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Adipose derived stem cells (ADSCs) have been increasingly explored for use in cell-based therapy against ischemic diseases. However, unsatisfactory angiogenesis limits the therapeutic efficacy. Netrin-1, a known axon guidance molecule, improves neovascularization in the ischemic region. Thus, our study was performed to evaluate the potential effect of Netrin-1 on the angiogenic behaviors of human ADSCs (hADSCs). hADSCs acquired from human abdominal adipose tissue were modified by liposome transfection of Netrin-1 plasmid, and the proliferation of hADSCs was determined by Cell Counting Kit-8 (CCK-8) assay. The transcript levels of pro-invasive proteins such as matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP-9), were measured to test migratory and invasive capabilities, and the levels of vascular endothelial growth factors were assayed to monitor angiogenic activity. Our results showed that Netrin-1 overexpression enhanced the proliferation of hADSCs, and promoted the migration and invasion of hADSCs, as indicated by increased levels of MMP-2 and MMP-9. Furthermore, Netrin-1 overexpression increased the expression of vascular endothelial growth factor and placental growth factor in hADSCs. Our results highlighted the possibility that genetic modification of hADSCs by Netrin-1 overexpression might be beneficial for cell transplantation therapy against ischemic diseases.

Lassa virus (LASV) is a significant human pathogen causing hemorrhagic fever in West Africa. Increased traveling around the world raises the risk of imported cases to other countries.

Abstract Purpose To determine obstructive sleep apnea (OSA) phenotypes using cluster analysis including variables of sleep perception and sleep quality and to further explore factors correlated with poor sleep quality in different clusters. Methods This retrospective study included patients with OSA undergoing polysomnography (PSG) between December 2020 and April 2022. Two-step cluster analysis was performed to detect distinct clusters using sleep perception variables including discrepancy in total sleep time (TST), sleep onset latency (SOL), and wakefulness after sleep onset (WASO); objective TST, SOL, and WASO; and sleep quality. One-way analysis of variance or chi-squared tests were used to compare clinical and PSG characteristics between clusters. Binary logistic regression analyses were used to explore factors correlated with poor sleep quality. Results A total of 1118 patients were included (81.6% men) with mean age ± SD 43.3 ± 13.1 years, Epworth sleepiness score, 5.7 ± 4.4, and insomnia severity index 3.0 ± 2.4. Five distinct OSA clusters were identified: cluster 1 (n = 254), underestimated TST; cluster 2 (n = 158), overestimated TST; cluster 3 (n = 169), overestimated SOL; cluster 4 (n = 155), normal sleep discrepancy and poor sleep quality; and cluster 5 (n = 382), normal sleep discrepancy and good sleep quality. Patients in cluster 2 were older, more commonly had hypertension, and had the lowest apnea–hypopnea index and oxygen desaturation index. Age and sleep efficiency were correlated with poor sleep quality in clusters 1, 2, and 5, and also AHI in cluster 2. Conclusion Subgroups of patients with OSA have different patterns of sleep perception and quality that may help us to further understand the characteristics of sleep perception in OSA and provide clues for personalized treatment.

To investigate the clinical value of measuring pancreatic fat fraction using dual-energy computed tomography (DECT) in association with type 2 diabetes mellitus (T2DM).This retrospective study included patients who underwent abdominal DECT between September 2021 and July 2022. The fat fractions in the head, body, and tail of the pancreas were calculated using fat maps generated from unenhanced DECT images, and CT values were measured at the same locations. The intraclass correlation coefficient (ICC) was used to analyze the reproducibility of measurements from two observers. Diagnostic performance was assessed using receiver operating characteristic curves.Seventy-eight patients, including 45 T2DM patients and 33 controls, were enrolled. The fat fractions of the pancreas were significantly higher in the T2DM group than in the control group (pancreatic head: 8.4 ± 6.3 % vs 5.1 ± 3.9 %; pancreatic body: 4.8 ± 4.0 % vs 2.7 ± 3.9 %; and pancreatic tail: 5.3 ± 3.2 % vs 2.7 ± 2.9 %, all p 0.05). And the CT values of the pancreas were significantly lower in the T2DM group than in the control group (pancreatic head: 41.1 ± 8.5 HU vs 45.7 ± 4.6 HU; pancreatic body: 44.4 ± 5.0 HU vs 47.4 ± 3.7 HU; and pancreatic tail: 44.5 ± 5.0 HU vs 47.6 ± 3.2 HU, all p 0.05). The fat fraction of the pancreatic tail was the best indicator for distinguishing T2DM patients from the controls (area under the curve: 0.716 (95 % CI: 0.601, 0.832), sensitivity: 64.4 % (95 % CI: 48.7 %, 77.7 %), and specificity: 78.8 % (95 % CI: 60.6 %, 90.4 %)).The DECT fat fractions of the pancreas could be a valuable additional parameter in the detection of T2DM.

