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Siyan Pang,1,2 Chenchen Geng,1,2 Zihan Fan,2 Min Hou,1,3 Huilan Mao,1,2 Shuang Tao,1,4 Jing Wang,1,4 Yulun Wu,1,2 Ke Wei,1,4 Yunhao Li,1,2 Liuyang Yan,1,2 Qingling Yang,1,4,5 Changjie Chen,1,4,5 Wenrui Wang1,2,6 1Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical University, Anhui, People’s Republic of China; 2Department of Life Sciences, Bengbu Medical University, Anhui, People’s Republic of China; 3School of Basic Courses, Bengbu Medical University, Anhui, People’s Republic of China; 4Clinical Testing and Diagnose Experimental Center, Bengbu Medical University, Anhui, People’s Republic of China; 5Department of Biochemistry and Molecular Biology, Bengbu Medical University, Anhui, People’s Republic of China; 6Department of Biotechnology, Bengbu Medical University, Anhui, People’s Republic of ChinaCorrespondence: Wenrui Wang; Changjie Chen, Anhui Province Key Laboratory of Cancer Translational Medicine, Bengbu Medical University, 2600 Donghai Avenue, Bengbu, Anhui, 233030, People’s Republic of China, Email wenrui-wang1983@163.com; tochenchangjie@163.comBackground: Breast cancer is the most common cancer in women and one of the leading causes of cancer death worldwide. Ferroptosis, a promising mechanism of killing cancer cells, has become a research hotspot in cancer therapy. Simvastatin (SIM), as a potential new anti-breast cancer drug, has been shown to cause ferroptosis of cancer cells and inhibit breast cancer metastasis and recurrence. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy.Methods: In this paper, iron base form of layered double hydroxide supported simvastatin (LDHs-SIM) was synthesized by hydrothermal co-precipitation method. The characterization of LDHs-SIM were assessed by various analytical techniques, including ultraviolet-visible (UV-vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). Biological activity, ferroptosis mechanism and biocompatibility were analyzed through in vivo and in vitro analysis, so as to evaluate its therapeutic effect on breast cancer.Results: The constructed LDHs-SIM nanosystem can not only release SIM through mevalonate (MVA) pathway, inhibit the expression of glutathione peroxidase 4 (GPX4), inhibit the expression of SLC7A11 and reduce the synthesis efficiency of GSH, but also promote the accumulation of Fe2+ in cells through the release of Fe3+, and increase the intracellular ROS content. In addition, LDHs-SIM nanosystem can induce apoptosis of breast cancer cells to a certain extent, and achieve the synergistic effect of apoptosis and ferroptosis.Conclusion: In the present study, we demonstrated that nanoparticles of layered double hydroxides (LDHs) loaded with simvastatin were more effective than a free drug at inhibiting breast cancer cell growth, In addition, superior anticancer therapeutic effects were achieved with little systemic toxicity, indicating that LDHs-SIM could serve as a safe and high-performance platform for ferroptosis−apoptosis combined anticancer therapy.Keywords: layered double hydroxides, apoptosis, ferroptosis, simvastatin, breast cancer

Jianting Li,1,2 Zhenhua Dong,2 Xiaoli Wang,2 Xin Wang,2 Lulu Wang,2 Shuguang Pang1– 3 1Department of Endocrinology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, People’s Republic of China; 2Department of Endocrinology, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, People’s Republic of China; 3Department of Clinical Medicine, Weifang Medical College, Weifang Medical College, Weifang, People’s Republic of ChinaCorrespondence: Shuguang Pang, Email shuguangpang@163.comBackground and Aim: Controlling the risk factors was the most effective strategy to prevent diabetic retinopathy (DR). This study aimed to recognize the risk factors of DR, and explores whether the effect of those factors is modified by diabetes mellitus (DM) duration.Methods: A total of 1058 DM patients with information about DR assessment were included. DR was measured by a complete ophthalmic examination and was classified as having one or more distinct microaneurysms in the eyes. Data from the lab and clinical factors were gathered. Multivariate logistic analysis was used to examine the risk factors, and the best-fitting model was selected by a backward stepwise based on A1C.Results: In the current study, 274 (25.9%) patients developed DR. In the entire subjects, baseline age, the level of C-peptide, and urinary creatinine were all presented as protective effects of DR, whose odds ratios (ORs) and 95% confidence intervals (CIs) were 0.79 (0.62, 0.99), 0.75 (0.61, 0.91), and 0.70 (0.52, 0.93), respectively. Conversely, systolic pressure (SBP), urinary albumin, and BUN/Cr ratio were the important risk factors for DR with ORs (95% CIs) 1.21 (1.01, 1.46), 1.55 (1.30, 1.84), and 1.33 (1.11, 1.59), respectively. In stratification analysis, females with higher SBP would be more likely to develop DR in the short-duration group, while C-peptide and urinary creatinine showed protective effects in the long-duration group. BUN/Cr ratio all presented as a risk factor, with ORs 1.38 (p = 0.041) and 1.33 (p = 0.014) in short- and long-duration groups, respectively.Conclusion: Although renal functions presented a significant association with DR in all DM patients, the risk factors of DR varied widely in different disease-duration subjects. Target strategies to prevent DR should be put forward individually, considering the patient’s DM duration. Improving the BUN/Cr ratio may be beneficial to delaying DR.Keywords: diabetic retinopathy, clinical factors, C-peptide, BUN/Cr ratio, risk factors analyses

