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Qian Wu,1,* Qing-Qing Dong,1,* Si-Hui Wang,1 Yi Lu,1 Yi Shi,1 Xiao-Ling Xu,2 Wei Chen1 1ICU, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shulan International Medical College, Zhejiang Shuren University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Chen, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 725 South WanPing Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-64385700-3522, Email cwdoctor@shutcm.edu.cn Xiao-Ling Xu, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren Street, Hangzhou, 310015, People’s Republic of China, Email ziyao1988@zju.edu.cnBackground: Sepsis continues to exert a significant impact on morbidity and mortality in clinical settings, with immunosuppression, multi-organ failure, and disruptions in gut microbiota being key features. Although rheinic acid and tanshinone IIA show promise in mitigating macrophage apoptosis in sepsis treatment, their precise targeting of macrophages remains limited. Additionally, the evaluation of intestinal flora changes following treatment, which plays a significant role in subsequent cytokine storms, has been overlooked. Leveraging the innate inflammation chemotaxis of tumor cell-derived exosomes allows for their rapid recognition and uptake by activated macrophages, facilitating phenotypic changes and harnessing anti-inflammatory effects.Methods: We extracted exosomes from H1299 cells using a precipitation method. Then we developed a tumor cell-derived exosomal hybrid nanosystem loaded with rhubarbic acid and tanshinone IIA (R+T/Lipo/EXO) for sepsis treatment. In vitro studies, we verify the anti-inflammatory effect and the mechanism of inhibiting cell apoptosis of nano drug delivery system. The anti-inflammatory effects, safety, and modulation of intestinal microbiota by the nanoformulations were further validated in the in vivo study.Results: Nanoformulation demonstrated enhanced macrophage internalization, reduced TNF-α expression, inhibited apoptosis, modulated intestinal flora, and alleviated immunosuppression.Conclusion: R+T/Lipo/EXO presents a promising approach using exosomal hybrid nanosystems for treating sepsis. Keywords: sepsis, rheinic acid, tanshinone IIA, exosome, hybrid nanosystem

Several investigations have demonstrated the association of MTSS1 with left ventricular (LV) structure and function. A recently published study has even revealed that rs35006907 was associated with both MTSS1 expression and the risk of dilated cardiomyopathy (DCM).

Rajiha A Ibrahim,1– 3 Nega Berhe,1 Zelalem Mekuria,3,4 Eyasu T Seyoum,3 Joan-Miquel Balada-Llasat,3,5 Tamrat Abebe,6 Solomon H Mariam,1 Estifanos Tsige,2 Surafel Fentaw Dinku,2 Shu-Hua Wang3,7 1Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia; 2Bacterial, Parasitic and Zoonotic Research Directorate, Ethiopian Public Health Institute, Addis Ababa, Ethiopia; 3Global One Health Initiative (GOHi), The Ohio State University, Columbus, OH, USA; 4Veterinary Preventive Medicine, Colleges of Veterinary Medicine, The Ohio State University, Columbus, OH, USA; 5Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, USA; 6Department of Microbiology, Immunology, and Parasitology, Schools of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 7Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USACorrespondence: Rajiha A Ibrahim, Bacterial, Parasitic and Zoonotic Research Directorate, Ethiopian Public Health Institute, PO Box: 1242, Addis Ababa, Ethiopia, Tel +251920602640, Email rajihabubeker@gmail.com; Ibrahim.258@osu.eduBackground: Staphylococcus aureus causes a wide range of infections from mild skin and soft tissue to severe life-threatening bacteremia. The pathogenicity of S. aureus infections is related to various bacterial surface components and extracellular proteins such as toxic-shock syndrome (TSS) toxin and Panton-Valentine leukocidin (PVL). In this study we determine the antimicrobial resistance of isolated strains and their virulence genes in Ethiopia.Methods: A total of 190 archived S. aureus isolates from four Ethiopia Antimicrobial Resistance (AMR) Surveillance sites were analyzed. The identification of S. aureus was done by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF Biotyper) and antimicrobial susceptibility test (AST) was done using VITEK® 2. Multiplex PCR was used to detect mecA, mecC, pvl and spa genes and super-antigens (sea, seb, sec, seh and sej staphylococcal enterotoxins).Results: A total of 172 isolates were confirmed as S. aureus, 9 (5.23%) were methicillin-resistant S. aureus (MRSA) and 163 (94.76%) were methicillin-susceptible S. aureus (MSSA). AST showed that 152 (88.4%) isolates were resistant to penicillin; 90 (52.32%) resistant to trimethoprim-sulfamethoxazole; and 45 (26.16%) resistant to tetracycline. A total of 66 (38.37%) isolates harbored at least one staphylococcal enterotoxin gene and 31 (46.96%) isolates had more than one. The most frequent enterotoxin gene encountered was seb 28 (16.28%). The TSST-1 gene was detected in 23 (13.37%). Presence of staphylococcal enterotoxin gene showed significant association with antibiotic resistance to cefoxitin, benzylpenicillin, oxacillin, erythromycin, clindamycin, tetracycline and SXT. The pvl gene was detected in 102 (59.3%) of isolates. Isolates from patients below 15 years of age showed significantly high numbers of pvl gene (P = 0.02). Presence of sej (P = 0.011) and TSST-1 (P < 0.001) genes were associated with the presence of pvl gene.Conclusion: In this study, isolates were highly resistant to oral antibiotics and the pvl, seb, sea and TSST-1 genes were prevalent.Keywords: MRSA, enterotoxin genes, Panton-Valentine leucocidin, PVL, Ethiopia

Yun Hong,1,&ast; Da-Peng Dai,2,&ast; Jian-Ping Cai,2 Shuang-Hu Wang,3 Yi-Ran Wang,1,4 Fang-Ling Zhao,2,4 Shan Zhou,2 Quan Zhou,3 Pei-Wu Geng,3 Yun-Fang Zhou,3 Xue Xu,1 Ji-Hua Shi,1 Qing-Feng Luo1 1Department of Gastroenterology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 2The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, 100730, People’s Republic of China; 3Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui, 323020, People’s Republic of China; 4Peking University Fifth School of Clinical Medicine, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing-Feng Luo, Department of Gastroenterology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Tel + 86 138 1151 9095, Email luoqf2000@126.comPurpose: To study the potential drug–drug interactions between simvastatin and vonoprazan and to provide the scientific basis for rational use of them in clinical practice.Methods: An incubation system was established with rat liver microsomes, and the main metabolite of vonoprazan M-I was detected by UPLC-MS/MS. The IC50 value of simvastatin was then calculated and its inhibitory mechanism against vonoprazan was also analyzed. Twelve SD rats were randomly divided into 2 groups, then they were given simvastatin or saline for 2 weeks continuously. On the day of the experiment, both groups were intragastrically administered with vonoprazan once, followed by the collection of blood at different time points. Then the plasma concentration of vonoprazan and M-I in rats were detected by UPLC-MS/MS.Results: In vitro experiments revealed that simvastatin could inhibit the metabolism of vonoprazan, and its inhibition type belonged to the mixed non-competitive and competitive inhibition model. In vivo experiments in rats demonstrated that the area under concentration time curve (AUC) of vonoprazan was decreased but the clearance (CLz/F) of it was increased in the simvastatin administrated group, as compared to those of the control group. However, M-I in simvastatin treated group exhibited the higher AUC and lower CLz/F values compared to those in the control group. These data indicated that multiple doses of simvastatin administration could reduce the plasma concentration of vonoprazan and accelerate its metabolic rate in rats.Conclusion: Simvastatin could inhibit the metabolism of vonoprazan in vitro but multiple doses of simvastatin exhibited the opposite effect In vivo. Altogether, our data indicated that an interaction existed between simvastatin and vonoprazan and additional cares might be taken when they were co-administrated in clinic.Keywords: vonoprazan, simvastatin, drug–drug interactions, liquid chromatography-tandem mass spectrometry, rat liver microsomes

