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Dong Liu,1,&ast; Jianmin Wu,2,&ast; Han Wang,3 Hui Dong,3 Lei Chen,4 Ningyang Jia1 1Department of Radiology, The Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China; 2Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, 200438, People’s Republic of China; 3Department of Pathology, The Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China; 4The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ningyang Jia; Lei Chen, Email ningyangjia@163.com; chenlei@smmu.edu.cnObjective: To investigate the role of eosinophil counts (EC) in microvascular invasion (MVI) for enhancing the radiomics based diagnostic model. Additionally, its correlation with early recurrence and tumor immune microenvironment was explored.Methods: Propensity score matching was employed to evaluate on 462 cases whether EC was an independent risk factor for MVI. Subgroup analyses examined EC’s effect on MVI across varying hypersplenism degrees. Univariate-multivariate logistic regression identified MVI’s independent factors to develop a diagnostic model. Univariate-multivariate COX regression determined early recurrence factors. Co-detection by indexing (CODEX) constructed the immune score (IS), and Spearman correlation analyzed its association with peripheral immunity.Results: EC was an independent risk factor for MVI (p=0.038, OR=1.304 (95% CI: 1.014– 1.677)), and its effect on MVI disappeared with the severity of hypersplenism. The diagnostic model with EC was significantly improved (AUC=0.787 (95% CI: 0.737– 0.836) vs AUC=0.748(95% CI: 0.694– 0.802, p=0.005)). MVI was an independent risk factor for early recurrence (p< 0.001, HR = 2.254 (95% CI: 1.557– 3.263)). IS was negatively correlated with lymphocyte counts (R=− 0.311, p=0.022), and positively correlated with EC (R=0.301, p=0.027) and RS (R = 0.315, p = 0.018).Conclusion: EC was an independent risk factor for MVI and was related to the tumor immune microenvironment. EC should be included in the diagnosis of MVI to improve diagnostic efficiency.Keywords: hepatocellular carcinoma, eosinophils, radiomics

Chang-Sheng Ma,1,2,&ast; Ya-Ping Ma,1,3,&ast; Bo Han,1,2,&ast; Wan-Li Duan,1 Shu-Chen Meng,1 Min Bai,1 Hao Dong,1 Li-Ying Zhang,1 Meng-Yuan Duan,1,2 Jing Liu,1 Ai-Jun Deng,2 Mao-Tao He1,2 1Department of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Ophthalmology, Affiliated Hospital of Shandong Second Medical University, Weifang, People’s Republic of China; 3Department of Pathology, The 942Hospital of the People’s Liberation Army Joint Logistic Support Force, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mao-Tao He, Department of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China, Tel +86-18209617186, Fax +86-0536-3081201, Email hemaotao@sdsmu.edu.cn Ai-Jun Deng, Department of Ophthalmology, Affiliated Hospital of Shandong Second Medical University, Weifang, People’s Republic of China, Email dengaijun@hotmail.comPurpose: Ischemic stroke is a refractory disease wherein the reperfusion injury caused by sudden restoration of blood supply is the main cause of increased mortality and disability. However, current therapeutic strategies for the inflammatory response induced by cerebral ischemia-reperfusion (I/R) injury are unsatisfactory. This study aimed to develop a functional nanoparticle (MM/ANPs) comprising apelin-13 (APNs) encapsulated in macrophage membranes (MM) modified with distearoyl phosphatidylethanolamine-polyethylene glycol-RVG29 (DSPE-PEG-RVG29) to achieve targeted therapy against ischemic stroke.Methods: MM were extracted from RAW264.7. PLGA was dissolved in dichloromethane, while Apelin-13 was dissolved in water, and CY5.5 was dissolved in dichloromethane. The precipitate was washed twice with ultrapure water and then resuspended in 10 mL to obtain an aqueous solution of PLGA nanoparticles. Subsequently, the cell membrane was evenly dispersed homogeneously and mixed with PLGA-COOH at a mass ratio of 1:1 for the hybrid ultrasound. DSPE-PEG-RVG29 was added and incubated for 1 h to obtain MM/ANPs.Results: In this study, we developed a functional nanoparticle delivery system (MM/ANPs) that utilizes macrophage membranes coated with DSPE-PEG-RVG29 peptide to efficiently deliver Apelin-13 to inflammatory areas using ischemic stroke therapy. MM/ANPs effectively cross the blood-brain barrier and selectively accumulate in ischemic and inflamed areas. In a mouse I/R injury model, these nanoparticles significantly improved neurological scores and reduced infarct volume. Apelin-13 is gradually released from the MM/ANPs, inhibiting NLRP3 inflammasome assembly by enhancing sirtuin 3 (SIRT3) activity, which suppresses the inflammatory response and pyroptosis. The positive regulation of SIRT3 further inhibits the NLRP3-mediated inflammation, showing the clinical potential of these nanoparticles for ischemic stroke treatment. The biocompatibility and safety of MM/ANPs were confirmed through in vitro cytotoxicity tests, blood-brain barrier permeability tests, biosafety evaluations, and blood compatibility studies.Conclusion: MM/ANPs offer a highly promising approach to achieve ischemic stroke-targeted therapy inhibiting NLRP3 inflammasome-mediated pyroptosis. Keywords: apelin-13, cerebral ischemia-reperfusion injury, macrophage membrane, ischemic stroke therapy, pyroptosis

