value of the tissue inside the foramina, subcutaneous adipose tissue thickness, distance from skin to lung, distance from skin to the pericardium, and manubrio-foraminal distance were measured. Sex differences were compared for each indicator performed. The incidence of sternal foramina was 4.44% (111/2500), with 83 males and 28 females. All sternal foramina were located at the mesosternum's fourth to sixth costal cartilage level. The transverse diameter of the sternal foramina was (0.60 ± 0.29) cm, and the vertical diameter was (0.68 ± 0.39) cm, which was greater in males than females (p > 0.01). The CT value of the tissue in the sternal foramina was (-77.05 ± 32.26) Hu, and there was no statistical difference between male and female patients (t = -1.780, p = 0.078). The adjacent tissues of the sternal foramina were only adjacent to adipose tissue in 41 cases (36.94%), pericardium in 18 patients (16.22%), lung tissue in 37 cases (33.33%), and both kinds of tissue in 15 cases (13.51%). The sternal foramina were not adjacent to the left lung in the female patients. In the sternal foramina region, the thickness of subcutaneous adipose tissue was (1.13 ± 0.51) cm, the distance from skin to lung was (1.86 ± 0.57) cm, the distance from skin to pericardium was (3.07 ± 0.72) cm, the manubrio-foraminal distance was (12.68 ± 1.31) cm, which was significantly greater in males than in females (p < 0.05). The sternal foramina are closely related to the heart and lungs. The size and location of sternal foramina, the thickness of subcutaneous adipose tissue, and the distance from skin to heart and lung are all crucial factors in evaluating the safety of sternal puncture biopsy., (© 2023 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

In the coastal waters around Shandong peninsula, an unprecedented winter bloom of dinoflagellates Gonyaulax polygramma and Akashiwo sanguinea occurred in 2021 from late November to early December. The bloom affected a wide area of coastal waters extending from west to east along the northern Shandong peninsula and had a devastating blow to the kelp cultivation industry. Based on the remote-sensing data, the initiation of the bloom was traced back to the region adjacent to the mouth of the Yellow River in Laizhou Bay, where enhanced freshwater discharge from the Yellow River was recorded from September to November. It's proposed that the increased precipitation in the Yellow River basin associated with northward extension of the precipitation band in China could be an important reason for this winter bloom. This unusual winter bloom around Shandong peninsula highlights the potential risks of harmful algal blooms and their impacts on coastal ecosystems under the background of climate change., 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.)

Objectives: To analyze the methodology, evidence, recommendations, quality, and implementation of traditional Chinese patent medicine (CPM) guidelines., Methods: We retrieved clinical application guidelines of CPM published from 2019 to 2022. Independent screening and data extraction were performed by two evaluators. The basic information about the guidelines, including evidence and recommendations, were extracted and statistically analyzed. Quality and implementation were evaluated using the Implementation Evaluation Tool and Appraisal of Guidelines for Research & Evaluation (AGREE) II., Results: In total, 29 guidelines were analyzed, including 262 recommendations and 2308 references. All the CPM guidelines followed the principle of "evidence as a core, consensus as a supplement, and experience as a reference" and the methods provided by WHO Handbook. An average of 89 references were cited in each guideline and 8 in each recommendation. Randomized controlled trials and systematic reviews constituted 89 % and 0.9 %, respectively, of all references. Low or very low-quality evidence characterized 74.5 % and weak recommendations characterized 83.6 %. Of all recommendations, 13.7 % were based on expert consensus, and 9.5 % of strong recommendations were based on low or very low-quality evidence. The AGREE II scores for each domain were: scope and purpose (79.63 %) and editorial independence (79.27 %), followed by clarity of presentation (72.59 %), stakeholder involvement (69.99 %), rigor of development (53.97 %) and applicability (5.11 %). The implementation quality of most guidelines was either high (44.8 %) or moderate (55.2 %)., Conclusions: The results for CPM guidelines were impressive in terms of methodology, quality, and implementation. However, confidence in CPM recommendations was downgraded by low quality of evidence., Competing Interests: Declaration of Competing Interest All the members of this guideline have signed a conflict of interest statement, stating that there was no commercial, professional, or other interest related to this guideline's topic, nor was there any interest associated with the possible impact of the outcomes of this guideline., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Passive battery thermal management systems (BTMSs) are critical for mitigation of battery thermal runaway (TR). Phase change materials (PCMs) have shown promise for mitigating transient thermal challenges. Fluid leakage and low effective thermal conductivity limit PCM adoption. Furthermore, the thermal capacitance of PCMs diminishes as their latent load is exhausted, creating an unsustainable cooling effect that is transitory. Here, an expanded graphite/PCM/graphene composite that solves these challenges is proposed. The expanded graphite/PCM phase change composite eliminates leakage and increases effective thermal conductivity while the graphene coating enables radiative cooling for PCM regeneration. The composite demonstrates excellent thermal performance in a real BTMS and shows a 26% decrease in temperature when compared to conventional BTMS materials. The composite exhibits thermal control performance comparable with active cooling, resulting in reduced cost and increased simplicity. In addition to BTMSs, this material is anticipated to have application in a plethora of engineered systems requiring stringent thermal management., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: In recent years, 5-Methoxytryptophan (5-MTP) has been identified as an endothelial factor with vaso-protective and anti-inflammatory properties., Methods: In this prospective cohort study, a total of 407 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) successfully were enrolled. A 1-year follow-up Kaplan-Meier survival analysis was used for evaluating the correlation between 5-MTP and major adverse cardiovascular event (MACE) while Cox proportional-hazards regression was used to identify predictive values of 5-MTP on MACE after AMI., Results: Increased 5-MTP level led to a significant downtrend in the incidence of MACE (All Log-rank p < 0.05). Thus, a high baseline 5-MTP could reduce the 1-year incidence of MACE (HR = 0.33, 95%Cl 0.17-0.64, p = 0.001) and heart failure (HF) (HR = 0.28, 95% Cl 0.13-0.62, p = 0.002). Subgroup analysis indicated the predictive value of 5-MTP was more significant in patients aged ≤ 65 years and those with higher baseline NT-proBNP, T2DM, STEMI, and baseline HF with preserved LVEF (HFpEF) characteristics., Conclusions: Plasma 5-MTP is an independent and protective early biomarker for 1-year MACE and HF events in patients with AMI, especially in younger patients and those with T2DM, STEMI, and baseline HFpEF characteristics., (© 2024. The Author(s).)