Haw-Ming Huang,1,2 Ping-Han Wu,3 Po-Chien Chou,4 Wen-Tien Hsiao,5 Hsin-Ta Wang,4 Hsin-Pei Chiang,3 Chi-Ming Lee,6 Shwu-Huey Wang,6 Yu-Cheng Hsiao2,7 1School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; 2Graduate Institute of Biomedical Optomechatronics, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 3Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 4School of Organic and Polymeric, National Taipei University of Technology, Taipei, Taiwan; 5Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 6Core Facility Center, Office of Research and Development, Taipei Medical University, Taipei, Taiwan; 7Cell Physiology and Molecular Image Research Center, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, TaiwanCorrespondence: Yu-Cheng Hsiao; Ping-Han WuTaipei Medical University, No. 250, Wu-Hsing Street, Taipei, 11031, TaiwanTel +886-291-937-9783Fax +886 2 27362295Email ychsiao@tmu.edu.tw; gahwclbjwph@gmail.comIntroduction: It has been reported that low-molecular-weight hyaluronic acid (LMWHA) exhibits a potentially beneficial effect on cancer therapy through targeting of CD44 receptors on tumor cell surfaces. However, its applicability towards tumor detection is still unclear. In this regard, LMWHA-conjugated iron (Fe3O4) nanoparticles (LMWHA-IONPs) were prepared in order to evaluate its application for enhancing the T2* weighted MRI imaging sensitivity for tumor detection.Methods: LMWHA and Fe3O4 NPs were produced using γ-ray irradiation and chemical co-precipitation methods, respectively. First, LMWHA-conjugated FITC was prepared to confirm the ability of LMWHA to target U87MG cells using fluorescence microscopy. The hydrodynamic size distribution and dispersion of the IONPs and prepared LMWHA-IONPs were analyzed using dynamic light scattering (DLS). In addition, cell viability assays were performed to examine the biocompatibility of LMWHA and LMWHA-IONPs toward U87MG human glioblastoma and NIH3T3 fibroblast cell lines. The ability of LMWHA-IONPs to target tumor cells was confirmed by detecting iron (Fe) ion content using the thiocyanate method. Finally, time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging and in vitro magnetic resonance imaging (MRI) were performed to confirm the contrast enhancement effect of LMWHA-IONPs.Results: Florescence analysis results showed that LMWHA-FITC successfully targeted the surfaces of both tested cell types. The ability of LMWHA to target U87MG cells was higher than for NIH3T3 cells. Cell viability experiments showed that the fabricated LMWHA-IONPs possessed good biocompatibility for both cell lines. After co-culturing test cells with the LMWHA-IONPs, detected Fe ion content in the U87MG cells was much higher than that of the NIH3T3 cells in both thiocyanate assays and TOF-SIMs images. Finally, the addition of LMWHA-IONPs to the U87MG cells resulted in an obvious improvement in T2* weighted MR image contrast compared to control NIH3T3 cells.Discussion: Overall, the present results suggest that LMWHA-IONPs fabricated in this study provide an effective MRI contrast agent for improving the diagnosis of early stage glioblastoma in MRI examinations.Keywords: hyaluronic acid, Fe3O4 nanoparticles, TOF-SIMS, MRI

Jen-Ta Shih,1,2 Tsu-Te Yeh,1 Pei-Hung Shen,1 Chih-Chien Wang,1 Sheng-Hao Wang,1 Wu-Chien Chien,3– 6 Chi-Hsiang Chung,3– 5 Chia-Chun Wu1 1Department of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Graduate Institute of Injury Prevention and Control, College of Public Health, Taipei Medical University, Taipei, Taiwan; 3School of Public Health, National Defense Medical Center, Taipei, Taiwan; 4Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 5Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan; 6Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, TaiwanCorrespondence: Chia-Chun WuDepartment of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Road, Neihu Dist, Taipei City, 11472, TaiwanTel +886-953-086-492Fax +886-2-8792-7186Email orthopedicsintsgh@gmail.comPurpose: With recent advances in surgical techniques and instruments, orthopedic surgeons are better equipped to treat metastatic bone disease. There has also been considerable progress in the non-surgical treatment of cancers, specifically in improving the survival rate of patients with advanced cancer. However, it remains unclear whether surgical resection of a metastatic bone lesion poses additional risk to the survival of patients with advanced cancer.Patients and Methods: This study utilized data from the National Health Insurance Research Database (NHIRD) in Taiwan between 2000 and 2015. Patients aged ≥ 18 years, who had been recently diagnosed with bone metastases (BM), were enrolled and assigned to either the surgery or non-surgery groups. The demographic characteristics were analyzed, and the adjusted hazard ratios (aHR) of mortality were calculated using Cox regression analysis.Results: Of the 4,549,226 individuals in the inpatient database of the NHIRD, 83,536 patients with BM were enrolled in this study. Among them, 8802 underwent surgical resection for skeletal metastatic lesion and 66,098 did not. Altogether, 28,691 patients died, including 2798 (31.8%) in the surgery group and 25,893 (39.2%) in the non-surgery group. The aHR for mortality was 0.7-fold lower in the surgery group (p < 0.001).Conclusion: This study demonstrates that surgical resection of metastatic bone lesions did not pose any additional risk to survival outcomes. Thus, we believe that surgery, if indicated, could have a competitive role in the management of metastatic bone disease.Keywords: bone metastasis, surgical resection, mortality, bone resorption inhibitor

Wubet Birhan Yigzaw, 1 Jordi B Torrelles, 2 Shu-Hua Wang, 3 Belay Tessema 1 1Department of Medical Microbiology, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; 2Population Health Program, Texas Biomedical Research Institute, San Antonio, TX, USA; 3Department of Internal Medicine, Division of Infectious Diseases, College of Medicine, The Ohio State University, Columbus, OH, USACorrespondence: Wubet Birhan YigzawDepartment of Medical Microbiology, College of Medicine and Health Sciences, University of Gondar, P.O. Box: 196, Gondar, EthiopiaEmail yeshmebetessey@gmail.comBackground: Mycobacterium tuberculosis (Mtb) drug resistance is a key challenge in ending TB.Objective: The study aimed to determine anti-TB drug resistance and compare the discordance between phenotypic and genotypic drug-susceptibility testing (DST).Methods: Prospective enrollment and sputum collection from patients suspected of active pulmonary TB from May 2018 to December 2019 at the University of Gondar Hospital. Phenotypic DST study for streptomycin, isoniazid, rifampin, and ethambutol was done by MGIT 360 SIRE Kit. Genotypic resistance for isoniazid and rifampin was performed by MTBDRplus v2 line probe assay (LPA) and compared to phenotypic drug resistance.Results: A total of 376 patients, median age 32 years, and 53.7% male were enrolled. Mtb was isolated from 126 patients. 106/126 (84%) patients were newly diagnosed with TB and 20 patients with prior TB treatment. Seventy (66.0%) were susceptible to all anti‐TB drugs tested. Twenty-five (19.8%) of the isolates were resistant to isoniazid, 12 (9.5%) to rifampicin and six (5%) were multidrug resistant. Among previously treated TB patients, 4 (20.0%) and 5 (25.0%) were mono-resistant and poly-resistant, respectively. The sensitivity and specificity of LPA resistance for isoniazid were 94.4% and 100%, and for rifampin was 75.0% and 100%, respectively.Conclusion: The frequency of mono- and poly-drug resistance among both newly diagnosed and previously treated TB patients was high to the rest of the nation. MTBDRplus showed excellent concordance for isoniazid and rifampin. We concluded that DST should be performed for all patients to improve management and decrease spread of drug-resistant Mtb strains in the community.Keywords: Mycobacterium tuberculosis, diagnosis, drug resistance, MGIT, MTBDRplus

