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Shuai Tang,1– 4 Wenyu Feng,2– 4 Zekun Li,1 Xinjuan Liu,1 Tong Yang,1– 4 Fulan Wei,2– 4 Gang Ding1 1School of Stomatology, Shandong Second Medical University, Weifang, Shandong, 261053, People’s Republic of China; 2Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Shandong Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 4Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Gang Ding, School of Stomatology, Shandong Second Medical University, Baotong West Street No. 7166, Weifang, Shandong, 261053, People’s Republic of China, Email dinggang@sdsmu.edu.cn Fulan Wei, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Wenhua West Road No. 44-1, Jinan, Shandong, 250012, People’s Republic of China, Email weifl@sdu.edu.cnIntroduction: Inflammatory bowel disease is a complex chronic inflammatory condition characterized by dysbiosis of the gut microbiota and dysregulation of immune system. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells have garnered significant attention for their beneficial potentials in immune modulation and tissue repair. This study aims to evaluate the therapeutic effects and underlying mechanisms of EVs derived from lipopolysaccharide (LPS)-pretreated periodontal ligament stem cells (PDLSCs) in mice with colitis.Methods: A mouse model of colitis was established using 3.0% dextran sulfate sodium (DSS). Following the induction of colitis, mice were treated via tail vein injection with either conventional PDLSC-derived EVs (P-EVs) or LPS-pretreated PDLSC-derived EVs (LPS pre-EVs). The EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. The therapeutic effects and mechanisms were evaluated through a combination of small animal live imaging, disease activity index (DAI) scoring, histopathological staining, qRT-PCR, 16S rRNA gene sequencing, and mass spectrometry analysis.Results: The LPS pre-EVs exhibited typical EVs characteristics in terms of morphology, particle size distribution, and marker protein expression. Compared to P-EVs, LPS pre-EVs significantly ameliorated weight loss, DAI scores, colon length, and perianal symptoms in DSS-induced murine colitis. Additionally, LPS pre-EVs up-regulated the expression of Arginase-1, a typical M2 macrophage marker, and tight junction proteins, including ZO-1, Occludin, and Claudin-1, enhanced gut microbial diversity, and significantly regulated intestinal protein expression and activation of the PI3K/AKT signaling pathway.Conclusion: LPS pre-EVs exhibit significant anti-inflammatory and tissue repair effects in a mouse model of colitis. The underlying mechanisms may involve the regulation of macrophage polarization, maintenance of intestinal barrier function, modulation of the gut microbiota, and activation of the PI3K/AKT signaling pathway. Keywords: inflammatory bowel disease, periodontal ligament stem cells, extracellular vesicles, gut microbiota, PI3K/AKT signaling pathway

Identifying the diverse roles of disorderly packed atoms inside an amorphous solid has been a highly pursued but daunting task in glass physics. By analyzing the full-frequency vibrational modes of a model Cu50Zr50 glass, here, we classify the internal atoms into low-, subhigh-, and high-frequency ones that have different tendencies for rearrangements upon excitations. We find that low-frequency atoms are structurally unfavored and tend to aggregate. High-frequency atoms originating from compressed atomic pairs are also mechanically unstable. As yield approaches, shear-transformation rearrangements shift from low-frequency to high-frequency atoms. Subhigh-frequency atoms play the role of stable backbones. Given that atoms can have different identities, multiple identities are observed to overlap in space. Atoms with one vibrational identity often transform to another one, showing different preferences in transformation routes. Our results deepen the understanding of atomic structures for amorphous plasticity beyond the simplified picture of soft vs hard spots. [ABSTRACT FROM AUTHOR]