Menghan Yu,1 Xiaoshu Fu,1 Yanli Zhu,2 Miao Li,3 Min Wu,1 Entong Zhou,1 Hanwen Dong,1 Likun Wang,1 Ruoxi Wang,4 Fang Liu,2 Chunlai Jiang,1 Xiangwei Kong,5 Weiheng Su1,6 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2People’s Hospital of Jiangyuan District, Baishan, Jilin Province, People’s Republic of China; 3Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China; 4School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 5Changchun University of Science and Technology, Changchun, People’s Republic of China; 6Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Weiheng Su, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China, Email suweiheng@jlu.edu.cn Xiangwei Kong, Changchun University of Science and Technology, Changchun, People’s Republic of China, Email tenbpro@163.comPurpose: Tick-borne encephalitis virus (TBEV) infections result in severe central nervous system diseases in humans across Asia and Europe. In China, cases of tick-borne encephalitis are primarily caused by the Far East subtype of TBEV, which exhibits a distinct disease course compared to other extensively studied subtypes. However, there is limited knowledge regarding the nucleic acid and serological diagnostic characteristics of patients infected with the TBEV in China, which is the focus of investigation in the present study.Methods: This study established a TaqMan qPCR approach to detect TBEV RNA in the serum with optimal specificity, sensitivity, and precision. Using TaqMan qPCR and ELISA assay for TBEV IgM detection, serum samples from 63 hospitalized patients bitten by ticks in Northeast China were investigated for diagnostic characteristics.Results: Twenty-five patients were positive for viral RNA; nineteen patients were positive for IgM, and nine were positive for both viral RNA and IgM. Through comparative analysis, TBEV RNA copies were negatively correlated with the virus incubation period. IgM levels were positively correlated with the clinical symptom scores of patients. The severity of clinical symptoms and the length after the tick bite could be used to predict the IgM occurrence. Furthermore, IgM levels and viral RNA copies were not correlated in double-positive patients.Conclusion: Both nucleic acid and serological detection methods exhibited distinct windows for detecting TBEV infection, with some overlap, and were associated with specific correlated factors. This study provided novel insights into the diagnosis and course of TBEV-induced tick-borne encephalitis in China.Keywords: tick-borne encephalitis, TBE, tick-borne encephalitis virus, TBEV, TaqMan qPCR, IgM

Guoqin Wang,1,&ast; Xiaoying Hu,1,&ast; Nan Ye,1 Xiaoyi Xu,1 Weiyi Guo,1 Lijun Sun,1 Hongrui Dong,1 Xiaoyi Zhao,2 Hong Cheng1 1Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Division of Nephrology, Affiliated Hospital of Chifeng University, Neimenggu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Cheng, Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Beijing, 100029, People’s Republic of China, Email drchengh@163.comPurpose: In recent years, the incidence of malignancy patients with membranous nephropathy (MN) has gradually increased, but the clinical and pathological characteristics of these patients are still unclear. Our study aims at elucidating the clinical and pathological characteristics of malignancy patients with MN, especially the expression patterns of MN-specific antigens in both kidney and tumor tissue.Patients and Methods: A retrospective analysis was performed to summarize the clinical and pathological data of MN patients with malignancy at Beijing Anzhen Hospital from January 1, 2012, to December 31, 2022, followed by a thorough review of relevant literature published between May 1, 2000 to May 1, 2023 and case aggregation.Results: 19 patients in our center’s MN cohort and 21 patients from literature review were diagnosed with malignancy either before or after being diagnosed with MN. Among them, 16 (40.0%) and 17 (42.5%) patients tested PLA2R-only and THSD7A-only positive in renal tissue, respectively. And 16 of 26 patients showed similar staining in tumor and kidney tissues. Compared to the idiopathic membranous nephropathy (IMN) patients at our center, patients with malignancy were older, had a lower estimated glomerular filtration rate, and had a lower rate of partial or complete response to treatment. Renal tissue from MN patients with concomitant malignancy was less frequently PLA2R-positive, more frequently THSD7A-positive, and more often glomerular IgG subclass IgG2 (P = 0.033) but less frequently IgG4 (P < 0.001).Conclusion: The clinical and pathological characteristics of MN patients with concomitant malignancy are different from those of IMN patients. Active screening for malignancy should be performed in non-PLA2R-positive elderly MN patients with a poor therapeutic response. Staining for MN target antigens in kidney and tumor tissues may be inconsistent, and the role of MN target antigens needs to be further explored.Keywords: malignancy, membranous nephropathy, PLA2R, THSD7A, NELL-1