Diriba Alemayehu Gadisa,1 Shu-Hua Wang,2,3 Getnet Yimer4 1Pharmacy Department, College of Medicine and Health Sciences, Ambo University, Ambo, Ethiopia; 2Division of Infectious Diseases, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA; 3Ben Franklin TB Control Program, Columbus, OH, USA; 4Ohio State Global One Health Initiative, Office of International Affairs, The Ohio State University, Addis Ababa, EthiopiaCorrespondence: Diriba Alemayehu Gadisa 19 Tel +251915958190Email direalexphar@ymail.comPurpose: The study aimed to evaluate the quality of life patterns and the effects of AC and AC-T chemotherapy’s toxicities on QoL among Ethiopian women with breast cancer.Methods: QoL was measured at baseline and at every end of two cycles, for the median of 8 cycles among 146 breast cancer women on AC and AC-T chemotherapy, using EORTC QLQ-C30 and BR23 instruments. The effect of QoL score, socio-demographic, and clinical variables at baseline were adjusted for the effect of chemotherapy’s toxicities on QoL.Results: Overall QoL, all functional scales (except cognitive functioning, body image, future perspectives, and sexual functioning) and symptom scales (except dyspnea, insomnia, pain score, arm, and breast symptoms) of EORTC QLQ-C30 and BR23 deteriorated significantly both clinically and statistically, in particular, during the first two cycles of chemotherapy. After the end of cycle 2 or 4, except for cognitive, social functioning, and financial difficulties of the patients, almost all other QoL dimensions were improved towards pretreatment score by the end of cycle 8. In addition to age, educational status, and tumor stage, the Global Health Status (− 10.55≤B≤− 7.71, P≤ 0.013), and the functional scales (− 25.320≤B≤− 6.351, P≤ 0.033) of EORTC QLQ-C30 and BR23 were significantly affected at least by one of the AC and AC-T chemotherapy’s toxicity such as grade≥ 2 fatigue, dysgeusia, constipation, dry mouth, vomiting, oral mucositis, skin hyperpigmentation and/or peripheral neuropathy than their lower grade. Grade≥ 2 fatigue, dysgeusia, oral mucositis, constipation, peripheral neuropathy, anemia arthralgia/myalgia, dry mouth, diarrhea, constipation, and/or skin hyperpigmentation were positively predicted for the deterioration of symptoms scale of EORTC QLQ-C30 and BR23 (4.819≤B≤ 26.451, P≤ 0.043).Conclusion: Quality of life among Ethiopian breast cancer patients on AC and AC-T regimens significantly deteriorated particularly during the first two cycles of chemotherapy. In addition to the age, tumor stage and educational status of the patients, grade≥ 2 fatigue, dysgeusia, constipation, oral mucositis, dry mouth, peripheral neuropathy, and skin hyperpigmentation due to AC and AC-T chemotherapy were frequently associated with deterioration of different scales/items QoL. Hence, devising different strategies to improve the deteriorated QoL due to chemotherapy’s toxicities particularly during the first two cycles has paramount importance.Keywords: quality of life, deterioration, chemotherapy, toxicity, breast cancer, Ethiopia

Xiao-Long Liao, Zhong-Hua Wang, Xiu-Na Liang, Jun Liang, Xue-Biao Wei, Shou-Hong Wang, Wei-Xin Guo Department of Critical Care Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People’s Republic of ChinaCorrespondence: Shou-Hong Wang; Wei-Xin GuoDepartment of Critical Care Medicine, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Road 2, Guangzhou 510080, People’s Republic of ChinaTel/Fax +86-20-83827812Email gdwangshouhong@163.com; gguosumly@163.comPurpose: The relationship between circulating selenium and diabetes mellitus (DM) remains inconsistent. Therefore, the relationship between circulating selenium and DM was investigated in the present study.Patients and Methods: All participants (aged ≥ 18 years) were included from the National Health and Nutrition Examination Survey (NHANES) 1999– 2006. Selenium concentrations from the fasting serum samples were determined using inductively coupled mass spectrometry, then grouped into quartiles. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multivariate logistic regression analysis and the results were stratified by age and sex.Results: A total of 2,903 (61.9± 13.7 years old) participants (49.3% males) were enrolled, and 580 (19.97%) of them had DM. The mean levels of selenium were 136.4± 19.6 μg/L. Patients with DM (138.76± 20.02 vs 135.88± 19.44, P=0.002) had higher selenium levels compared to those without DM. The OR for DM was 1.12 (95% CI=1.01– 1.24; P=0.0270) for each 10 μg/L increment in selenium, and subjects in the highest quartile of selenium levels (> 147.00 uμg/L) had 2.82 (95% CI=1.55– 5.11; P=0.0007) times higher risk of DM compared to the lowest quartile of selenium levels. Subgroup analysis showed that selenium was independently associated with DM only in female aged < 65 years.Conclusion: Circulating selenium levels were positively associated with the odds of DM, but difference in sex and age.Keywords: diabetes mellitus, selenium, relationship

Chieh-Hsin Lin,1– 3 Hui-Ting Yang,4 Ping-Kun Chen,5,6 Shi-Heng Wang,7 Hsien-Yuan Lane2,8,9 1Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; 3School of Medicine, Chang Gung University, Taoyuan, Taiwan; 4School of Food Safety, Taipei Medical University, Taipei, Taiwan; 5School of Medicine, China Medical University, Taichung, Taiwan; 6Department of Neurology, China Medical University Hospital, Taichung, Taiwan; 7Department of Occupational Safety and Health, China Medical University, Taichung, Taiwan; 8Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan; 9Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung, TaiwanCorrespondence: Hsien-Yuan LaneDepartment of Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, TaiwanEmail hylane@gmail.comObjective: Behavioral and psychological symptoms of dementia (BPSD) are associated with poorer prognosis of dementia. A 24-week study demonstrated that sodium benzoate, a D-amino acid oxidase (DAAO) inhibitor, surpassed placebo in improving cognitive function in early-phase Alzheimer’s disease; however, benzoate did not excel placebo in another 6-week study on BPSD. The current study examined whether the precision medicine approach was able to identify specific individuals with BPSD who could benefit from benzoate treatment.Methods: In the randomized, double-blind, placebo-controlled, 6-week trial, 97 patients with BPSD were allocated to receive 250– 1500 mg/day of sodium benzoate or placebo. Cognitive function was measured by the Alzheimer’s disease assessment scale-cognitive subscale (ADAS-cog) and behavioral and psychological symptoms were mainly measured by Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD). DAAO level, amino acids (L-serine, D-serine, L-alanine, and D-alanine, glycine), and two antioxidants (catalase, superoxide dismutase) were assayed in peripheral blood.Results: After benzoate treatment, DAAO inhibition was correlated with ADAS-cog decrease (p = 0.034), while baseline DAAO level was correlated with baseline BEHAVE-AD score. Multiple linear regression analyses showed that cognitive improvement after benzoate treatment was correlated with DAAO decrease, female gender, younger age, BMI, baseline BPSD severity, and antipsychotic use.Conclusion: The finding suggests that sodium benzoate may have potential to benefit cognitive function in a fraction of BPSD patients after 6 weeks of treatment. Of note, the precision medicine approach may be helpful for identifying individuals who could respond to benzoate. More studies are warranted to confirm the preliminary findings.Trial Registration: The trial was registered online (https://clinicaltrials.gov/ct2/show/NCT02103673).Keywords: behavioral and psychological symptoms of dementia, BPSD, N-methyl-D-aspartate, D-amino acids oxidase, DAAO, inhibitor, sodium benzoate, precision medicine