Qinglin Ye,&ast; Guiling Xu,&ast; Haizhen Huang,&ast; Shuting Pang, Boji Xie, Bingmei Feng, Peng Liang, Yijie Qin, Siji Li, Yin Luo, Chao Xue, Wei Li Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Chao Xue, Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email liwei030514@126.com; xccqh@126.comPurpose: Chronic kidney disease (CKD) progression is complex. There are not standardized methods for predicting the prognosis of CKD. Nicotinamide N-methyltransferase (NNMT) has been shown to be associated with renal fibrosis. This study aimed to validate NNMT as a prognostic biomarker of progressive CKD.Patients and Methods: We explored the relationship between NNMT expression and CKD-related outcome variables using the NephroseqV5 and GEO databases. Additionally, a validation set of 37 CKD patients was enrolled to measure the correlation between NNMT expression levels and CKD outcomes. Furthermore, single-cell RNA sequencing data and the Human Protein Atlas were reanalyzed to investigate the expression specificity of NNMT in the kidney. Finally, to detect the status of NNMT expression with tubular fibrosis in vivo, we constructed a unilateral ureteral obstruction (UUO) mouse treated with an NNMT inhibitor.Results: Analyzing the datasets showed that NNMT was expressed mainly in proximal tubule compartments. And patients with high NNMT expression levels had a significantly lower overall survival rate compared to those with low NNMT expression levels (P = 0.013). NNMT was independent of prognosis factors in the multivariate Cox regression model, and the AUCs for CKD progression at 1, 3, and 5 years were 0.849, 0.775, and 0.877, respectively. Pathway enrichment analysis indicated that NNMT regulates the biological processes of tubulointerstitial fibrosis (TIF). In the validation group, NNMT levels were significantly higher in the CKD group combined with interstitial fibrosis. In vivo, NNMT was a high expression in the UUO group, peaking at postoperative day 21. Treatment with an NNMT inhibitor improved renal tubular interstitial fibrosis, and expression levels of FN, α-SMA, VIM, and TGF-β 1 were decreased compared with UUO (P < 0.05).Conclusion: NNMT was expressed mainly in tubular renal compartments, and associated with CKD prognosis. It holds potential as a diagnostic biomarker for tubular fibrosis in CKD.Graphical Abstract: Keywords: nicotinamide N-methyl transferase, tubular fibrosis, chronic kidney disease, biomarker diagnosis