Geosynthetics are widely used in soil reinforcement engineering, the failure modes of which are typically pullout modes. However, current research on monitoring the pullout damage experienced by reinforced soil is limited. Accordingly, in this study, the stress variation laws and signal output characteristics of a sensor-enabled piezoelectric geobelt (SPGB) that can capture the tensile vibration signals of reinforced soil under various tensile failure conditions were examined. It was found that the SPGB captured the response signals under different soil environments, confining pressures, and shear rates. During the pullout friction process, a spike was generated, and the displacement corresponding to the position of the spike increased with an increase of the pullout friction rate. In the clay environment, the spike voltage was related to the confining pressure, while in the sand environment, there was no obvious relationship between the spike voltage and the confining pressure. In the gravel environment, the output voltage of the SPGB fluctuated greatly, due to the embedment of gravel particles, and many negative voltages of large amplitude appeared. The results of this study verify the promising application potential of SPGBs for the integration of soil reinforcement and monitoring, which is significant for further applications of SPGBs in engineering. [ABSTRACT FROM AUTHOR]

Huan Tang, Wenjuan Di, Hanmei Qi, Juan Liu, Jing Yu, Jinmei Cai, Bing Lai, Guoxian Ding, Peng Cheng Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Peng Cheng, Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People’s Republic of China, Tel +86-25-68305171, Fax +86-25-83724440, Email cphh@sohu.comPurpose: This study was designed to explore age-related changes in trabecular bone score (TBS) and bone mineral density (BMD) in Chinese men through cross-sectional and longitudinal studies.Patients and Methods: We included adult men who had at least twice TBS and BMD examinations in our hospital between January 2013 and December 2020. All men were divided into an age subgroup per 10 years, comparing differences in baseline lumbar spine (LS) TBS and BMD at various parts between each age group and analyzing age-related changes in TBS and BMD during follow-up.Results: Baseline data showed that in men aged 36 to 85 years, BMD in the hip region showed a decreasing trend with age (P for trend < 0.01). However, TBS reached a high value around the age of 50, after which it decreased with age (P for trend = 0.03). During a mean follow-up of 3 years, the average annual change rate at TBS was − 0.17% in men aged 36 to 85 years, with the fastest decrease rate − 1.08% at 66 to 75 years (P < 0.05). The mean annual rate of change in LS BMD in different age subgroups increased with age (P for trend = 0.001). There was no significant decrease in mean annual change in BMD in hip regions.Conclusion: In men aged 36∼ 85 years, the trend of TBS was inconsistent with BMD. Men experience a high value of LS TBS around age 50, later than the commonly believed age of peak BMD, which may reflect developmental differences between bone microstructure and bone minerals. The TBS may be used as a better indicator of changes in bone strength than BMD in adult men at short-term follow-up. The rapid loss of TBS at age 66 to 75 may have implications for the prevention and medication of osteoporosis in men.Keywords: age-related, bone loss, bone mineral density, men, osteoporosis, trabecular bone score

Sirui Song,1 Liqin Chen,1 Qianqian Ning,2 Danying Zhu,1 Feng Qiu,2 Guang Li,2 Hong Zhang,3 Tingting Xiao,1 Guohui Ding,4 Min Huang1 1Department of Cardiology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Shanghai Center for Bioinformation Technology, Shanghai, People’s Republic of China; 3Department of Laboratory, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4International Human Phenome Institutes, Shanghai, 200235, People’s Republic of ChinaCorrespondence: Min HuangDepartment of Cardiology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Email huangmin@sjtu.edu.cnGuohui DingInternational Human Phenome Institutes, Shanghai, 200235, People’s Republic of China, Email dingguohui@ihup.org.cnPurpose: Kawasaki disease (KD) is an acute systemic vasculitis mainly found in the medium-sized arteries, especially the coronary arteries. Immune system is involved in the pathogenesis of acute KD in children, but the functional differences in the immune system between healthy children and KD patients remain unclear.Patients and Methods: A total of 190 KD patients and 119 healthy controls were recruited for the next-generation sequencing of 512 targeted genes from 4 immune-related pathways. Subsequently, the peripheral blood mononuclear cells (PBMCs) were isolated. RNA sequencing of the LPS treated PBMCs from additional 20 KD patients and 20 healthy controls was used to examine the differentially expressed genes (DEGs). Then, an expression quantitative trait locus (eQTL) analysis combined with previously analyzed RNA data were used to examine the DEGs. Finally, the serum levels of 13 cytokines were detected before and after LPS treatment in 40 samples to confirm the findings from eQTL analysis.Results: A total of 319 significant eQTL were found, and both eQTL analysis and RNA sequencing showed some DEGs were involved in the connective tissue disorders and inflammatory diseases. DEGs that function to negatively regulate immunity were closely related to the pathogenesis of KD. In addition, the serum levels of IL-10 (an inflammatory and immunosuppressive factor) and SCD25 (an important immunosuppressant) reduced significantly in the KD patients.Conclusion: Our study shows the expression of factors responsible for the negative control of innate immunity is altered, which plays an important role in the etiology of KD.Keywords: Kawasaki disease, innate immunity, inflammation, next generation sequencing, cytokines