Yunfang Zhou,1,* Shuanghu Wang,1,* Xuhua Ying,2 Yifan Wang,2 Peiwu Geng,1 Aiping Deng,3 Zhihong Yu3 1The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui, 2Cancer Institute of Integrative Medicine, Zhejiang Academy of Chinese Medicine, Hangzhou, 3Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China *These authors contributed equally to this work Abstract: Multidrug resistance (MDR) against chemotherapeutic agents has become one of the major obstacles to successful cancer therapy and MDR-associated proteins (MRPs)-mediated drug efflux is the key factor for MDR. In this study, a redox-responsive polymer based on dextran (DEX) and indomethacin (IND), which could reduce MRPs-mediated efflux of chemotherapeutics, was synthesized, and the obtained polymer could spontaneously form stable micelles with well-defined core-shell structure and a uniform size distribution with an average diameter of 50 nm and effectively encapsulate doxorubicin (DOX); the micelles contain a disulfide bridge (cystamine, SS) between IND and DEX (DEX-SS-IND). In vitro drug release results indicated that DEX-SS-IND/DOX micelles could maintain good stability in a stimulated normal physiological environment and promptly depolymerized and released DOX in a reducing environment. After incubating DEX-SS-IND/DOX micelles with drug-resistant tumor (MCF-7/ADR) cells, the intracellular accumulation and retention of DOX were significantly increased under the synergistic effects of redox-responsive delivery and the inhibitory effect of IND on MRPs. In vitro cytotoxicity showed that DEX-SS-IND/DOX micelles exhibited higher cytotoxicity against MCF-7/ADR cells. Moreover, DEX-SS-IND/DOX micelles showed significantly enhanced inhibition of tumor in BALB/c nude mice bearing MCF-7/ADR tumors and reduced systemic toxicity. Overall, the cumulative evidence indicates that DEX-SS-IND/DOX micelles hold significant promise for overcoming MDR for cancer therapy. Keywords: multidrug resistance, doxorubicin, indomethacin, redox-responsive, micelles, breast cancer

Yanjun Guo,1 Shuhui Wang,1 Bin Jiang,1 Jianle Li,1 Lei Liu,2 Jiawei Wang,2 Weiqin Zhao,1 Jianping Jia1 1Department of Neurology, Beijing Friendship Hospital, Capital Medical University. Beijing, China; 2Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing, China Background: Approximately 200 cases of mild encephalitis with reversible splenial (MERS) and deep cerebral white matter lesions have been reported since MERS was first defined in 2004. MERS occurs more frequently in children; in adults, only ~60 cases have been reported. Until now, only four cases of MERS in adults have been associated with Epstein–Barr virus (EBV). Case presentation: We report three adult cases of MERS associated with EBV infection in China. For all three patients, cranial magnetic resonance imaging (MRI) indicated solitary reversible splenial and/or perilateral ventricle white matter lesions with reduced diffusion. In the present report, all patients were adults presenting with high fever, headache, apathy, and confusion, as well as significant signs of meningeal inflammation. These symptoms peaked 10–14 days after disease onset, with serious hyponatremia (112–129 mmol/L), an elevated cerebrospinal fluid white blood cell count (80–380/mm3), and significantly increased protein levels (1,010–1,650 mg/dL). Cranial MRI indicated abnormal signal intensity in the splenium of corpus callosum and symmetrically reversible lesions scattered in the thalamus and deep cerebral white matter. The clinical symptoms tended to improve after ~10–14 days of antiviral treatment. However, these patients recovered more slowly than patients with viral meningitis. Conclusion: MERS associated with EBV infection in adults occurs less frequently but with more severe symptoms than in children. EBV infection should be considered for patients with MERS symptoms. MERS has a good prognosis. Keywords: mild encephalitis with reversible splenial lesions, Epstein-Barr virus, apathy, hyponatremia, corpus fluid

Tao Xu,1 Wei Liu,2 Suhang Wang,1 Zhengzhong Shao1 1State Key Laboratory of Molecular Engineering of Polymer, Advanced Materials Laboratory, Department of Macromolecular Science, 2Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University, Shanghai, People’s Republic of China Abstract: Polycations as gene carriers have attracted considerable attention over the past decade. Generally, polyplexes between polycations and deoxyribonucleic acid (DNA) are formed at low N/P ratios (the ratios of the numbers of nitrogen atoms in a polycation to the numbers of phosphorus atoms in DNA), but high transfection efficiency can only be obtained at much higher N/P ratios. Thus, many polycationic chains are still free in solution. In this study, we investigated the detailed functions of free polyethylenimine chains (PEI-F) and free N,N,N-trimethyl chitosan chains (TMC-F) using the same polyplex, ie, TMC polyplex (TMC-P), which has high stability in Dulbecco’s Modified Eagle’s Medium (DMEM). Meanwhile, PEI polyplex (PEI-P)/PEI-F was also evaluated rather than PEI-P/TMC-F because the stability of PEI-P is low in DMEM and, in the latter case, the TMC-F may replace the bound PEI chain in PEI-P to form TMC-P. The transfection results show that both TMC-F and PEI-F can significantly increase the transfection efficiency of TMC-P; however, PEI-F can upregulate the gene expression of TMC-P more efficiently than TMC-F. Further investigations on the endocytosis and intracellular trafficking show that PEI-P/PEI-F, TMC-P/PEI-F, and TMC-P/TMC-F exhibit similar cellular uptake efficiency. However, by shutting down the clathrin-mediated endocytosis or vacuolar proton pump, the transfection efficiency decreases in the order of PEI-P/PEI-F > TMC-P/PEI-F > TMC-P/TMC-F. These findings indicate that PEI-F and TMC-F may promote the transfection efficiency of the polyplex by affecting its cellular uptake pathway and intracellular trafficking. Keywords: cellular uptake pathway, intracellular trafficking, gene delivery, transfection efficiency, mechanism