Objective: In this study，we aimed to identify differentially expressed heat shock proteins (HSPs) profile in the villi and decidua from early missed abortion(EMA) patients. Methods: By using high-throughput and high-precision Parallel Reaction Monitoring (PRM)-based targeted proteomics technique, this study studied the expressions of HSPs in villi and decidua of 10 EMA patients and 10 controls. Meanwhile, the expressions of 3 HSPs in villi of another 22 EMA patients and 22 controls were verified with Western blotting and immunohistochemistry (IHC). Results:Compared with the control group, there were potential differences in the expressions of 16 HSPs and 42 polypeptides in human villi and decidua. Among them, HSP90AB1, HSPD1 and HSPA13 were down-regulated in expressions in villi of EMA patients, with a statistically significant difference, which was consistent with the verification results of Western blot and IHC. Conclusion: Using PRM- based targeted proteomics technique, this study for the first time screens and quantitatively analyzes the expression profile of HSPs in villi and decidua of patients with EMA. The significant down-regulated expressions of HSP90AB1, HSPD1 and HSPA13 are discovered to have a potentially intimate association with the occurrence of EMA. Findings in our study may provide novel potential research targets related to HSPs for the pathogenesis, prevention and treatment of EMA.

Objective This prospective study assessed the risk of developing rotator cuff syndrome (RCS) with separate or specific combinations of biomechanical exposures measures, controlling for individual confounders. Background Compared with other musculoskeletal disorders, rates of work-related shoulder musculoskeletal disorders have been declining more slowly. Method We conducted up to 2 years of individual, annual assessments of covariates, exposures, and health outcomes for 393 U.S. manufacturing and healthcare workers without RCS at baseline. Task-level biomechanical exposures assessed exposure to forceful exertions (level, exertion rates, duty cycles), vibration, and upper arm postures (flexion, abduction). Hazard ratios (HRs) were calculated with Cox proportional hazard models. Results We observed 39 incident RCS cases in 694 person-years (incidence rate = 5.62 per 100 person-years). Adjusting for confounders, we found increased risk of incident RCS associated with forceful hand exertions per minute for three upper arm posture tertiles: flexion ≥45° (≥28.2% time, HR = 1.11, CI [1.01, 1.22]), abduction ≥30° (11.9–21.2%-time, HR = 1.18, CI [1.04, 1.34]), and abduction >60° (≥4.8% time, HR = 1.16, CI [1.04, 1.29]). We failed to observe statistically significant effects for other interactions or any separate measures of biomechanical exposure. Conclusion This study highlights the importance of assessing combinations of exposure to forceful repetition and upper arm elevation when developing interventions for preventing RCS. Application Based on these results, interventions that reduce exposure to forceful repetition (i.e., lower force levels and/or slower exertion rates) may reduce the risk of RCS, especially when upper arm elevation cannot be avoided.

PurposeThe purpose of this paper is to explore whether the out-of-sample model bias plays an important role in predicting volatility.Design/methodology/approachUnder the heterogeneous autoregressive realized volatility (HAR-RV) framework, we analyze the predictive power of out-of-sample model bias for the realized volatility (RV) of the Dow Jones Industrial Average (DJI) and the S&P 500 (SPX) indices from in-sample and out-of-sample perspectives respectively.FindingsThe in-sample results reveal that the prediction model including the model bias can obtain bigger R2, and the out-of-sample empirical results based on several evaluation methods suggest that the prediction model incorporating model bias can improve forecast accuracy for the RV of the DJI and the SPX indices. That is, model bias can enhance the predictability of original HAR family models.Originality/valueThe author introduce out-of-sample model bias into HAR family models to enhance model capability in predicting realized volatility.