Lei Jin,1,&ast; Xuemei Ma,2,&ast; Nan Zhang,3 Qian Zhang,4 Xueming Chen,1 Zhongtao Zhang,2 Guoqian Ding,2 Hongzhi Yu1 1Department of Vascular Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Radiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Clinical Epidemiology and EBM Center, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhi Yu; Guoqian Ding Email HongzYu@yeah.net; dingguoqiandgq@yeah.netPurpose: This study aimed to explore the value of miR-181a-2-3p in cisplatin (DDP) treatment effectiveness prediction, and to reveal the function underlying the reversal of DDP resistance in patients with gastric cancer (GC).Methods: miRNA expression dataset of three DDP-resistant GC cell lines and their DDP-sensitive parental cell lines obtained from GEO DataSets and GenBank, and functional miRNAs were annotated by bioinformatics analyses. Serum specimens and tumor samples were collected from 91 GC patients for understanding of the interrelation between chemotherapy response and miRNA expression. RT-qPCR validated these miRNAs at the transcriptional level in both gastric cancer cells and 91 gastric cancer patients. The correlation between the miRNAs expression and clinical parameters of the patients were analyzed. Receiver operating characteristics (ROC) analysis has been utilized to assess the diagnostic performance. The MTT and colony formation assays were performed to assess cell proliferation. Flow cytometry was conducted to detect cell apoptosis. DDP-resistant GC cells and their DDP-sensitive parental cells were transfected with miRNA mimic or inhibitor vector to overexpress or downregulate miRNA expression.Results: miR-181a-2-3p as a unique miRNA was found in the common differentially expressed-miRNAs (DE-miRNAs) after miRNA screening and validation from three DDP-resistant and DDP-sensitive gastric cancer cell lines. Clinical data analysis displayed that miR-181a-2-3p expression was apparently increased in larger tumor size (≥ 5 cm), higher T stage (T4), and chemotherapy resistance. miR-181a-2-3p (AUC=0.926, SE=0.028, 95% CI: 0.872– 0.980, p< 0.0001) differentiated chemosensitive GC patients from chemoresistant GC patients. miR-181a-2-3p presented a higher level in gastric cancer, and could serve as a valid biomarker to predict the overall survival of GC patients. Upregulation of miR-181a-2-3p rendered the apoptosis-inducing and anti-proliferative effects of DDP, while downregulating it decreased these effects.Conclusion: miR-181a-2-3p can function as a therapeutic target and a tumor biomarker. Targeting oncogenic miR-181a-2-3p inhibits growth and suppresses cisplatin resistance of gastric cancer.Keywords: biomarker, miR-181a-2-3p, cisplatin resistance, gastric cancer, bioinformatic analysis