Na Ta,1,2 Jingchuan Mi,2 Xiaoyan Li,2 Wei Guo,2 Gaowa Yu,3 Guojun Li,4 Shuchun Pang,5 Wuyun Bai,6 Qingjie Liu,7 Haijun Zhao,8 Guangjun Wei,9 Mengguang Fan,2 Yongjun Wen1 1School of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, People’s Republic of China; 2Inner Mongolia Center for Disease Control and Research, Hohhot, People’s Republic of China; 3Tong Liao Center for Endemic Disease Control and Research, Tong Liao, People’s Republic of China; 4Chi Feng Center for Disease Control and Research, Chi Feng, People’s Republic of China; 5Xingan Meng Center for Disease Control and Research, Xingan Meng, People’s Republic of China; 6Keyouqian QI Center for Disease Control and Research, Xingan Meng, People’s Republic of China; 7Zhalute Qi Center for Disease Control and Research, Chi Feng, People’s Republic of China; 8Alukerqin Qi Center for Disease Control and Research, Chifeng, People’s Republic of China; 9Balinzuo Qi Center for Disease Control and Research, Chi Feng, People’s Republic of ChinaCorrespondence: Yongjun Wen, School of Veterinary Medicine, Inner Mongolia Agricultural University, No. 306, Zhaowuda Road, Saihan District, Hohhot, 010018, Inner Mongolia, People’s Republic of China, Email wenyongjun2022@163.comObjective: To investigate the distribution, epidemiology, and clinical symptoms of brucellosis and Q fever in northeastern Inner Mongolia.Methods: In this study, 64 townships of Bairin left flag and Alukerqin flag, Jarud flag and Horqin right front flag in four counties with frequent brucellosis and Q fever were selected. Epidemiological characteristics, clinical features, and exposure to risk factors were identified and descriptively analyzed in patients from these areas.Results: There were 367 brucellosis cases in the four regions and 78 positive cases of Q-fever infection. In addition, 24 cases of brucellosis and Q-fever co-infection were identified, with a co-infection rate of 1.13%. Brucellosis and Q fever were mainly concentrated in the 30– 65 and 40– 55 age groups. For brucellosis, the difference between age groups was statistically significant (χ2 = 29.121, P < 0.05). The sex distribution for brucellosis was 225 men (61.31%) and 142 women (38.69%), and 45 men (57.69%) and 33 women (42.31%) had Q fever. Those with brucellosis and Q fever were mainly farmers, accounting for 79.19% and 78.38% of the total number, respectively. Of the 367 cases of brucellosis infection, the main symptoms were joint pain (52.59%), fatigue (47.14%), lower back pain (38.96%), fever (33.24%), hyperhidrosis (28.88%), and muscle pain (20.44%). Of the 78 cases of Q-fever infection, the main symptoms were joint pain (35.90%), fatigue (30.77%), lower back pain (26.92%), fever (21.79%), and hyperhidrosis (17.95%). Muscle pain also accounted for 12.82%.Conclusion: Occupational distribution suggests that we should strengthen the protection measures against diseases infected through animal husbandry. Among the clinical symptoms, fever, hyperhidrosis and fatigue were associated with brucellosis, while fever, headache, and fatigue were significantly associated with Q fever.Keywords: distribution, clinical characteristics, brucellosis, Q fever, northeastern Inner Mongolia

Zhuohui Luo,1 Yongcheng Wang,2 Shuo Pang,1 Shan Gao,1 Ning Liu,1 Xiang Gao,1 Li Zhang,1,3 Xiaolong Qi,1,3 Yajun Yang,2 Lianfeng Zhang1,3 1Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100021, People’s Republic of China; 2Beijing Key Laboratory of Active Substance Discovery and Drug Ability Evaluation, Institute of Material Medical, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100050, People’s Republic of China; 3Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of ChinaCorrespondence: Yajun Yang, Institute of Material Medical, Peking Union Medical College, Chinese Academy of Medical Sciences, Nanwei Road, Xicheng District, Beijing, 100050, People’s Republic of China, Email yangyajun@imm.ac.cn Lianfeng Zhang, Institute of Laboratory Animal Science, Peking Union Medical College, Chinese Academy of Medical Sciences, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People’s Republic of China, Tel +86 10-87778442, Fax +86 10-67776394, Email zhanglf@cnilas.orgAim: Alzheimer’s disease (AD) is the most common neurodegenerative disease whose patients suffered from cognitive impairments. In our study, a novel 1,2,4-Oxadiazole derivative wyc-7-20 was synthesized, which showed low cytotoxicity and potent neuroprotective effect at the cellular level. Improved cognitive impairments, β-amyloid (Aβ) clearance, and tau pathological phenotypes were detected in transgenic animal models after wyc-7-20 treatment. Reversed expressions in AD-related genes were also detected. The results demonstrated wyc-7-20 was potent in AD therapy.Purpose: The pathological complexity of AD increased difficulties in medical research. To explore a new potential medical treatment for AD, a novel 1,2,4-Oxadiazole derivative (wyc-7-20) was designed, synthesized to explore the application in this study.Materials and Methods: Human neuroblastoma (SH-SY5Y) cells and human hepatocellular carcinoma (HepG2) cells were used to detect median lethal dose (LD50). H2O2 and Aβ1– 42 oligomers (AβOs) were respectively, added into SH-SY5Y cells to detect anti-ROS (reactive oxygen species) and anti-AβOs effects of wyc-7-20. 3×Tg mice were administered with wyc-7-20, and then Y maze test and Morris water maze (MWM) test were applied to detect cognitive improvements. Brain tissue samples were subsequently collected and analyzed using different techniques.Results: wyc-7-20 showed low cytotoxicity and potent neuroprotective effect at the cellular level. Improved cognitive impairments, Aβ clearance, and tau pathological phenotypes were detected in transgenic animal models after wyc-7-20 treatment. Reversed expressions in AD-related genes were also detected.Conclusion: wyc-7-20 was potent in AD therapy.Graphical abstract: Keywords: 1,2,4-oxadiazole, Alzheimer’s disease, animal model, neuroprotective effect