Wan-Ju Hsieh,1 Chan-Jung Liang,1 Jen-Jie Chieh,4 Shu-Huei Wang,1 I-Rue Lai,1 Jyh-Horng Chen,2 Fu-Hsiung Chang,3 Wei-Kung Tseng,4–6 Shieh-Yueh Yang,4 Chau-Chung Wu,7 Yuh-Lien Chen11Institute of Anatomy and Cell Biology, College of Medicine, 2Department of Electrical Engineering, 3Institute of Biochemistry and Molecular Biology, National Taiwan University, Taipei, Taiwan; 4Institute of Electro-Optical Science and Technology, National Taiwan Normal University, Taipei, Taiwan; 5Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Taipei, Taiwan; 6Department of Medical Imaging and Radiological Sciences, I-Shou University, Taipei, Taiwan; 7Department of Internal Medicine and Primary Care Medicine, National Taiwan University Hospital, Taipei, TaiwanBackground: Active targeting by specific antibodies combined with nanoparticles is a promising technology for cancer imaging and detection by magnetic resonance imaging (MRI). The aim of the present study is to investigate whether the systemic delivery of antivascular endothelial growth factor antibodies conjugating to the surface of functionalized supermagnetic iron oxide nanoparticles (anti-VEGF-NPs) led to target-specific accumulation in the tumor.Methods: The VEGF expression in human colon cancer and in Balb/c mice bearing colon cancers was examined by immunohistochemistry. The distribution of these anti-VEGF-NPs particles or NPs particles were evaluated by MRI at days 1, 2, or 9 after the injection into the jugular vein of Balb/c mice bearing colon cancers. Tumor and normal tissues (liver, spleen, lung, and kidney) were collected and were examined by Prussian blue staining to determine the presence and distribution of NPs in the tissue sections.Results: VEGF is highly expressed in human and mouse colon cancer tissues. MRI showed significant changes in the T*2 signal and T2 relaxation in the anti-VEGF-NP- injected-mice, but not in mice injected with NP alone. Examination of paraffin sections of tumor tissues stained for the iron constituent of the NPs with Prussian blue revealed a strong blue reaction in the tumors of anti-VEGF-NP-treated mice, but only a weak reaction in mice injected with NPs. In both groups, at all time points, Prussian blue-stained liver and spleen sections showed only light staining, while stained cells were rarely detected in kidney and lung sections. Transmission electron microscopy showed that many more electron-dense particles were present in endothelial cells, tumor cells, and extracellular matrix in tumor tissues in mice injected with anti-VEGF-NPs than in NP-injected mice.Conclusion: These results demonstrated in vivo tumor targeting and efficient accumulation of anti-VEGF-NPs in tumor tissues after systemic delivery in a colon cancer model, showing that anti-VEGF-NPs have potential for use as a molecular-targeted tumor imaging agent in vivo.Keywords: nanoparticles, vascular endothelial growth factor, colon tumor, magnetic resonance imaging, transmission electron microscopy

Abstract The TAROGE-M radio observatory is a self-triggered antenna array on top of the ∼2700 m high Mt. Melbourne in Antarctica, designed to detect impulsive geomagnetic emission from extensive air showers induced by ultra-high energy (UHE) particles beyond 1017 eV, including cosmic rays, Earth-skimming tau neutrinos, and particularly, the “ANITA anomalous events” (AAE) from near and below the horizon. The six AAE discovered by the ANITA experiment have signal features similar to tau neutrinos but that hypothesis is in tension either with the interaction length predicted by Standard Model or with the flux limits set by other experiments. Their origin remains uncertain, requiring more experimental inputs for clarification. The detection concept of TAROGE-M takes advantage of a high altitude with synoptic view toward the horizon as an efficient signal collector, and the radio quietness as well as strong and near vertical geomagnetic field in Antarctica, enhancing the relative radio signal strength. This approach has a low energy threshold, high duty cycle, and is easy to extend for quickly enlarging statistics. Here we report experimental results from the first TAROGE-M station deployed in January 2020, corresponding to approximately one month of livetime. The station consists of six receiving antennas operating at 180-450 MHz, and can reconstruct source directions of impulsive events with an angular resolution of ∼0.3°, calibrated in situ with a drone-borne pulser system. To demonstrate TAROGE-M's ability to detect UHE air showers, a search for cosmic ray signals in 25.3-days of data together with the detection simulation were conducted, resulting in seven identified candidates. The detected events have a mean reconstructed energy of 0.95-0.31+0.46 EeV and zenith angles ranging from 25° to 82°, with both distributions agreeing with the simulations, indicating an energy threshold at about 0.3 EeV. The estimated cosmic ray flux at that energy is 1.2-0.9+0.7 × 10-16 eV-1 km-2 yr-1 sr-1, also consistent with results of other experiments. The TAROGE-M sensitivity to AAEs is approximated by the tau neutrino exposure with simulations, which suggests comparable sensitivity as ANITA's at around 1 EeV energy with a few station-years of operation. These first results verified the station design and performance in a polar and high-altitude environment, and are promising for further discovery of tau neutrinos and AAEs after an extension in the near future.

The ARIANNA neutrino detector, located at sea-level on the Ross Ice Shelf, Antarctica, consists of 200 autonomous and independent detector stations separated by 1 kilometer in a uniform triangular mesh, and serves to inform the planning of the future projects. The primary science mission of ARIANNA is to search for sources of neutrinos with energies greater than 1017 eV, complementing the reach of IceCube and other neutrino telescopes that focus on lower energies. An ARIANNA observation of a neutrino source would provide strong insight into the enigmatic sources of cosmic rays. ARIANNA observes the radio emission from high energy neutrino interactions in the Antarctic ice. Among radio based concepts under current investigation, ARIANNA would uniquely survey the vast majority of the southern sky at any instant in time, and an important region of the northern sky, by virtue of its location on the surface of the Ross Ice Shelf at Moore’s Bay. The broad sky coverage is specific to the Moore’s Bay site, providing capabilities to observe explosive sources from unknown directions. The ARIANNA architecture is designed to measure the angular direction to within 4 degrees for every neutrino candidate, which too plays an important role in the pursuit of multi-messenger observations of astrophysical sources. The sea level location reduces the impact of a potentially serious background associated with the cores of cosmic ray air showers striking the ice surface, generating radio pulses which are similar to those expected from neutrino events. Reflecting layers at the bottom or within the ice sheet (which are known to exist in thick ice sheets) might create a troublesome rate of background events, provided the reflection coefficients are large enough, that arrive at the detector from the same directions as neutrinos.

The ARIANNA detector is designed to detect neutrinos of energies above 1016 eV. Due to the similarities in generated radio signals, cosmic rays are often used as test beams for neutrino detectors. Some ARIANNA detector stations are equipped with antennas capable of detecting air showers. The radio emission properties of air showers are well understood, and the polarization of the radio signal can be predicted from arrival direction with high precision. For this reason, cosmic rays can be used as a proxy to assess the reconstruction capabilities of the ARIANNA neutrino detector. We report on dedicated efforts of reconstructing the polarization of cosmic-ray radio pulses. A total of 148 cosmic rays are identified from over 90,000 triggered events collected between Nov 21, 2018 and Mar 15, 2019. A cut was put on these events requiring them to have a signal-to-noise (SNR) ratio of at least 4.5 in all upward-facing channels. This was to improve the performance of arrival direction and polarization reconstruction algorithms. Polarization of these cosmic rays were reconstructed with a resolution of 3.5 degrees (68% containment), which agrees with the expected value we obtained from simulation. Furthermore, if we subselect events with zenith angle greater than 70 deg, the contribution to polarization of Askaryan effect is reduced, which reduces the error in the predicted polarization. With limited statistics, we find the polarization uncertainty is reduced to 1.3 deg (68% containment).