Lang Liu,1,&ast; Binghua Zhang,1,&ast; Zhenwei Zhou,2 Jie Yang,1 Ailin Li,1 Yongji Wu,1 Zeyu Peng,1 Xiangyan Li,2 Zhonghua Liu,3 Xiangyang Leng,1 Changwei Zhao,4 Haisi Dong,2 Wenhai Zhao4 1College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Northeast Asia Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 3Department of Orthopaedics, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 4Affiliated Hospital of Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haisi Dong, Northeast Asia Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, People’s Republic of China, Tel/Fax +86 431-18604361976, Email adonghaisi@163.com Wenhai Zhao, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130021, People’s Republic of China, Tel/Fax +86 431-86177836, Email zwh9899@163.comBackground: Knee osteoarthritis (KOA) is a persistent degenerative condition characterized by the deterioration of cartilage. The Chinese herbal formula Radix Rehmanniae Praeparata- Angelica Sinensis-Radix Achyranthis Bidentatae (RAR) has often been used in effective prescriptions for KOA as the main functional drug, but its underlying mechanism remains unclear. Therefore, network pharmacology and verification experiments were employed to investigate the impact and mode of action of RAR in the treatment of KOA.Methods: The destabilization of the medial meniscus model (DMM) was utilized to assess the anti-KOA effect of RAR by using gait analysis, micro-computed tomography (Micro-CT), and histology. Primary chondrocytes were extracted from the rib cartilage of a newborn mouse. The protective effects of RAR on OA cells were evaluated using a CCK‐8 assay. The antioxidative effect of RAR was determined by measuring reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) production. Furthermore, network pharmacology and molecular docking were utilized to propose possible RAR targets for KOA, which were further verified through experiments.Results: In vivo, RAR significantly ameliorated DMM-induced KOA characteristics, such as subchondral bone sclerosis, cartilage deterioration, gait abnormalities, and the degree of knee swelling. In vitro, RAR stimulated chondrocyte proliferation and the expression of Col2a1, Comp, and Acan. Moreover, RAR treatment significantly reduced ROS accumulation in an OA cell model induced by IL-1β and increased the activity of antioxidant enzymes (SOD and GSH). Network pharmacology analysis combined with molecular docking showed that Mapk1 might be a key therapeutic target. Subsequent research showed that RAR could downregulate Mapk1 mRNA levels in IL-1β-induced chondrocytes and DMM-induced rats.Conclusion: RAR inhibited extracellular matrix (ECM) degradation and oxidative stress response via the MAPK signaling pathway in KOA, and Mapk1 may be a core target.Keywords: knee osteoarthritis, RAR, cartilage degeneration, network pharmacology, Mapk1

The advancement of next-generation magnetic devices depends on fast manipulating magnetic microstructures at the nanoscale. A universal method is presented for rapid and reliable generating, controlling, and driving nano-scale skyrmioniums, through high-throughput micromagnetic simulations. Ultrafast switches are realized between skyrmionium and skyrmion states and rapidly change their polarities in monolayer magnetic nanodisks by perpendicular magnetic fields. The transition mechanism by alternating magnetic fields differs from that under steady magnetic fields. New skyrmionic textures, such as flower-like and windmill-like skyrmions, are discovered. Moreover, this nanoscale skyrmionium can move rapidly and stably in nanoribbons using weaker spin-polarized currents. Explicit discussions are held regarding the physical mechanisms involved in ultrafast manipulations of skyrmioniums. This work provides further physical insights into the manipulation and application of topological skyrmionic structures for developing low-power consumption and nanostorage devices. [ABSTRACT FROM AUTHOR]

Keyang Li,1,&ast; Debao Li,2,&ast; Hongliang Dong,1 Dongmei Ren,2 Dandan Gong,1 Shubo Wang,1 Yang Li,1 Yuanyuan Wu,1 Jikang Yang,3 Wenjuan Yan,4 Yi Li4 1Department of Clinical Pharmacy, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 2Department of Clinical Laboratory, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 3Infectious Diseases Department, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 4Department of Clinical Laboratory, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjuan Yan; Yi Li, Department of Clinical Laboratory, Henan Provincial People’s Hospital, Weiwu Road 7&num;, Jinshui District, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86 15225061830 ; +86 15939039006, Email yanwenjuan2008@126.com; liyilabmed@henu.edu.cnPurpose: Since the introduction of ceftazidime–avibactam (CZA) in the Chinese market, accumulating clinical evidence has substantiated its efficacy in the treatment of infections caused by carbapenem-resistant gram-negative bacteria (CR-GNB). Nevertheless, an ongoing debate persists concerning the choice between monotherapy and combination therapy when devising clinical anti-infection protocols.Patients and Methods: This retrospective, single-center observational study enrolled patients with CR-GNB infections who received CZA treatment between December 2019 and August 2023. The primary outcome assessed was 30-day mortality, and the secondary outcome measured was 14-day bacterial clearance. A multivariate Cox regression model was used to identify variables that were independently associated with 30-day mortality rate.Results: Eighty-three patients were enrolled in the study; of which, 45 received CZA monotherapy, whereas 38 received combination therapy. The overall 30-day mortality rate was 31.3%, and no significant difference was observed in the 30-day mortality rates between the CZA combination therapy and monotherapy groups (31.6% vs 31.1%, p=0.963). After adjustment by propensity score matching, the 30-day mortality rate was not significantly different between the two groups (28.6% vs 31.4%, p=0.794). Multivariate COX analysis revealed that age and SOFA score were independent predictors of 30-day mortality.Conclusion: Combination therapy with CZA and other antimicrobials was not found to have an advantage over monotherapy in reducing the 30-day mortality rate.Keywords: ceftazidime-avibactam, carbapenem-resistant gram-negative bacteria, combination therapy K. pneumoniae carbapenemase