Jiang-Tao Zhang,1 Jun Chen,2 Hui-Chao Ruan,1 Feng-Xi Li,3 Sen Pang,1 Yu-Ju Xu,1 Dao-Lai Huang,1 Xiang-Hua Wu1 1Department of Gastrointestinal and Gland Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Gastrointestinal Surgery, Guangxi International Zhuang Medicine Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Xiang-Hua WuDepartment of Gastrointestinal and Gland Surgery, First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Qingxiu District, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaTel +86 771-5356701Fax +86-771-5350031Email wuxianghuag@163.comObjective: Although chemotherapy is one of the first line clinical treatment of tumors, the efficacy of chemotherapy has been severely restricted by the frequent occurrence of drug resistance phenomenon. Multiple studies found that miRNAs can regulate the chemosensitivity of tumor cells. Here, this study aimed to assess the potential role of the miR-15a-5p/cell division cycle-related protein 4 (CDCA4) axis in breast cancer (BC) resistance to Adriamycin.Methods: In the present study, the relative expression of miRNA-15a-5p in MCF-7/ADR, MCF-7 and Hs578Bst was measured by qRT-PCR. MCF-7/ADR cells underwent transfection with an miR-15a-5p mimic and inhibitor, respectively. Transwell assays, flow cytometry and CCK8 were performed to examine the potential effects of the abnormal expression of miR-15a-5p. The association of aberrant miR-15a-5p expression with Adriamycin resistance in BC was determined in cultured MCF-7/ADR cells. Bioinformatics was employed to predict the genes targeted by miR-15a-5p. Moreover, the correlation between miR-15a-5p and its target gene, CDCA4, was evaluated based on qRT-PCR data.Results: The expression of miR-15a-5p was significantly downregulated in MCF/ADR cells compared with MCF-7 and Hs578Bst cell lines. In the presence of Adriamycin, miR-15a-5p overexpression significantly increased cell chemosensitivity, as well as MCF-7/ADR cell proliferation, invasion, and migration, while promoting apoptosis and inducing cell-cycle arrest in the synthesis phase. CDCA4 RNA interference enhanced these effects as shown in our previous study. Bioinformatics identified CDCA4 as an miR-15a-5p target gene. qRT-PCR further demonstrated that CDCA4 and miR-15a-5p expression levels were inversely correlated.Conclusion: Adriamycin resistance in BC cells was, at least in part, altered by mRNA-15a-5p via regulation of its target gene, CDCA4, by controlling the cell cycle, which may provide some novel ideas for BC chemotherapy in the future.Keywords: breast cancer, Adriamycin resistance, miR-15a-5p, CDCA4, cell-free nucleic acids, molecular targets, breast cancer patient stratification

