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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.

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: 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.