Yi Wang,1 Wenhua Li,1 Hongmei Zhang,1 Qingfeng Zhang,1 Geqi Ding,1 Zhiyu Guo,2 Yan Deng,1 Chunmei Li,1 Lixue Yin1 1Key Laboratory of Ultrasound in Cardiac Electrophysiology and Biomechanics of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2GE Cardiovascular Ultrasound Clinical & Research Department, Chengdu, People’s Republic of ChinaCorrespondence: Lixue YinKey Laboratory of Ultrasound in Cardiac Electrophysiology and Biomechanics of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, 32#, Xierduan, 1st Ring Road, Chengdu, People’s Republic of ChinaTel +86 18981838968Email yinlixue_cardiac@163.com; yinlixue8968@126.comPurpose: Left ventricular (LV) contractile reserve is commonly used for LV systolic function assessment, while data on normal LV contractile reserve to exercise and the effect of gender on it are contradictory and limited, especially in Chinese adults. The aims of the present study are to clarify echocardiographic normal reference of LV contractile reserve during treadmill exercise stress echocardiography in healthy Chinese adults and to evaluate the sex-specific impact on it.Patients and Methods: The study population consisted of 157 healthy Chinese adults. All subjects underwent comprehensive echocardiographic assessment at rest and immediately after a symptom-limited treadmill stress test. The impact of gender on LV contractile reserve was analyzed.Results: The study population consisted of 157 healthy Chinese adults. All subjects underwent comprehensive echocardiographic assessment at rest and immediately after a symptom-limited treadmill stress test. The impact of gender on LV contractile reserve was analyzed.Conclusion: Traditional LV contractile reserve of men was much higher than that of women in a healthy Chinese population. The difference might be because of higher BSA in men. ΔGLS was less influenced by METs and CI at rest compared to ΔEF. ΔGLS, and especially the ΔGLS index, might be considered as a more preferable contractile reserve parameter for clinical cardiac function evaluation.Keywords: stress echocardiography, treadmill stress test, left ventricular contractile reserve, longitudinal strain

Huashan Li,1,* Jianying Sheng,1,* Jing Wang,1 Haiting Gao,1 Jing Yu,2 Guoxian Ding,2 Ning Ding,1 Weiqi He,1,3 Juanmin Zha1 1Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Suda (CAM-SU) Genomic Resource Center, Medical College of Soochow University, Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Geriatrics, Division of Geriatric Endocrinology, The First Affiliated Hospital to Nanjing Medical University, Nanjing, People’s Republic of China; 3State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiqi He; Juanmin ZhaCambridge-Suda (CAM-SU) Genomic Resource Center, Medical College of Soochow University, Department of Oncology, The First Affiliated Hospital of Soochow University, 199 Ren-Ai Road, Suzhou, 205123, People’s Republic of ChinaTel +86-512-6588-3545Fax +86-6588-3562Email whe@suda.edu.cn; zhajuanmin@suda.edu.cnIntroduction: The effect of 11β-hydroxysteroid dehydrogenase type1 (11β-HSD1) inhibition on hepatic steatosis is incompletely understood. Here, we aimed to determine the therapeutic effect of BVT.2733, a selective 11β-HSD1 inhibitor, on hepatic steatosis.Materials and Methods: C57B/6J mice were randomly divided into a low-fat diet (LFD) fed group and a high-fat diet (HFD) fed group. Mice were fed with HFD for 28 weeks which induced obesity and severe hepatic steatosis. The two groups were further divided into four groups as follows: LFD, LFD with BVT.2733, HFD, and HFD with BVT.2733. Mice in LFD+BVT and HFD+BVT groups were intraperitoneally injected with BVT.2733 daily for 30 days. Effects of BVT.2733 on mice body weight, serum lipid profile, serum free fatty acids (FFAs), glucocorticoid levels, gene expression in adipose and liver tissues were assessed.Results: Injection of a low dose of BVT.2733 (50 mg/kg/day) reduced body weight and hyperlipidemia, but did not improve glucose tolerance and insulin resistance in diet-induced obese mice. The low dose of BVT.2733 attenuated hepatic steatosis, liver injury, and liver lipolytic gene expression in diet-induced obese mice. Besides, the low dose of BVT.2733 reduced fat mass and lipolysis in visceral adipose tissues, hepatic FFAs, and serum corticosterone levels in diet-induced obese mice.Conclusion: Our study shows that moderate inhibition of 11β-HSD1 by BVT.2733 reduces FFAs and corticosterone synthesis in fatty tissues, thereby attenuates the delivery of corticosterone and FFAs to the liver. Collectively, this prevents high-fat diet-induced hepatic steatosis.Keywords: 11β-HSD1, hepatic steatosis, inhibitor, adipose tissue, free fatty acids