High energy neutrinos (E >1017 eV) are detected cost-efficiently via the Askaryan effect in ice, where a particle cascade induced by the neutrino interaction produces coherent radio emission that can be picked up by antennas installed below the surface. A good knowledge of the near surface ice (aka firn) properties is required to reconstruct the neutrino properties. In particular, a continuous monitoring of the snow accumulation (which changes the depth of the antennas) and the index-of-refraction profile are crucial for an accurate determination of the neutrino’s direction and energy. We present an in-situ calibration system that extends the radio detector station with a radio emitter to continuously monitor the firn properties by measuring time differences of direct and reflected (off the surface) signals (D’n’R). We optimized the station layout in a simulation study and quantified the achievable precision. We present 14 months of data of the ARIANNA detector on the Ross Ice Shelf, Antarctica, where a prototype of this calibration system was successfully used to monitor the snow accumulation with unprecedented precision of 1 mm. We explore and test several algorithms to extract the D’n’R time difference from noisy data (including deep learning). This constitutes an in-situ test of the neutrino vertex distance reconstruction using the D’n’R technique which is needed to determine the neutrino energy.

The ARIANNA experiment is a proposed Askaryan detector designed to record radio signals induced by neutrino interactions in the Antarctic ice. Because of the low neutrino flux at high energies, the physics output is limited by statistics. Hence, an increase in sensitivity significantly improves the interpretation of data and offers the ability to probe new parameter spaces. The trigger thresholds are limited by the rate of triggering on unavoidable thermal noise fluctuations. The real-time thermal noise rejection algorithm enables the thresholds to be lowered substantially and increases the sensitivity by up to a factor of two compared to the current ARIANNA capabilities. A deep learning discriminator, based on a Convolutional Neural Network (CNN), is implemented to identify and remove a high percentage of thermal events in real time while retaining most of the neutrino signals. We describe a CNN that runs on the current ARIANNA microcomputer and retains 95% of the neutrino signals at a thermal rejection factor of 105. Finally, the experimental verification from lab measurements are conducted.

A radio-frequency polarization measurement by the ARIANNA surface station was performed using a residual hole from the South Pole Ice Core (SPICEcore) Project. Radio pulses were emitted from a transmitter located down to 1.7 km below the snow surface. After deconvolving the raw signals for the detector response and attenuation from propagation through the ice, the signal pulses show no significant distortion and agree with a reference measurement of the emitter made in an anechoic chamber. The direction to transmitted radio pulse was measured with an angular resolution of 0.37 degree [statistical error]. For polarization, the statistical error of the polarization vector is depth dependent and below 1 degree. In addition, a slowly-varying systematic variation is observed as a function of depth with an rms error of 2.7 degrees. Neither the direction or polarization measurement show a significant offset as a function of depth relative to expectation. We also report on the results of a simulation study of the ARIANNA neutrino direction and energy resolution. The software tool NuRadioMC was used to reconstruct the polarization and viewing angle to determine the neutrino direction. Multiple models of Askaryan radiation and detector sites along with a range of neutrino energies were evaluated. The neutrino space angle resolution was determined to be below 3 degrees, which is comparable to the systematic polarization uncertainty. Therefore it is expected that the polarization resolution, which is the dominant contribution to the neutrino space angle resolution, will be improved in future studies by determining and eliminating systematic effects.

The sources of ultra-high energy (UHE) cosmic rays, which can have energies up to 1020 eV, remain a mystery. UHE neutrinos may provide important clues to understanding the nature of cosmic-ray sources. ARIANNA aims to detect UHE neutrinos via radio (Askaryan) emission from particle showers when a neutrino interacts with ice, which is an efficient method for neutrinos with energies between 1016 eV and 1020 eV. The ARIANNA radio detectors are located in Antarctic ice just beneath the surface. Neutrino observation requires that radio pulses propagate to the antennas at the surface with minimum distortion by the ice and firn medium. Using the residual hole from the South Pole Ice Core Project, radio pulses were emitted from a transmitter located up to 1.7 km below the snow surface. By measuring these signals with an ARIANNA surface station, the angular and polarization reconstruction abilities are quantified, which are required to measure the direction of the neutrino. After deconvolving the raw signals for the detector response and attenuation from propagation through the ice, the signal pulses show no significant distortion and agree with a reference measurement of the emitter made in an anechoic chamber. Furthermore, the signal pulses reveal no significant birefringence for our tested geometry of mostly vertical ice propagation. The origin of the transmitted radio pulse was measured with an angular resolution of 0.37◦ indicating that the neutrino direction can be determined with good precision if the polarization of the radio-pulse can be well determined. In the present study we obtained a resolution of the polarization vector of 2.7◦. Neither measurement show a significant offset relative to expectation.

The primary mission of the ARIANNA ultra-high energy neutrino telescope is to uncover astrophysical sources of neutrinos with energies greater than 1016 eV. A pilot array, consisting of seven ARIANNA stations located on the surface of the Ross Ice Shelf in Antarctica, was commissioned in November 2014. We report on the search for astrophysical neutrinos using data collected between November 2014 and February 2019. A straight-forward template matching analysis yielded no neutrino candidates, with a signal efficiency of 79%. We find a 90% confidence upper limit on the diffuse neutrino flux of E2Φ=1.7× 10-6 GeV cm-2s-1sr-1 for a decade wide logarithmic bin centered at a neutrino energy of 1018,eV, which is an order of magnitude improvement compared to the previous limit reported by the ARIANNA collaboration. The ARIANNA stations, including purpose built cosmic-ray stations at the Moore's Bay site and demonstrator stations at the South Pole, have operated reliably. Sustained operation at two distinct sites confirms that the flexible and adaptable architecture can be deployed in any deep ice, radio quiet environment. We show that the scientific capabilities, technical innovations, and logistical requirements of ARIANNA are sufficiently well understood to serve as the basis for large area radio-based neutrino telescope with a wide field-of-view.

The measurement of ultra-high energy (UHE) neutrinos (E > 1016 eV) opens a new field of astronomy with the potential to reveal the sources of ultra-high energy cosmic rays especially if combined with observations in the electromagnetic spectrum and gravitational waves. The ARIANNA pilot detector explores the detection of UHE neutrinos with a surface array of independent radio detector stations in Antarctica which allows for a cost-effective instrumentation of large volumes. Twelve stations are currently operating successfully at the Moore's Bay site (Ross Ice Shelf) in Antarctica and at the South Pole. We will review the current state of ARIANNA and its main results. We report on a newly developed wind generator that successfully operates in the harsh Antarctic conditions and powers the station for a substantial time during the dark winter months. The robust ARIANNA surface architecture, combined with environmentally friendly solar and wind power generators, can be installed at any deep ice location on the planet and operated autonomously. We report on the detector capabilities to determine the neutrino direction by reconstructing the signal arrival direction of a 800 m deep calibration pulser, and the reconstruction of the signal polarization using the more abundant cosmic-ray air showers. Finally, we describe a large-scale design – ARIA – that capitalizes on the successful experience of the ARIANNA operation and is designed sensitive enough to discover the first UHE neutrino.