Yue Wang,1 Jie Chen,1 Han Dong,2 Rui-Lin Ma,1 Ying Zou,3 Wei Wang,4 Qingmei Zheng,5 Ying Feng,6 Zhangyun Tan,7 Xiaoqin Zeng,8 Yinqing Zhao,7 Yan Deng,1 Yanfang Wang,1 Bei Gu,9 Aijun Sun1,10 1National Clinical Research Center for Obstetric & Gynecologic Diseases Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women and Children’s Hospital of Jinzhou, Jinzhou, Liaoning, 121000, People’s Republic of China; 3Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, 410008, People’s Republic of China; 4Department of Reproductive Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 5Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266500, People’s Republic of China; 6Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 7Department of Obstetrics and Gynecology, Xinhui Maternity and Children’s Hospital, Nanning, Guangxi, 529100, People’s Republic of China; 8Department of Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong, 510000, People’s Republic of China; 9Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, 100038, People’s Republic of China; 10Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, 100010, People’s Republic of ChinaCorrespondence: Aijun Sun, Email saj@pumch.cnBackground: The basic medical education stage is not enough to support physicians to fully diagnose and evaluate polycystic ovary syndrome (PCOS). The study aims to discover the difference in treatment choice between participants with different annual consultation number of PCOS, to promote lifelong learning, and drive balanced development within healthcare.Methods: This is a multicenter cross-sectional survey. Participants’ basic information, knowledge of PCOS and treatment options were collected online. According to the annual consultation number of patients with PCOS, physicians were divided into three groups: 0– 50 people/yr, 50– 200 people/yr, and > 200 people/yr, and the results were derived from χ2 test, Fisher exact test, and multivariate logistic regression analysis.Results: The study analyzed 1689 questionnaires, and 1206 physicians (71.4%) received less than 50 women per year, 388 physicians (30.0%) with an annual number of 50– 200 women, and 95 physicians (5.6%) with patient turnover for more than 200 people. Reproductive endocrinologists generally have higher access to the clinic. As the number of visits increases, more and more physicians would perceive patients as more likely to have abnormal blood glucose and heavy weight. Physicians with large numbers of consultations are more likely to use Asian or Chinese standards to assess obesity. The multivariate analysis involved variables such as age, hospital level, specialty, and patient turnover annually, and more young doctors actively assessed lipid profile (odds ratio (OR) 1.56, 95% confidence interval (CI) (1.16, 2.16)), and primary hospitals (OR 0.65 CI (0.44, 0.89)) chose OGTT for blood glucose assessment less than tertiary hospitals. Physicians in secondary hospitals are more aggressive in evaluating androgens.Conclusion: Our survey found differences in endocrine assessment, metabolic screening, and treatment in PCOS women in terms of the number of obstetrician-gynecologists who received different patient consultation numbers. The importance of continuing education for physicians is emphasized, to promote lifelong learning.Keywords: polycystic ovary syndrome, consultation number, lifelong learning, insulin resistance, obesity, hyperandrogenemia, metformin

Rui Jing,1 Hui Dong,1 Kun Huang,2 Zhong Liu,1 Ran Xue,1 Yiran Dong,1 Mei Jiao,3 Na Li,4 Yumei Guo,5 Yun Liu,6 Wenqian Zhang,1 Hongyun Sun1 1Institute for Tuberculosis Control, Jinan Center for Disease Control and Prevention, Jinan, People’s Republic of China; 2Tuberculosis Control Division, Licheng Center for Disease Control and Prevention, Jinan, People’s Republic of China; 3Department of Sexually Transmitted Diseases and AIDS Prevention and Control, Lixia Center for Disease Control and Prevention, Jinan, People’s Republic of China; 4Tuberculosis and Vector Control Division, Shizhong Center for Disease Control and Prevention, Jinan, People’s Republic of China; 5Department of Infectious Diseases and Endemic Disease Control, Huaiyin Center for Disease Control and Prevention, Jinan, People’s Republic of China; 6AIDS Prevention and Control Department, Tianqiao Center for Disease Control and Prevention, Jinan, People’s Republic of ChinaCorrespondence: Wenqian Zhang; Hongyun Sun, Institute for Tuberculosis Control, Jinan Center for Disease Control and Prevention, Jinan, People’s Republic of China, Tel +86 0531-81278897 ; +86 0531 81278873, Email wqzh618@gmail.com; jncdcxxtb@jn.shandong.cnPurpose: This study aimed to investigate awareness of tuberculosis control among post-treatment tuberculosis patients, in order to provide a basis for future preventive and control work in this population.Patients and Methods: A cross-sectional descriptive study was conducted on post-treatment patients with tuberculosis in seven districts of Jinan City between July 2021 and December 2022. A face-to-face or telephone interviews using structured questionnaires for the research subjects were conducted by data collectors. Analyses were carried out first for all subjects, and then separately for male and female subjects.Results: A total of 837 valid questionnaires were collected, of which 495 were males and 342 were females. The awareness rate of the core TB knowledge was 82.46%. The ≥ 65 year group in the total group (OR=0.43, 95% CI: (0.28, 0.68)), male (OR=0.47, 95% CI: (0.27, 0.83)) and female group (OR=0.40, 95% CI: (0.19, 0.86)) was lower than that of the control group. Educational level and monthly income are the main factors of TB cognition in total group. People with university or higher education (OR=2.05, 95% CI: (1.38, 3.05)) and with a monthly income of ≥ 6,000 (OR=1.89, 95% CI: (1.10, 3.25)) had a higher awareness rate. The group with current residence in the city was more aware than the reference group.Conclusion: In the future, the communication of the main transmission route, suspicious symptoms, and cure of TB needs to be strengthened for the post-treatment TB patients. The elderly, those with secondary school education or below, agricultural workers and low-income people are the groups with weak knowledge of TB, and they are also the groups that need to be focused on health education. The above information should be focused on the above groups of people in order to educate them in a way that is easily acceptable to them.Keywords: pulmonary tuberculosis, awareness rate, completed treatment patients, layered analysis