In this study, a sensor-enabled piezoelectric geobelt (SPGB) was developed and its mechanical properties and signal output mode were analysed. It is found that the output voltage signal of SPGB increases with the increase of strain rate. Furthermore, the normalised impedance of SPGB samples at different strain rates has a linear relationship with their strain rate. This study shows that the self-sensing function of SPGB can monitor its deformation signal and quantify its deformation behaviour. Thus, this function can provide an early warning and has a reference significance for further engineering applications of SPGB. [ABSTRACT FROM AUTHOR]

Sheng Cheng, Qiming Zheng, Guoqing Ding, Gonghui LiDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaPurpose: The clinical impacts of serum lipid levels on prostate cancer recurrence after radical prostatectomy have been evaluated by several observational studies with conflicting results. We performed the present meta-analysis to summarize the evidence evaluating the role of serum lipid profile in prostate cancer patients.Methods: We comprehensively searched the PubMed database for potentially relevant studies through January 2019. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) for the highest versus the lowest level of serum lipid levels were calculated with the DerSimonian and Laird random-effects model.Results: A total of 12 eligible studies with 10,978 prostate cancer cases were included in this study. The pooled HRs of prostate cancer recurrence after racial prostatectomy were 0.92 (95% CI 0.73–1.16, P=0.462), 0.87 (95% CI 0.56–1.35, P=0.535), 1.09 (95% CI 0.92–1.30, P=0.320), and 1.01 (95% CI 0.78–1.31, P=0.938) for serum total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride, respectively. Sensitivity analysis was conducted by excluding each study sequentially and the results showed that all the summary risk estimates were stable and not influenced by any single study.Conclusion: The present meta-analysis indicated that serum lipid levels in patients undergoing radical prostatectomy were not associated with prostate cancer recurrence.Keywords: serum lipids, prostate cancer, recurrence, radical prostatectomy, meta-analysis

Siping Zhu,1,* Wei Lin,1,* Shu Chen,1,* Hanmei Qi,1 Siting Wang,2 Aisen Zhang,1 Jinmei Cai,1 Bing Lai,1 Yunlu Sheng,1 Guoxian Ding11Division of Geriatric Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Division of Intensive Care Unit, Nanjing Jiangning Hospital, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workBackground: Sarcopenia is typically defined as the loss of muscle mass, strength and low physical performance with aging. Ultrasound is a safe and easy method for evaluating muscle mass and quality by muscle thickness (MT) and pennation angle (PA), respectively. Although the positive correlations between MT and muscle mass and handgrip strength were observed, the relationship between MT, PA and physical performance remains unclear.Purpose: This study aimed to investigate the correlation of aforementioned ultrasound parameters with muscle mass, muscle strength and physical performance and explore the utility of ultrasound in predicting sarcopenia.Patients and methods: A total of 265 elderly Chinese community dwellers were included. MT of both forearm and lower leg as well as PA of gastrocnemius was assessed by ultrasound. Muscle mass was assessed by dual-energy X-ray absorptiometry. Muscle strength was measured by a Jamar hand dynamometer. Physical performance was assessed by the Short Physical Performance Battery (SPPB).Results: Anterior radial MT in men and regional MTs except posterior fibula in women were negatively correlated with the age. No significant correlation was observed between PA and the age in both genders. Posterior tibial MT and posterior fibula MT were positively correlated with the relative appendicular skeletal muscle mass in men and women, respectively. Anterior ulnar MT was positively correlated with grip strength in both genders. Moreover, gastrocnemius medialis PA showed a positive association with gait speed and SPPB in women but not in men.Conclusion: A combination of posterior fibula MT, anterior ulnar MT and gastrocnemius medialis PA measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly women. In addition, a combination of posterior tibial MT and anterior ulnar MT measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly men.Keywords: B-mode ultrasound, muscle thickness, pennation angle, muscle mass, muscle strength, physical performance