Ultra high energy neutrinos (Eν > 1016.5eV) are efficiently measured via radio signals following a neutrino interaction in ice. An antenna placed1(15 m) below the ice surface will measure two signals for the vast majority of events (90% at Eν=1018 eV): a direct pulse and a second delayed pulse from a reflection off the ice surface. This allows for a unique identification of neutrinos against backgrounds arriving from above. Furthermore, the time delay between the direct and reflected signal (D'n'R) correlates with the distance to the neutrino interaction vertex, a crucial quantity to determine the neutrino energy. In a simulation study, we derive the relation between time delay and distance and study the corresponding experimental uncertainties in estimating neutrino energies. We find that the resulting contribution to the energy resolution is well below the natural limit set by the unknown inelasticity in the initial neutrino interaction. We present an in-situ measurement that proves the experimental feasibility of this technique. Continuous monitoring of the local snow accumulation in the vicinity of the transmit and receive antennas using this technique provide a precision of (1 mm) in surface elevation, which is much better than that needed to apply the D'n'R technique to neutrinos.

Matrix Metalloproteinase-9 (MMP9) degrades the Extracellular Matrix (ECM), participates in mammary gland remodeling, and inhibits mammary epithelial cell apoptosis in goats. To investigate the transcriptional regulatory mechanism of the MMP9 promoter region, we analyzed the expression pattern of MMP9 in dairy goats by qRT-PCR and cloned the promoter region by PCR. Deletion analysis indicated that the MMP9 gene core promoter region was located upstream of the transcription start site in the -715 bp to -926 bp region. We predicted three Specificity protein 1 (Sp1) binding sites in the MMP9 core promoter region, and performed targeted mutations on these three sites. The c.1863 G> A mutation in the MMP9 gene increased the promoter transcriptional activity and may be associated with an additional Serum Response Factor (SRF) transcription factor-binding site. Association analysis revealed that c.1863 G> A was significantly associated with milk fat percentage in dairy goats, which was significantly higher in goats with the AG genotype (4.71±0.02%) than in goats with the GG genotype (4.61±0.05%). This study lays a foundation for subsequent analysis of the transcriptional regulatory mechanism of MMP9 and exploration of its biological functions. [ABSTRACT FROM AUTHOR]

In Older to promote the innovation of knitted fabric structure and surface effect, the semi-three-dimensional geometric origami force was taken as the research object, jlid its internal structure was deduced into plane form by analyzing the foliation principle of semi-three-dimensional form and using planarization design thinking. With the help of Ml Plus paein design software of STOLL company and CMS 502 computer flat knitting machine, the one-side and two-side pseupro-semi-three-dimensional geonfetric origami fabric was realized. The machine parameters, yarn selection, structure design and plate making were discussed in detail, and the influence of different structure and yarn material on the smart effect of the fabric was evaluated. The results show that using the double-sided structure design and yarn with high elasticity and hardness can better shape the semi-three-dimensional geometric origami. In addition, the flexible use of needle arrangement, yarn material and parameter changes in the design can form different geometric origami patterns of knitted fabrics, which provides a useful reference for the innovative design of fabric structure. [ABSTRACT FROM AUTHOR]

The aerosol radiative effect can be modulated by the vertical distribution and optical properties of aerosols, particularly when aerosol layers are decoupled. Direct aerosol radiative effects over the northern South China Sea (SCS) were assessed by incorporating an observed data set of aerosol optical properties obtained from the Seven South East Asian Studies (7-SEAS)/Dongsha Experiment into a radiative transfer model. Aerosol optical properties for a two-layer structure of aerosol transport were estimated. In the radiative transfer calculations, aerosol variability (i.e., diversity of source region, aerosol type, and vertical distribution) for the complex aerosol environment was also carefully quantified. The column-integrated aerosol optical depth (AOD) at 500nm was 0.1-0.3 for near-surface aerosols and increased 1-5 times in presence of upper layer biomass-burning aerosols. A case study showed the strong aerosol absorption (single-scattering albedo (ω) ≈ 0.92 at 440nm wavelength) exhibited by the upper layer when associated with predominantly biomass-burning aerosols, and the ω (≈0.95) of near-surface aerosols was greater than that of the upper layer aerosols because of the presence of mixed type aerosols. The presence of upper level aerosol transport could enhance the radiative efficiency at the surface (i.e., cooling) and lower atmosphere (i.e., heating) by up to -13.7 and +9.6Wm-2 per AOD, respectively. Such enhancement could potentiallymodify atmospheric stability, can influence atmospheric circulation, as well as the hydrological cycle over the tropical and low-latitude marginal northern SCS.

Cold regions exhibit a high prevalence of cardiovascular disease, particularly acute myocardial infarction (AMI), which is one of the leading causes of death associated with cardiovascular conditions. Cardiovascular disease is closely linked to the abnormal expression of long non-coding RNA (lncRNA). This study investigates whether circulating levels of lncRNA cardiac conduction regulatory RNA (CCRR) could serve as a biomarker for AMI.

Background Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disorder that primarily affects the vasculature and exhibits a broad spectrum of clinical manifestations. There is a paucity of detailed literature on its clinical characteristics. Objective This study aims to deepen the understanding of HHT's clinical aspects by documenting the presentations, management, and outcomes of 30 patients diagnosed with the condition, thereby improving recognition and treatment approaches among healthcare professionals. Methods A retrospective review was conducted on 30 HHT cases treated at Peking Union Medical College Hospital from December 2012 to September 2023, focusing on analyzing their clinical features, therapeutic interventions, and follow-up outcomes. Results The study included 8 males and 22 females, with a mean onset age of 20.0 years (range 10.5-34.0 years) and an average disease duration of 19.5 years (range 7.8-26.0 years). Epistaxis was universally present (100.0%), skin and mucosal telangiectasia were noted in 27 patients (90.0%), and 28 (93.3%) exhibited involvement of internal organs, including liver in 24 (80.0%), lungs in 15 (50.0%), gastrointestinal tract in 5 (16.7%), and brain in 3 (10.0%). Additionally, pulmonary hypertension was observed in 17 (56.7%) and iron deficiency anemia in 15 (50.0%). Genetic analysis in 15 patients identified ACVRL1 mutations in 12, ENG mutations in 2, and one patient with both. Beyond routine symptomatic care, some patients underwent targeted medical or interventional treatments, with the majority showing clinical improvement. Conclusion HHT is a systemic disorder affecting multiple organs, with frequent liver and occasional brain involvement. It commonly leads to serious complications such as pulmonary hypertension and iron deficiency anemia. Detailed patient history, thorough examinations, targeted screening of visceral vessels, and genetic testing are essential for early diagnosis and effective management in suspected cases.

[Purposes] This research is conducted to exploret the roof movement law of double roadway arrangement in thick coal seam and the abutment pressure distribution mechanism of surrounding rock. [Methods] The roof cuttings of single roadway in belt channeling and return air channeling in Gucheng N1302 face were taken as the engineering research objects to achieve effective pressure relief in double roadway. Theoretical analysis, field tests, and numerical simulation were used to investigate the mechanism of roof cutting and pressure relief on double roadway arrangements. [Findings] The results show that, according to theoretical calculation, the range of the internal stress field increases obviously after roof cutting, which can effectively reduce the stress of the belt along the groove. Field tests show that the deformation of the surrounding rock is significantly reduced when the top cutting height is 20 m, but the key layer of the upper level turns ahead of time, increasing the floor heave during the service of the return air channeling channel. The numerical simulation results show that the vertical stress of the coal wall is not affected by increasing the cutting height when the upper key layer is not cut off. While when the upper key layer is cut off, the vertical stress of the coal wall in the return air channeling channel decreases obviously. When the cutting height of the top is fixed, changing the width of the coal pillar between lanes can control the stress of the return air channeling.