Yubo Yan, Xiangyuan Jin, HaoBo Sun, Sainan Pang, Xianglong Kong, Jianlong Bu, Shidong Xu Department of Thoracic Surgery, Harbin Medical University Tumer Hospital, Harbin, Heilongjiang Province, 150000, People’s Republic of ChinaCorrespondence: Shidong XuDepartment of Thoracic Surgery, Harbin Medical University Tumer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang Province, 150000, People’s Republic of ChinaTel +86-13903611962Email shidongxushi@sina.comObjective: To explore relevant mechanisms of miR-139-5p in alleviating the metastasis of non-small cell lung cancer cells (NSCLC) and their resistance against cisplatin.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) assays were carried out to determine the protein levels of miR-139-5p and YAF2, and cisplatin (DDP)-resistant NSCLC cell strains were established. Subsequently, an MTT assay was employed to evaluate the viability of the cell strains, a Transwell assay to evaluate cell invasion activity, and flow cytometry to analyze cell apoptosis rate. Finally, a Western blot assay was carried out to determine the protein levels of P-PI3K and p-p38.Results: NSCLC tissues showed lower miR-139-5p expression and higher YAF2 expression than paracancerous tissues and human normal lung epithelial cells, and miR-139-5p was related to the prognosis of NSCLC patients. Overexpression of miR-139-5p or knock-down of YAF2 inhibited the proliferation and invasion of NSCLC cells and induced their apoptosis. Additionally, the dual-luciferase reporter assay verified a targeting relationship between miR-139-5p and YAF2. Overexpression of miR-139-5p and knockdown of YAF2 reversed the resistance of A549/DDP cells against DDP, inactivated p38 and Akt proteins, and inhibited the AKT/p38 MAPK signaling pathway. Furthermore, inhibiting the AKT/p38 MAPK signaling pathway with MK2206 resisted the effects of knock-down of miR-139-5p on DDP resistance in NSCLC cells.Conclusion: MiR-139-5p targetedly regulates YAF2 and mediates the AKT/p38 MAPK signaling pathway to alleviate the metastasis of NSCLC cells and their resistance against cisplatin, which may be a novel target for improving the therapeutic effect on NSCLC.Keywords: miR-139-5p, YAF2, AKT/p38 MAPK, non-small cell lung cancer, cisplatin

Ting Cheng,1,2,* Yong Li,1,2,* Shuai Pang,1,2 HuanYing Wan,1,2 GuoChao Shi,2,3 QiJian Cheng,1,2 QingYun Li,2,3 ZiLai Pan,4 ShaoGuang Huang2,31Department of Respiratory Medicine, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Institute of Respiratory Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Radiology, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workBackgroud and objectives: Although lung attenuation distribution and lung volume on computed tomography (CT) have been widely used in evaluating COPD and interstitial lung disease, there are only a few studies regarding the normal range of these indices, especially in Chinese subjects. We aimed to describe the normal range of lung attenuation distribution and lung volume based on CT.Methods: Subjects with normal lung function and basically normal chest CT findings (derivation group) at Ruijin Hospital, Shanghai (from January 2010 to June 2014) were included according to inclusion and exclusion criteria. The range of the percentage of lung volume occupied by low attenuation areas (LAA%), percentile of the histogram of attenuation values (Perc n), and total lung volume were analyzed. Relationships of these measures with demographic variables were evaluated. Participants who underwent chest CT examination for disease screening and had basically normal CT findings served as an external validation group.Results: The number of subjects in the derivation group and external validation groups were 564 and 1,787, respectively. Mean total lung volumes were 4,468±1,271 mL and 4,668±1,192 mL, and median LAA%(-950 HU) was 0.19 (0.03–0.43) and 0.17 (0.01–0.41), in the derivation and external validation groups, respectively. Reference equations for lung volume and attenuation distribution (LAA% using -1,000–210 HU, Perc 1 to Perc 98) were generated: Lung volume (mL) = -1.015 *10^4+605.3*Sex (1= male, 0= female)+92.61*Height (cm) –12.99*Weight (kg) ±1766; LAA% (-950 HU)=[0.2027+0.05926*Sex (1= male, 0= female) –4.111*10^-3*Weight (kg) +4.924*10^-3*Height (cm) +8.504*10^-4*Age]^7.341–0.05; Upper limit of normal range: [0.2027+0.05926*Sex-4.111*10^-3*Weight+4.924*10^-3*Height+8.504*10^-4*Age+0.1993]^7.341–0.05.Conclusion: This large population-based retrospective study demonstrated the normal range of LAA%, Perc n, and total lung volume measured on CT scans among subjects with normal lung function and CT findings. Reference equations are provided.Keywords: lung attenuation, emphysema, lung volumes, quantitative computed tomography, reference equations, normal range, densitometry