Abstract Quantum interference between reaction pathways around a conical intersection (CI) is an ultrasensitive probe of detailed chemical reaction dynamics. Yet, for the hydrogen exchange reaction, the difference between contributions of the two reaction pathways increases substantially as the energy decreases, making the experimental observation of interference features at low energy exceedingly challenging. We report in this paper a combined experimental and theoretical study on the H + HD → H2 + D reaction at the collision energy of 1.72 eV. Although the roaming insertion pathway constitutes only a small fraction (0.088%) of the overall contribution, angular oscillatory patterns arising from the interference of reaction pathways were clearly observed in the backward scattering direction, providing direct evidence of the geometric phase effect at an energy of 0.81 eV below the CI. Furthermore, theoretical analysis reveals that the backward interference patterns are mainly contributed by two distinct groups of partial waves (J ~ 10 and J ~ 19). The well-separated partial waves and the geometric phase collectively influence the quantum reaction dynamics.

Jieliang Liu,1,&ast; Junguo Jin,1,&ast; Bingyan Yu,2 Shanghong Zhang,2 Xiaoqi Lu,1 Guoqiang Chen,2 Yi Yang,2 Haojian Dong1,3 1Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People’s Republic of China; 2Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Nyingchi People’s Hospital, Nyingchi, Tibet, 860000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haojian Dong, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, People’s Republic of China, Email donghaojian@gdph.org.cn Yi Yang, Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China, Email 13825084233@163.comBackground: Discordance between the anatomy and physiology of the coronary has important implications for managing patients with stable coronary disease, but its significance in ST-elevation myocardial infarction has not been fully elucidated.Methods: The retrospective study involved patients diagnosed with ST-elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention (PCI), along with quantitative coronary angiography (QCA) and quantitative flow ratio (QFR) assessments. Patients were stratified into four groups regarding the severity of the culprit vessel, both visually and functionally: concordantly negative (QCA-diameter stenosis [DS] ≤ 50% and QFR > 0.80), mismatch (QCA-DS > 50% and QFR > 0.80), reverse mismatch (QCA-DS ≤ 50% and QFR ≤ 0.80), and concordantly positive (QCA-DS > 50% and QFR ≤ 0.80). Multivariable logistic regression analyses were conducted to identify the clinical factors linked to visual-functional mismatches. Kaplan‒Meier analysis was conducted to estimate the 18-month adverse cardiovascular events (MACE)-free survival between the four groups.Results: The study involved 310 patients, with 68 presenting visual-functional mismatch, and 51 exhibiting reverse mismatch. The mismatch was associated with higher angiography-derived microcirculatory resistance (AMR) (adjusted odds ratio [aOR]=1.016, 95% CI: 1.010– 1.022, P< 0.001). Reverse mismatch was associated with larger area stenosis (aOR=1.044, 95% CI: 1.004– 1.086, P=0.032), lower coronary flow velocity (aOR=0.690, 95% CI: 0.567– 0.970, P< 0.001) and lower AMR (aOR=0.947, 95% CI: 0.924– 0.970, P< 0.001). Additionally, the mismatch group showed the worst 18-month MACE-free survival among the four groups (Log rank test p = 0.013).Conclusion: AMR plays a significant role in the occurrence of visual-functional mismatches between QCA-DS and QFR, and the mismatch group showed the worst prognosis.Keywords: ST-elevation myocardial infarction, quantitative coronary angiography, quantitative flow ratio, angiography-derived microcirculatory resistance