"Wide-awakeness"is the core proposition in Maxine Green's philosophy.The proposal of"wide-awakeness"is based on the reflection of the harm of technical rationality, the correction of excessive pursuit of the value of educational tools, and the vigilance of the numbness of "given" and the neglect of self-existence in teachers'work and life.This concept, borrowed from the field of sociology, aims to describe the ideal state of consciousness of teachers who maintain a high degree of consciousness tension and pay full attention to educational life, taking into account the dual demands of teachers'self-consciousness and identity consciousness.For teachers, the realization of "wide-awakeness"has the dual value of boosting personal growth and role growth: it can not only help teachers consciously change the status quo and pursue a better life, but also encourages teachers to transcend their own knowledge and thinking limitations, innovate teaching content and methods, and help students develop their personality and play their potential.

A finite element analysis model was employed to analyze the heat conduction behavior of glass fiber/metal (stainless steel, aluminum, or oxygen-free copper) composite materials under a constant thermal load of 100°C on the metal surface, i.e., the temperature distribution after reaching thermal equilibrium. By comparing and analyzing the effects of different metal materials, different air convection heat transfer capabilities, and different metal phase thicknesses, the heat transfer mechanism is elaborated. The results indicate that the metal with stronger heat conduction capacity induces more uniform temperature distribution, while the temperature uniformity on the fiber is relatively worse. Besides, with the increase of the air convection heat transfer coefficient, the temperature on the fiber phase shows a significant downward trend, however, the impact on the metal phase remains limited. In addition, the metal thickness primarily affects the weight or rigidity of the composite material, with minimal impact on temperature distribution.

Parkinson’s disease (PD) is a chronic degenerative disorder of the nervous system. Lipids, as fundamental components of cells, are integral to both structural functions and physiological roles. They are essential for the development of brain structures and the maintenance of normal physiological activity in nerve cells. Lipid metabolism is intricately involved in the pathological progression of PD. This review primarily summarizes the abnormalities in lipid metabolism observed in PD, the resultant pathological damage, and lipid metabolism-based therapeutic strategies. Additionally, it discusses recent advancements in related drug research and explores future prospects in this field.

Most patients are at advanced stages when they are diagnosed with hepatocellular carcinoma, leading to poor prognosis and a low 5-year survival rate. Serological markers, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography, and liver biopsy are the common clinical diagnostic techniques for liver cancer. Effective interventions in the early stage will be beneficial to improve the prognosis of liver cancer patients and reduce the global burden. Therefore, it is urgent to develop new diagnostic methods to improve the diagnosis and management of liver cancer. Nanotechnology has become a new frontier subject in medical detection along with the application of nanomaterials in the manufacture of drug carriers, diagnostic tools, and therapeutic devices. Many studies have shown that nanoparticles (NPs) can be applied to the clinical diagnosis of liver cancer in combination with existing technologies, providing a new method for the early diagnosis of liver cancer. In this review, we elaborate on the theoretical basis and characteristics of NPs in the diagnosis of liver cancer, and the research progress and prospects of NPs in the diagnosis of liver cancer are summarized.

Abstract Accurate carbon price forecasts are crucial for policymakers and enterprises to understand the dynamics of carbon price fluctuations, enabling them to formulate informed policies and investment strategies. However, due to the non-linear and non-stationary nature of carbon price, traditional models often struggle to achieve high prediction accuracy. To address this challenge, this study proposes a novel integrated prediction framework designed to enhance forecast accuracy. First, the carbon price series is decomposed into a series of smoother subsequences using fast iterative filtering (FIF). Subsequently, an integrated prediction model, AM-TCN-LSTM, is constructed, incorporating the attention mechanism (AM), temporal convolutional networks (TCN), and long short-term memory (LSTM) neural networks. The attention mechanism adaptively captures complex features from multiple factors, while the TCN-LSTM efficiently extracts temporal features from the sequences. Finally, the results from each subsequence are aggregated to generate the final prediction. Five carbon markets in china: Guangdong, Hubei, Shenzhen, Beijing, and Shanghai were selected to verify the validity of the proposed model. Various comparative models and evaluation metrics were employed to assess performance. The results demonstrate that: (1) the TCN-LSTM model achieves higher prediction accuracy compared to single models. (2) FIF is a more effective decomposition method with superior performance compared to EMD-based methods. (3) The proposed model exhibits the highest predictive capability, with MAE values of 0.0964, 0.1403, 1.9476, 2.0848, and 0.5029 for the five carbon markets, significantly outperforming comparison models. (4) The attention mechanism effectively captures the influence of multiple factors on carbon price, particularly within the short-term components.

Objective To research new methods and materials for cranioplasty in children with various types of skull defects. Methods and Results A total of 40 childrens with different locations, sizes and reasons of skull defects underwent surgery using 3 classes of homogeneous yet heterogeneous biomimetic hydroxyapatite collagen bone materials developed by Tsinghua University. These include porous mineralized collagen scaffolds (pMC), compact mineralized collagen scaffolds (cMC), and biphasic mineralized collagen composite scaffolds (bMC). Cranioplasty was successful in all cases, with no serious postoperative complications and good recovery outcomes. After 3 months to one year of follow-up, there was no displacement of the implants, the shape of the head was normal, the incisions healed well. Reexamination CT showed that the biomimetic hydroxyapatite collagen bone material implants were not shifted, and imaging fusion was partially achieved. The pMC CT HU-value was 300-400 HU, and the cMC CT HU - value was 700-900 HU, and the CT HU - value was close to normal bone tissue over time. Conclusions The use of different types of biomimetic hydroxyapatite collagen composites allows for personalized cranial reconstruction based on individual needs, and has been proven to possess good bio- compatibility and osteoinductive capacity. This approach is thus promising for research and clinical applications, with significant value.

The suppression of vibration and noise has always been an important issue in engineering，and metamaterials have shown significant application value in vibration and noise reduction. In this paper，a novel hollow starshaped chiral metamaterial is designed by incorporating chiral structural characteristics into traditional hollow starshaped metamaterials and further evolves it into a solid star-shaped chiral metamaterial. The bandgap formation mechanism is analyzed through vibration mode analysis，and the effects of different structural parameters on the bandgap are studied. The propagation characteristics of elastic waves in the structure are investigated through dispersion surfaces，wave propagation direction，group velocity，and phase velocity. Finally，the transmission characteristics of finite periodic structures are studied. The results show that the solid star-shaped chiral metamaterial can generate an ultra-wide bandgap with a width of 5 116 Hz. The bandgap formation is mainly due to the rotational vibrations of the concave stars and ligaments dissipating the energy of elastic waves. Additionally，a decrease in the inner concave angle α and an increase in the angle θ between the ligaments and the horizontal direction result in a wider largest bandgap. The finite periodic structure can generate significant displacement amplitude attenuation within the bandgap range. This novel metamaterial has excellent vibration isolation performance.