Kankan Gao,1 Xiaoshan Guan,1 Lanlan Zeng,1 Jiabi Qian,2 Sufei Zhu,1 Qiulian Deng,1 Huamin Zhong,1 Shuying Pang,1 Fei Gao,1 Jielin Wang,1 Yan Long,1 Chien-Yi Chang,3 Haiying Liu1 1Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China; 2Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China; 3School of Chemistry and Biosciences, University of Bradford, Bradford, BD7 1DP, UK Background: A multidrug-resistant (MDR) RR2 gene cluster was identified by whole-genome sequencing in several highly virulent (ST-17) Group B streptococcus (GBS) isolates, which caused neonatal invasive infections in southern China in 2016. Tracing the transmission and distribution of MDR isolates in this area is important for the effective management of future infections. The aim of this study was to obtain longitudinal data of MDR isolates to monitor epidemiological trends of general common isolates in southern China, and provide evidence for future characterization of antimicrobial resistance mechanisms.Methods: Clinical information and antimicrobial susceptibility of GBS isolates were acquired from electronic information management system databases of the hospital under study between January 2011 and December 2017. To confirm the presence of intact RR2, the tetO, ant6, lnuB, and ant9 genes located upstream, midstream, and downstream of RR2 were detected by PCR and DNA sequencing.Results: A total of 149 cases of neonatal invasive GBS infection were identified during the period 2011–2017. Among them, 119 cases (79.9%) were caused by MDR isolates, with a general increasing trend over the past 7 years. Further characterization of 11 isolates showed that six isolates causing late-onset disease (LOD) carry the tetO, ant6, and lnuB genes, which are located on RR2. Moreover, lnuB and ant9 consistently co-occurred in GBS isolates, which suggests their close proximity to one another in the RR2 gene cluster.Conclusion: The MDR GBS is responsible for a large number of neonatal invasive infections and occurs with increasing frequency over time. Particularly, the MDR GBS isolates that cause LOD are more likely to carry the RR2 gene cluster, compared with those that cause early-onset disease. The rise in number of MDR GBS isolates emphasizes the pressing need for continuous surveillance to monitor their antibiotic susceptibility and epidemiology. Keywords: invasive infection, gene cluster, neonates, multidrug-resistance

Ting Cheng,1–3 Yong Li,1,3 Shuai Pang,1 Huan Ying Wan,1,3 Guo Chao Shi,3,4 Qi Jian Cheng,1,3 Qing Yun Li,3,4 Zi Lai Pan,5 Shao Guang Huang3,4 1Department of Respiratory Medicine, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2School of Public Health, Fudan University, Shanghai, China; 3Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 4Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 5Department of Radiology, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China Objective: The diagnostic value of emphysema extent in consistent air flow limitation remains controversial. Therefore, we aimed to assess the value of emphysema extent on computed tomography (CT) on the diagnosis of persistent airflow limitation. Furthermore, we developed a diagnostic criterion for further verification.Materials and methods: We retrospectively enrolled patients who underwent chest CT and lung function test. To be specific, 671 patients were enrolled in the derivation group (Group 1.1), while 479 patients were in the internal validation group (Group 1.2). The percentage of lung volume occupied by low attenuation areas (LAA%) and the percentile of the histogram of attenuation values were calculated.Results: In patients with persistent airflow limitation, the LAA% was higher and the percentile of the histogram of attenuation values was lower, compared with patients without persistent airflow limitation. Using LAA% with a threshold of -950 HU >1.4% as the criterion, the sensitivity was 44.3% and 47.2%, and the specificity was 95.2% and 95.7%, in Group 1.1 and Group 1.2, respectively. The specificity was influenced by the coexistence of interstitial lung disease, pneumothorax, and post-surgery, rather than the coexistence of pneumonia, nodule, or mass. Multivariable models were also developed.Conclusion: The emphysema extent on CT is a highly specific marker in the diagnosis of persistent airflow limitation. Keywords: computed tomography, lung function test, emphysema, persistent airflow limitation

Gao K, Guan X, Zeng L, et al. Infect Drug Resist. 2018;11:2561–2569.In this article both Wenjing Ji and David J McIver were erroneously listed in the acknowledgements but should have been included as coauthors. A communication error at the manuscript submission stage led to both authors being left off the original authorship list. Both Wenjing Ji and David J McIver were originally acknowledged for their assistance with formatting and proofreading and language editing, respectively. However, it was shown both authors also assisted with the interpretation of data and analysis, as well as assisting in drafting the manuscript, extensive editing, recommendations for analysis and the interpretation of findings. The authors wish to apologize for this error. The correct author list and affiliations are shown below.Read the original article

Fulfilling of household food security of lowland rice farmers require sufficient capacities to improve their productivity and income. Nowadays, lowland rice farmers are in difficult conditions and at risk to food security. This research aimed to analyze capacity, food security level, and copying mechanism of lowland rice farmer’s household based on land property right and to analyze the correlation between capacity and food security of lowland rice farmer’s household. This research utilized survey method on 200 lowland rice farmers household at Ogan Ilir and Ogan Komering Ilir District, South Sumatera. The data were analyzed by descriptive and Chi-square test. The results showed that the farmer’s capacities level was at middle category, the farmers’ household food security level was low, and coping mechanism of the farmers household was at high category. There was no significant correlation between capacity and food security of the lowland rice farmers household (p>0,05) also was found in this research.