Hao Dong,1,&ast; Rong Chen,2,&ast; Fang Xu,3,&ast; Fang Cheng4 1Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Rehabilitation Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 3Clinical Medical Laboratory Center, Taizhou People’s Hospital, Taizhou, Jiangsu, 225300, People’s Republic of China; 4Department of Gastroenterology, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Cheng, Department of Gastroenterology, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, No. 1 Yintan Road, Dongxihu District, Wuhan, 430023, Hubei Province, People’s Republic of China, Email 13886178189@163.comBackground and Aims: Cholelithiasis etiology intricately involves lipid metabolism. We sought to investigate the plausible causal link between genetically proxied lipid-lowering medications—specifically HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors—and cholelithiasis risk.Methods: Our study utilized two genetic instruments for exposure to lipid-lowering drugs. These instruments encompassed genetic variants linked to low-density lipoprotein (LDL) cholesterol within or in proximity to drug target genes, along with loci governing gene expression traits of these targets. Effect estimates were derived through Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) methods.Results: Higher HMGCR-mediated LDL cholesterol levels (IVW-MR, OR = 2.15, 95% CI = 1.58– 2.94; P = 0.000) and increased HMGCR expression (SMR, OR = 1.19, 95% CI = 1.04– 1.37; P = 0.014) are linked to elevated cholelithiasis risk, suggesting potential benefits of HMGCR inhibition. In contrast, higher PCSK9-mediated LDL cholesterol levels (IVW-MR, OR = 0.72, 95% CI = 0.56– 0.94; P = 0.015) and increased PCSK9 expression (SMR, OR = 0.90, 95% CI = 0.82– 0.99; P = 0.035) both correlate with lower cholelithiasis risk, indicating that PCSK9 inhibition may elevate this risk. Nevertheless, no substantial link emerged between NPC1L1-mediated LDL cholesterol or NPC1L1 expression and cholelithiasis in both IVW-MR and SMR analyses.Conclusion: This MR investigation affirms the causal link between the utilization of HMGCR inhibitors and a diminished risk of cholelithiasis. Additionally, it indicates a causal link between PCSK9 inhibitors use and increased cholelithiasis risk. However, no significant correlation was found between NPC1L1 inhibitors use and cholelithiasis risk.Keywords: cholelithiasis, lipid-lowering drugs, Mendelian randomization analysis, HMGCR inhibitors, PCSK9 inhibitors, NPC1L1 inhibitors

Han Wang,1,&ast; Jun-Jie Chen,2,&ast; Shu-Yi Yin,3,&ast; Xia Sheng,4 Hong-Xia Wang,5 Wan Yee Lau,6 Hui Dong,1 Wen-Ming Cong1 1Department of Pathology, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, People’s Republic of China; 3Department of Pathology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 4Department of Pathology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 5Department of Pathology, Jiading District Central Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, People’s Republic of China; 6Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China&ast;These authors contributed equally to this workCorrespondence: Hui Dong; Wen-Ming Cong, Department of Pathology, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel +86-021-81875191 ; +86-021-81875192, Email huidongwh@126.com; wmcong@smmu.edu.cnBackground: Microvascular invasion (MVI) is closely correlated with poor clinical outcomes in patients with hepatocellular carcinoma (HCC). A grading system of MVI is needed to assist in the management of HCC patient.Methods: Multicenter data of HCC patients who underwent liver resection with curative intent was analyzed. This grading system was established by detected number and distance from tumor boundary of MVI. Survival outcomes were compared among patients in each group. This system was verified by time-receiver operating characteristic curve, time-area under the curve, calibration curve, and decision curve analyses. Cox regression analysis was performed to study the associated factors of prognosis. Logistic analysis was used to study the predictive factors of MVI.Results: All patients were classified into 4 groups: M0: no MVI; M1: 1~5 proximal MVIs (≤ 1 cm from tumor boundary); M2a: > 5 proximal MVIs (≤ 1 cm from tumor boundary); M2b: ≥ 1 distal MVIs (> 1 cm from tumor boundary). The recurrence-free survival (RFS), overall survival (OS), and early RFS rates among all the individual groups were significantly different. Based on the number of proximal MVI (0~5 vs > 5), patients in the M2b group were further divided into two subgroups which also showed different prognosis. Multiple methods showed this grading system to be significantly better than the MVI two-tiered system in prognostic evaluation. Four multivariate models for RFS, OS, early RFS, late RFS, and a predictive model of MVI were then established and were shown to satisfactorily evaluate prognosis and have a great discriminatory power, respectively.Conclusion: This MVI grading system could precisely evaluate prognosis of HCC patients after liver resection with curative intent and it could be employed in routine pathological reports. The severity of MVI from both adjacent and distant from tumor boundary should be stated. A hypothesis about two occurrence modes of distal MVI was proposed. Keywords: hepatocellular carcinoma, microvascular invasion, hepatectomy, hepatic resection, pathology

This study presents a parallel algorithm for high-dimensional quantum dynamics simulations in poly atomic reactions, integrating distributed- and shared-memory models. The distributions of the wave function and potential energy matrix across message passing interface processes are based on bundled radial and angular dimensions, with implementations featuring either two- or one-sided communication schemes. Using realistic parameters for the H + NH3 reaction, performance assessment reveals linear scalability, exceeding 90% efficiency with up to 600 processors. In addition, owing to the universal and concise structure, the algorithm demonstrates remarkable extensibility to diverse reaction systems, as demonstrated by successes with six-atom and four-atom reactions. This work establishes a robust foundation for high-dimensional dynamics studies, showcasing the algorithm's efficiency, scalability, and adaptability. The algorithm's potential as a valuable tool for unraveling quantum dynamics complexities is underscored, paving the way for future advancements in the field. [ABSTRACT FROM AUTHOR]