Importance: To date, there is no established evidence of sex-specific differences in altitude-induced sleep-disordered breathing (SDB) during polysomnography-confirmed sleep. Objective: The aim of this study was to investigate whether differences in sex play a pivotal role in incidences of SDB and acute mountain sickness (AMS) when staying overnight at high altitude. Design: This was a prospective cohort study. Setting: Participants underwent overnight polysomnography (PSG) and clinical assessment in a sleep laboratory at 500 m and two consecutive days at 3270 m. Participants: The participants comprised 28 (18 women) healthy, young, low-altitude residents with a median (interquartile range) age of 26.0 (25.0, 28.0) years. Exposures: Altitude exposure. Main outcomes and Measures: The primary outcome was altitude-induced change in the PSG-confirmed apnea–hypopnea index (AHI) at 3270 m compared to 500 m between men and women. Secondary outcomes included sex differences in other parameters related to SDB, sleep structure, AMS, psychomotor vigilance test reaction time and parameters from arterial and venous blood analyses. Results: The median (interquartile range) AHIs at 500 m and 3270 m on night 1 and on night 2 were 6.5/h (3.6, 9.1), 23.7/h (16.2, 42.5) and 15.2/h (11.8, 20.9) in men, respectively, and 2.2/h (1.0, 5.5), 8.0/h (5.3, 17.0) and 7.1/h (4.9, 11.5) in women, respectively (p < 0.05 nights 1 and 2 at 3270 m vs. 500 m in men and women). The median difference (95% CI) of altitude-induced change in AHI (3270 m night 1 compared to 500 m) between men and women was 11.2/h (1.9 to 19.6) (p < 0.05). Over the time course of 2 days at 3270 m, 9 out of 18 (50%) women and 1 out of 10 (10%) men developed AMS (p < 0.05 women versus men). Conclusions and Relevance: This prospective cohort study showed that men were more susceptible to altitude-induced SDB but that they had a lower AMS incidence when staying for 2 days at 3270 m than women. These findings indicate that sex-related prevention and intervention strategies against SDB and AMS are highly warranted. Trial Registration: This trial was registered at the Chinese Clinical Trial Registry; No. ChiCTR1800020155.

Most emerging and re-emerging viruses causing infectious diseases in humans and domestic animals have originated from wildlife. However, current knowledge of the spectrum of RNA viruses in the Qinghai-Tibet Plateau in China is still limited. Here, we performed metatranscriptomic sequencing on fecal samples from 56 birds and 91 small mammals in Tibet and Qinghai Provinces, China, to delineate their viromes and focused on vertebrate RNA viruses. A total of 184 nearly complete genome RNA viruses belonging to 28 families were identified. Among these, 173 new viruses shared Orthonairovirus and Hepatovirus, could be zoonotic viruses. In addition, host taxonomy and geographical location of these viruses showed new hosts and distribution of several previously discovered viruses. Moreover, 12 invertebrate RNA viruses were identified with

[ES] Los usuarios del Examen de Aptitud de Chino (Hanyu Shuiping Kaoshi, denominado HSK) son cada vez más diversos, y ya es hora de que las autoridades competentes investiguen las necesidades de los usuarios del examen y lancen un nuevo examen HSK avanzado. Por lo tanto, este artículo revisa en primer lugar los estudios relevantes de los modelos de análisis de necesidades de lenguas extranjeras, y presenta la importancia de establecer un modelo de análisis de necesidades para el HSK. Basándose en el modelo de análisis de necesidades de Dudley-Evans y St. John y en el modelo de análisis de necesidades de Knoch, U. y Macqueen, S., el artículo propone un marco teórico del modelo de análisis de necesidades del HSK (avanzado) que consta de siete perspectivas: información personal, información lingüística e información profesional, carencias de los estudiantes de chino, satisfacción con el HSK existente, expectativas para el HSK (avanzado), necesidades de recursos para el examen y el impacto de las políticas pertinentes en el examen. También presenta las fuentes de información, los métodos de recogida de información y las posibles preguntas, con el fin de proporcionar una referencia para el desarrollo del HSK (avanzado). [EN] The test users of Chinese Proficiency Test (Hanyu Shuiping Kaoshi, hereinafter referred to as HSK) have been becoming more and more diverse, and it is high time for the concerning authorities to investigate the test users’ needs and launch a new advanced HSK test. Therefore, this paper first reviews the relevant studies of foreign language needs analysis models, and presents the significance to establish a needs analysis model for HSK. Based on Dudley-Evans & St John's needs analysis model and Knoch, U. & Macqueen, S.'s needs analysis model, the paper proposes a theoretical framework of the needs analysis model of HSK (advanced) that consists seven perspectives: personal information, language information and professional information, gap of Chinese language learners, satisfaction with the existing HSK, expectations for HSK (advanced), needs for test resources, and the impact of relevant policies on the test. It also introduces the information sources, information collection methods and possible questions, in order to provide reference for the development of HSK (advanced). [ZH] 近年来，参加汉语水平考试（Hanyu Shuiping Kaoshi，简称HSK）的考生越来越 多样化，有关部门应调查考生需求并推出新的高级HSK考试。本文首先回顾了外语需求分析 模型的相关研究，并提出建立HSK需求分析模型的意义。在Dudley-Evans & St John的需 求分析模型和Knoch, U. & Macqueen, S.的需求分析模型的基础上，本文提出了HSK（高 级）需求分析模型的理论框架，包括七个方面：个人信息、语言信息和专业信息、汉语学 习者的差距、对现有HSK的满意度、对HSK（高级）的期望、对考试资源的需求、相关政策 对考试的影响。报告还介绍了信息来源、信息收集方法和可能出现的问题，为HSK（高级） 的发展提供参考。