Large detectors employing xenon are a leading technology in existing and planned searches for new physics, including searches for neutrinoless double beta decay (0νββ) and dark matter. While upcoming detectors will employ target masses of a ton or more, further extending gas- or liquid-phase Xe detectors to the kton scale would enable extremely sensitive next-generation searches for rare phenomena. The key challenge to extending this technology to detectors well beyond the ton scale is the acquisition of the Xe itself. We describe the motivation for extending Xe time-projection chambers to the kton scale and possible avenues for Xe acquisition that avoid existing supply chains. If acquisition of Xe in the required quantities is successful, kton-scale detectors of this type could enable a new generation of experiments, including searches for 0νββ at half-life sensitivities as long as 1030 yr.

OBJECTIVE: While current research suggests potential value for docosahexaenoic acid (DHA) in the prevention and management of atopic dermatitis (AD), the causal relationship between DHA and AD remains unclear, and the underlying mechanisms are not well understood. MATERIALS AND METHODS: To investigate the potential causal relationship between DHA and AD, as well as to explore potential mediating mechanisms, we employed the Mendelian randomization (MR) methods. To study these potential relationships, we conducted MR analysis using publicly available Genome-Wide Association Studies (GWAS) data. Effect estimates were computed using the random-effects inverse-variance weighted method. RESULTS: Our study demonstrates a negative correlation between DHA levels and AD risk (OR: 0.915, 95% CI: 0.858-0.975, p=0.007). Furthermore, in MR analysis using tumor necrosis factor ligand superfamily member 14 (TNFSF14) levels as an outcome, DHA levels also show a negative association with TNFSF14 levels (OR: 0.933, 95% CI: 0.879-0.990, p=0.022). Subsequently, we performed further analysis to explore the relationship between TNFSF14 and AD risk, revealing a positive correlation (OR: 1.069, 95% CI: 1.005-1.137, p=0.033). This suggests a potential mediating role of TNFSF14 in the impact of DHA on AD risk. CONCLUSIONS: In summary, our study employs MR analysis to offer genetic evidence indicating a potential role of DHA in reducing the risk of AD, as well as opening avenues for further in-depth investigation into potential mechanisms. These findings emphasize the importance of ongoing research in this field. [ABSTRACT FROM AUTHOR]

High-entropy alloys（HEAs）have attracted considerable attention from the research community as a pioneering alloy design paradigm over the past two decades. They have fundamentally challenged traditional design paradigms and exhibited exceptional mechanical properties and functional characteristics，thereby positioning themselves as promising candidates for significant engineering applications in the future. Recent advancements have unveiled several alloy systems that demonstrate exceptional performance across diverse metrics，including low-temperature fracture toughness，high-temperature strength，impact resistance，radiation tolerance，and fatigue resistance. These qualities render HEAs highly attractive materials for research with substantial application potential in critical domains such as deep space exploration，deep-sea investigations，low-temperature superconductivity，and advanced nuclear energy technologies. This paper will briefly introduce the concept and classification of HEAs，and review the experimental progress of HEAs under various extreme conditions such as extremely low temperatures，high-speed impacts，and high nuclear radiation. We also summarize the strategies for enhancing the strength and toughness of HEAs，and extract the deformation mechanisms and physical and chemical properties of HEAs under different extreme loads. It is foreseeable that the main development direction of HEAs will be to form microscopic fluctuations in chemical composition and construct multi-scalestructural ordering efficiently through fine adjustment of the selection and proportion of alloying elements and optimization of heat treatment processes. For comprehensive studies on HEAs subjected to extreme loads，it is essential to explore their microscopic deformation mechanisms further while proposing innovative strategies designed to address inherent trade-offs between strength and toughness. The integration of state-of-the-art simulation techniques combined with advanced characterization methods will be crucial for improving research efficiency while providing insights into microstructural behavior. Additionally，tailored optimization approaches should be implemented for distinct advantageous systems and phase structures，particularly those capable of activating dislocation movements，twinning，phase transformations and incorporating novel processing methodologies such as additive manufacturing. Finally，conducting more realistic simulation experiments that closely replicate extreme environments along with generating relevant engineering data are vital steps toward accelerating the practical application of HEAs in challenging settings.