We present a comprehensive investigation into the dissociative chemisorption of HOD on a rigid Ni(100) surface using an approximate full-dimensional (9D) quantum dynamics approach, which was based on the time-dependent wave-packet calculations on a full-dimensional potential energy surface obtained through neural network fitting to density functional theory energy points. The approximate-9D probabilities were computed by averaging the seven-dimensional (7D) site-specific dissociation probabilities across six impact sites with appropriate relative weights. Our results uncover a distinctive bond-selective effect, demonstrating that the vibrational excitation of a specific bond substantially enhances the cleavage of that excited bond. The product branching ratios are substantially influenced by which bond undergoes excitation, exhibiting a clear preference for the product formed through the cleavage of the excited bond over the alternative product. [ABSTRACT FROM AUTHOR]

Polanyi's rules predict that a late-barrier reaction yields vibrationally cold products; however, experimental studies showed that the H2 product from the late-barrier H + H2O(|04⟩−) and H + HOD(vOH = 4) reactions is vibrationally hot. Here, we report a potential-averaged five-dimensional state-to-state quantum dynamics study for the H + HOD(vOH = 0–4) → H2 + OD reactions on a highly accurate potential energy surface with the total angular momentum J = 0. It is found that with the HOD vibration excitation increasing from vOH = 1 to 4, the product H2 becomes increasingly vibrationally excited and manifests a typical characteristic of an early barrier reaction for vOH = 3 to 4. Analysis of the scattering wave functions revealed that vibrational excitation in the breaking OH bond moves the location of dynamical saddle point from product side to reactant side, transforming the reaction into an early barrier reaction. Interestingly, pronounced oscillatory structures in the total and product vibrational-state-resolved reaction probabilities were observed for the H + HOD(vOH = 3, 4) reactions, in particular at low collision energies, which originate from the Feshbach resonance states trapped in the bending/torsion excited vibrational adiabatic potential wells in the entrance region due to van der Waals interactions. [ABSTRACT FROM AUTHOR]

The 6D time-dependent wave packet calculations were performed to explore H2 dissociation on Ag, Au, and two AgAu alloy surfaces, using four newly fitted potential energy surfaces based on the neural network fitting to density functional theory energy points. The ligand effect resulting from the Ag–Au interaction causes a reduction in the barrier height for H2+Ag/Au(111) compared to H2+Ag(111). However, the scenario is reversed for H2+Au/Ag(111) and H2+Au(111). The 6D dissociation probabilities of H2 on Ag/Au(111) surfaces are significantly higher than those on the pure Ag(111) surface, but the corresponding results for H2 on Au/Ag(111) surfaces are substantially lower than those on the pure Au(111) surface. The reactivity of H2 on Au(111) is larger than that on Ag(111), despite Ag(111) having a slightly lower static barrier height. This can be attributed to the exceptionally small dissociation probabilities at the hcp and fcc regions, which are at least 100 times smaller compared to those at the bridge or top site for H2+Ag(111). Due to the late barrier being more pronounced, the vibrational excitation of H2 on Ag(111) is more effective in promoting the reaction than on Au(111). Moreover, a high degree of alignment dependence is detected for the four reactions, where the H2 dissociation has the highest probability at the helicopter alignment, as opposed to the cartwheel alignment. [ABSTRACT FROM AUTHOR]

Pineapple mealybug, Dysmicoccus brevipes (Hemiptera: Pseudococcidae), is a significant pest in pineapple production and a key trade barrier. We explored the potential use of ethyl formate (EF) as a methyl bromide alternative for the postharvest fumigation of D. brevipes in imported pineapples. When treated at 8 °C for 4 h, EF fumigation was effective against D. brevipes with LCt99, the lethal concentration × time product of EF necessary to achieve 99% mortality of D. brevipes nymphs and adults at 64.2 and 134.8 g h/m3, respectively. Sorption trials conducted with 70 g/m3 EF for 4 h at 8 °C using 7.5, 15 and 30% pineapple loading ratios (w/v) indicated that loading ratio lower than 30% is necessary to achieve the LCt99 values required to control D. brevipes. In a scaled up trial using 1 m3 chamber, EF fumigation with 70 g/m3 for 4 h at 8 °C with 20% pineapple loading ratio (w/v) resulted in a complete control of D. brevipes treated. There were no significant differences in hue values, sugar contents, firmness, and weight loss between EF-treated and untreated pineapples. Our results suggest that EF is a promising alternative to methyl bromide fumigation for the postharvest phytosanitary disinfection of D. brevipes in pineapples.

We investigate the current-phase relations of Al/InAs-quantum well planar Josephson junctions fabricated using nanowire shadowing technique. Based on several experiments, we conclude that the junctions exhibit an unusually large second-order Josephson harmonic, the $\sin(2\varphi)$ term. First, superconducting quantum interference devices (dc-SQUIDs) show half-periodic oscillations, tunable by gate voltages as well as magnetic flux. Second, Josephson junction devices exhibit kinks near half-flux quantum in supercurrent diffraction patterns. Third, half-integer Shapiro steps are present in the junctions. Similar phenomena are observed in Sn/InAs quantum well devices. We perform data fitting to a numerical model with a two-component current phase relation. Analysis including a loop inductance suggests that the sign of the second harmonic term is negative. The microscopic origins of the observed effect remain to be understood. We consider alternative explanations which can account for some but not all of the evidence.