This paper studies a class of circuit network model with fractional n-V-structure, the model contains several independent resistance elements, so it is the topology of multiple network models. First, this paper calculates the equivalent resistance of n-V circuit network by constructing equivalent model, and gives two closed equivalent resistance analytic expressions. Additionally, the concept of negative resistance is put forward. A series of special results of equivalent resistance are discussed. Finally, the complex impedance characteristics of fractional n-V structure circuit networks are studied in detail by using variable substitution technique. The amplitude frequency characteristics and phase frequency characteristics of fractional n-V structure circuit network are revealed through Matlab drawing research.

In order to investigate the effect of notoginsenoside Rg1 on cognitive function in 5 ∗ FAD mice and the mechanism of Cx43 in improving cognitive function in mice, the methods 5 ∗ FAD mice are selected as experimental animals and normal mice as healthy control. They were divided into three groups: healthy control group (n = 10), disease group (n = 10), and treatment group (n = 10, Panax notoginsenoside Rg 1150 mg/kg/d) for 2 months. Two months later, three groups of mice were subjected to classical water maze and Y-maze to test the cognitive ability of mice, and the correct response times and total response time were recorded. At the end of the cognitive function test, the mice were executed, and the brain tissues were taken. The expression of Cx43 protein and the changes of glial cells and neurons in the brain of the mice were analyzed at the cellular level. After treatment with Panax notoginseng saponin Rg 1150 mg/kg/d, it was found that the escape latency of mice in the treatment group was significantly lower than that in the disease group from the third day of training ( P < 0.05 ); the time spent on the platform quadrant and the number of times crossing the platform in the treated mice were significantly increased, and the difference was statistically significant ( P < 0.05 ); the expression of Cx43 protein in the brain of mice after treatment was significantly higher than that of mice in the disease group ( P < 0.05 ). Conclusion. Panax notoginseng saponin Rg1 can effectively improve the cognitive function of 5 ∗ FAD mice by increasing the secretion of Cx43 protein, thus increasing the reactivity of glial cells and neurons.

Autophagy is an evolutionarily conserved cellular-degradation mechanism implicated in antiviral defense in plants. Studies have shown that autophagy suppresses virus accumulation in cells, however, it has not been reported to specifically inhibit viral spread in plants. This study demonstrated that infection with citrus leaf blotch virus (CLBV, genus Citrivirus, family Betaflexiviridae) activated autophagy in Nicotiana benthamiana plants as indicated by the increase of autophagosome formation. Impairment of autophagy through silencing of N. benthamiana autophagy-related gene 5 (NbATG5) and NbATG7 enhanced cell-to-cell and systemic movement of CLBV, however, it did not affect CLBV accumulation when the systemic infection had been fully established. Treatment using an autophagy inhibitor or silencing of NbATG5 and NbATG7 revealed that transiently expressed movement protein (MP), but not coat protein, of CLBV was targeted by selective autophagy for degradation. Moreover, we identified that CLBV MP directly interacted with NbATG8C1 and NbATG8i, the isoforms of autophagy-related protein 8 (ATG8), which are key factors that usually bind cargo receptors for selective autophagy. Our results present a novel example in which autophagy specifically targets a viral MP to limit the intercellular spread of the virus in plants.