Objectives: To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization (MR) analysis., Methods: Bidirectional MR was used to analyze pooled data from different genome-wide association studies (GWAS). The causal effect of plasma metabolites on osteoporosis was estimated using the inverse variance weighted method, intersections of statistically significant metabolites obtained from different sources of osteoporosis-related GWAS aggregated data was determined, and then sensitivity analysis was performed on these metabolites. Heterogeneity between single nucleotide polymorphisms was evaluated by Cochran's Q test. Horizontal pleiotropy was assessed through the application of the MR-Egger intercept method and the MR-PRESSO method. The causal effect of osteoporosis on plasma metabolites was also evaluated using the inverse variance weighted method. Additionally, pathway analysis was conducted to identify potential metabolic pathways involved in the regulation of osteoporosis., Results: Primary analysis and sensitivity analysis showed that 77 and 61 plasma metabolites had a causal relationship with osteoporosis from the GWAS data in the GCST90038656 and GCST90044600 datasets, respectively. Five common metabolites were identified via intersection. X-13684 levels and the glucose-to-maltose ratio were negatively associated with osteoporosis, whereas glycoursodeoxycholate levels and arachidoylcarnitine (C20) levels were positively associated with osteoporosis (all P < 0.05). The relationship between X-11299 levels and osteoporosis showed contradictory results (all P < 0.05). Pathway analysis indicated that glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, galactose metabolism, arginine biosynthesis, and starch and sucrose metabolism pathways were participated in the development of osteoporosis., Conclusions: We found a causal relationship between plasma metabolites and osteoporosis. These results offer novel perspectives with important implications for targeted metabolite-focused interventions in the management of osteoporosis.

The stability of soil organic matter (SOM) is crucial for metal transport and carbon cycling. S,S-ethylenediaminedisuccinic acid (EDDS) is widely used to enhance phytoremediation efficiency for heavy metals in contaminated soils, yet its specific impacts on SOM have been underexplored. This study investigates the effects of EDDS on SOM stability using a rhizobox experiment with ryegrass. Changes in soil dissolved organic matter (DOM) quantity and molecular composition were analyzed via Fourier transform ion cyclotron resonance mass spectrometry. Results showed that the use of EDDS increased the uptake of Cu, Cd and Pb by ryegrass, but simultaneously induced the destabilization and transformation of SOM. After 7 days of EDDS application, dissolved organic carbon (DOC) and nitrogen (DON) concentrations in rhizosphere soils increased significantly by 3.44 and 10.2 times, respectively. In addition, EDDS reduced lipids (56.3%) and proteins/amino sugars-like compounds (52.1%), while increasing tannins (9.11%) and condensed aromatics-like compounds (24.4%) in the rhizosphere DOM. These effects likely stem from EDDS's dual action: extracting Fe/Al from SOM-mineral aggregates, releasing SOM into the DOM pool, and promoting microbial degradation of bioavailable carbon through chain scission and dehydration. Our study firstly revealed that the application of EDDS in phytoremediation increased the mineralization of SOM and release of CO 2 from soil to the atmosphere, which is important to assess the carbon budget of phytoremediation and develop climate-smart strategy in future., 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.)

The neural crest generates numerous cell types, but conflicting results leave developmental origins unresolved. Here using somatic mosaic variants as cellular barcodes, we infer embryonic clonal dynamics of trunk neural crest, focusing on the sensory and sympathetic ganglia. From three independent adult neurotypical human donors, we identified 1,278 mosaic variants using deep whole-genome sequencing, then profiled allelic fractions in 187 anatomically dissected ganglia. We found a massive rostrocaudal spread of progenitor clones specific to sensory or sympathetic ganglia, which unlike in the brain, showed robust bilateral distributions. Computational modeling suggested neural crest progenitor fate specification preceded delamination from neural tube. Single-cell multiomic analysis suggested both neurons and glia contributed to the rostrocaudal clonal organization. CRISPR barcoding in mice and live imaging in quail embryos confirmed these clonal dynamics across multiple somite levels. Our findings reveal an evolutionarily conserved clonal spread of cells populating peripheral neural ganglia.