In this study, we introduce a method designed to eliminate parallax artefacts present in X-ray powder diffraction computed tomography data acquired from large samples. These parallax artefacts manifest as artificial peak shifting, broadening and splitting, leading to inaccurate physicochemical information, such as lattice parameters and crystallite sizes. Our approach integrates a 3D artificial neural network architecture with a forward projector that accounts for the experimental geometry and sample thickness. It is a self-supervised tomographic volume reconstruction approach designed to be chemistry-agnostic, eliminating the need for prior knowledge of the sample's chemical composition. We showcase the efficacy of this method through its application on both simulated and experimental X-ray powder diffraction tomography data, acquired from a phantom sample and an NMC532 cylindrical lithium-ion battery. [ABSTRACT FROM AUTHOR]

Potential-averaged fivedimensional (PA5D) time-dependent wave packet calculations have been carried out to obtain the initial state-specific reaction probabilities and rate constants for a series of reactant rotationally excited states of the title reaction on one of our recently developed potential energy surface (F12a PES). It is found that individual excitation of the reactant HC1 to j1=2 or OH to j2=1 yields the largest total reaction probability except for low collision energies. In the low energy region, the resonance enhancement of reaction probability decreases rapidly with the increase of OH rotational excitation, resulting in a rapid decline in the rate constant below 250 K. The rate constant of the simultaneous HC1 and OH rotational excitation is not a simple superposition of the results of the separate excitation. Finally, we obtain the thermal rate constants of the reaction by Boltzmann averaging the rate constants for initial rotational states up to (5, 5), which are in reasonable agreement with the experimental results. [ABSTRACT FROM AUTHOR]

Quantum interference between reaction pathways around a conical intersection (CI) is an ultrasensitive probe of detailed chemical reaction dynamics. Yet, for the hydrogen exchange reaction, the difference between contributions of the two reaction pathways increases substantially as the energy decreases, making the experimental observation of interference features at low energy exceedingly challenging. We report in this paper a combined experimental and theoretical study on the H + HD → H2 + D reaction at the collision energy of 1.72 eV. Although the roaming insertion pathway constitutes only a small fraction (0.088%) of the overall contribution, angular oscillatory patterns arising from the interference of reaction pathways were clearly observed in the backward scattering direction, providing direct evidence of the geometric phase effect at an energy of 0.81 eV below the CI. Furthermore, theoretical analysis reveals that the backward interference patterns are mainly contributed by two distinct groups of partial waves (J ~ 10 and J ~ 19). The well-separated partial waves and the geometric phase collectively influence the quantum reaction dynamics. In a combined experimental and theoretical study of the H + HD → H2 + D reaction at low collision energy (1.72 eV), the authors obtain detailed information on the quantum reaction dynamics surrounding a conical intersection. [ABSTRACT FROM AUTHOR]

Bacterial symbionts are crucial to the biology of Bactrocera dorsalis. With larval diet (fruit host) being a key factor that determines microbiome composition and with B. dorsalis using more than 400 fruits as hosts, it is unclear if certain bacterial symbionts are preserved and are passed on to B. dorsalis progenies despite changes in larval diet. Here, we conducted a fly rearing experiment to characterize diet-induced changes in the microbiome of female B. dorsalis. In order to explicitly investigate the impacts of larval diet on the microbiome, including potential stable bacterial constituents of B. dorsalis, we performed 16S rRNA sequencing on the gut tissues of teneral female flies reared from four different host fruits (guava, mango, papaya, and rose apple) infested using a single cohort of wild B. dorsalis that emerged from tropical almond (mother flies). Although B. dorsalis-associated microbiota were predominantly shaped by the larval diet, some major bacterial species from the mother flies were retained in progenies raised on different larval diets. With some variation, Klebsiella (ASV 1 and 2), Morganella (ASV 3), and Providencia (ASV 6) were the major bacterial symbionts that were stable and made up 0.1–80% of the gut and ovipositor microbiome of female teneral flies reared on different host fruits. Our results suggest that certain groups of bacteria are stably associated with female B. dorsalis across larval diets. These findings provide a basis for unexplored research on symbiotic bacterial function in B. dorsalis and may aid in the development of novel management techniques against this devastating pest of horticultural importance. [ABSTRACT FROM AUTHOR]

The interface heat transfer of two layers induced by van der Waals (vdW) contacts is theoretically investigated, based on first-principles calculations at low temperatures. The results suggest that out-of-plane acoustic phonons with low frequencies dominate the interface thermal transport due to the vdW interaction. The interface thermal conductivity is proportional to the cubic of temperature at very low temperatures, but becomes linearly proportional to temperature as temperature increases. We show that manipulating the strain alters vdW coupling, leading to increased interfacial thermal conductivity at the interface. Our findings provide valuable insights into the interface heat transport in vdW heterostructures and support further design and optimization of electronic and optoelectronic nanodevices based on vdW contacts. [ABSTRACT FROM AUTHOR]