Hong-Jing Zhu,1,&ast; Sheng-Yu Zhou,1,&ast; Yang Qu,1 Ying-Ying Sun,1 Ke-Jia Zhang,1 Shu-Yan Pang,1 Yi Yang,1 Zhen-Ni Guo1,2 1Stroke Center, Department of Neurology, The First Hospital of Jilin University, Chang Chun, People’s Republic of China; 2Neuroscience Research Center, Department of Neurology, The First Hospital of Jilin University, Chang Chun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen-Ni Guo; Yi Yang, Stroke Center, Department of Neurology, The First Hospital of Jilin University, Xinmin Street 1&num;, Changchun, 130021, People’s Republic of China, Tel +86-18186872986 ; +86-13756661217, Fax +86-431-88782378, Email zhen1ni2@163.com; yang_yi@jlu.edu.cnPurpose: Although recombinant tissue plasminogen activator (rt-PA) treatment is efficient in patients with acute ischemic stroke (AIS), a significant percentage of patients who received rt-PA intravenous thrombolysis (IVT) do not achieve a good prognosis. Therefore, the factors that affect the poor prognosis of patients with IVT are needed. The Fibrosis-4 (FIB-4) index has been used as a liver fibrosis biomarker. We aimed to investigate the relationship between the FIB-4 index and functional outcomes in patients with AIS receiving IVT.Patients and Methods: This study prospectively included consecutive patients with AIS receiving IVT between April 2015 and May 2022. We collected clinical and laboratory data and calculated the FIB-4 index. Clinical outcome was poor functional outcome (mRS ≥ 3) at 3 months after IVT. Multivariate logistic regression analysis was used to analyze the association between FIB-4 and outcome. We explored the interactive effect of FIB-4 and dyslipidemia on poor outcomes, and subgroup analysis was performed. Furthermore, an individualized prediction model based on the FIB-4 for functional outcome was established in the dyslipidemia group.Results: A total of 1135 patients were included, and 41.50% had poor 3-month outcomes. After adjusted by other variants that P value < 0.05 in univariable analysis, FIB-4 was independently associated with poor outcomes (OR=1.420; 95% CI: 1.113– 1.812; P=0.004). There was a significant interaction between FIB-4 and dyslipidemia on poor outcome (P=0.036), and the independent association between FIB-4 and poor outcome was maintained in the dyslipidemia subgroup (OR=1.646; 95% CI: 1.228– 2.206; P=0.001). Furthermore, in the dyslipidemia group, the FIB-4-based prediction model had good predictive value (the AUC of the training and validation sets were 0.767 and 0.708, respectively), good calibration (P-values for the Hosmer–Lemeshow test > 0.05), and clinical usefulness.Conclusion: FIB-4 is an independent risk factor for poor outcomes in IVT patients with dyslipidemia, which can be used as a simple predictor of their prognosis.Keywords: Fibrosis-4, acute ischemic stroke, intravenous thrombolysis, prognosis, dyslipidemia

AIM:To test and compare the perceptual eye position and fixation stability of adolescents with emmetropia and adolescents with low myopia, investigating the characteristics of the perceptual eye position and fixation stability of adolescents with low myopia.METHODS: Cross-sectional study. A total of 132 adolescents(264 eyes)who visited in the ophthalmology clinic of our hospital from April to December 2023 were randomly selected as the research subjects. Participants were categorized into normal control group(n=45, 90 eyes), simple low myopia group(n=45, 90 eyes)and low myopia with anisometropia group(n=42, 84 eyes)according to their refractive status and were underwent assessments for perceptual eye position and fixation stability.RESULTS: Compared with the normal control group, the static and dynamic horizontal perceptual eye position deviation of the simple low myopia group and the low myopia with anisometropia group were significantly increased(P0.05); compared with the normal control group, the horizontal and vertical fixation stability of the simple low myopia group and the low myopia with anisometropia group were significantly worse(all P0.05).CONCLUSION: Abnormalities are observed in perceptual eye position and fixation stability function in adolescents with low myopia compared with those adolescents with emmetropia, even at best corrected visual acuity. The occurrence of anisometropia could lead to an increased degree of horizontal perceptual eye position displacement.