Although plateau pikas are the keystone species in the plateau ecosystem of the Qinghai Province of China, little is known about their role in the evolution and transmission of viral pathogens, especially coronaviruses. Here, we describe the characterization and evolution of a novel alphacoronavirus, termed plateau pika coronavirus (PPCoV) P83, which has a prevalence of 4.5% in plateau pika fecal samples. In addition to classical gene order, the complete viral genome contains a unique nonstructural protein (NS2), several variable transcription regulatory sequences and a highly divergent spike protein. Phylogenetic analysis indicates that the newly discovered PPCoV falls into the genus Alphacoronavirus and is most closely related to rodent alphacoronaviruses. The co-speciation analysis shows that the phylogenetic trees of the alphacoronaviruses and their hosts are not always matched, suggesting inter-species transmission is common in alphacoronaviruses. And, PPCoV origin was estimated by molecular clock based on membrane and RNA-dependent RNA polymerase encoding genes, respectively, which revealed an apparent discrepancy with that of co-speciation analysis. PPCoV was detected mainly in intestinal samples, indicating a potential enteric tropism for the virus. Overall, this study extends the host range of alphacoronaviruses to a new order (Lagomorpha), indicating that plateau pikas may be the natural reservoir of PPCoV and play an important and long-term role in alphacoronavirus evolution.

Traditional methods of cyanides' (CN

BACKGROUND Galangin is believed to exert antioxidant effects by inhibition of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, which has been linked to chemotherapy sensitivity in cancers. In this study, we explored the synergistic effect of galangin in combination with the chemotherapy agent 5-fluorouracil (5-FU) in esophageal cancer cells and xenografts. MATERIAL AND METHODS The esophageal squamous epithelium cell line Het-1A and 2 human esophageal cancer cell lines (Eca109, OE19) were used to investigate the effect of galangin with or without 5-FU in vitro through proliferation and invasion analyses, while apoptosis was analyzed in cancer cells. Furthermore, a subcutaneous xenograft tumor model in mice was used to study cancer development in vivo. RESULTS Compared with 5-FU monotherapy, combined galangin and 5-FU treatment reduced human esophageal cancer cell growth activities and invasion abilities. The results suggested that galangin had a chemotherapy-sensitized synergistic antitumor effect induced by 5-FU. The susceptibility of cancer cells to apoptosis, which is linked with chemotherapy sensitivity, was induced by 5-FU and further enhanced by galangin. NLRP3 was identified as being significantly activated by 5-FU, but galangin treatment reversed the effect and inhibited NLRP3 expression, which was accompanied by downregulated interleukin-1b levels. Further investigation showed that the induced apoptotic cascade can be mostly reversed by incubation with an NLRP3 activator, irrespective of AKT signaling. Using xenograft mouse models, we found that galangin exposure further restrained cancer development after 5-FU treatment and increased sensitivity to chemotherapy by suppressing the NLRP3 inflammasome pathway. CONCLUSIONS Our results indicated that galangin played a synergistic anticancer role through NLRP3 inflammasome inhibition when paired with FU-5.

Diagnosis of neurosyphilis is currently based on the cerebrospinal fluid (CSF) assessments and CSF-Venereal Disease Research Laboratory (CSF-VDRL) is the traditional "gold standard." In the real world, CSF assessments and CSF-VDRL are not always available. This study aimed to identify noninvasive predictors of neurosyphilis based on real-world clinical parameters and diagnostic criteria in populations with different HIV status. In this retrospective cohort study, syphilis patients with different HIV statuses hospitalized for neurosyphilis screening were retrospectively recruited at an infectious disease hospital. Neurosyphilis was defined by real-world diagnostic criteria. Logistic regression and receiver operating characteristic curve analysis were used to investigate and evaluate predictors of neurosyphilis. In total, 528 patients were enrolled, including 143 syphilis patients without HIV infection and 385 HIV/syphilis-co-infected patients. One hundred twelve and 304 neurosyphilis patients were identified in the HIV-negative and HIV-positive groups, respectively. A high serum toluidine red unheated serum test (TRUST) titer was a robust predictor of neurosyphilis in all participants. An age ≥50 years old [adjusted odds ratio (aOR) = 5.062, 95% confidence interval (CI), 1.449-17.680] in the HIV-negative group and CD4

Singlet oxygen (