Establishment of an induced pluripotent stem cell (SIAISi016-A) line from a 62-years old Chinese Han patient with Alzheimer's disease.

A 62-years old Alzheimer's disease (AD) male patient donated his Peripheral blood mononuclear cells. The non-integrating episomal vector system used to reprogram PBMCs with Oct3/4, Klf4, Sox2 and c-Myc transcription factors. The pluripotency of transgene-free pluripotent stem cell (iPSC) was confirmed by immunocytochemistry for pluripotency markers-SOX2, NANOG, OCT3/4, SSEA4, TRA1-60, and TRA1-81. The differentiation capacity of the iPSCs into endoderm, mesoderm and ectoderm was assessed by AFP, SMA and ßIII-TUBULIN, respectively. In addition, the iPSC line displayed a normal karyotype. This iPSC line might offer a good cell model to explore the pathological mechanisms and treatment strategies for AD.

Rapid identification of adulteration in raw bovine milk with soymilk by electronic nose and headspace-gas chromatography ion-mobility spectrometry.

The adulteration of soymilk (SM) into raw bovine milk (RM) to gain profit without declaration could cause a health risk. In this study, electronic nose (E-nose) and headspace-gas chromatography ion-mobility spectrometry (HS-GC-IMS) were applied to establish a rapid and effective method to identify adulteration in RM with SM. The obtained data from HS-GC-IMS and E-nose can distinguish the adulterated samples with SM by principal component analysis. Furthermore, a quantitative model of partial least squares was established. The detection limits of E-nose and HS-GC-IMS quantitative models were 1.53% and 1.43%, the root mean square errors of prediction were 0.7390 and 0.5621, the determination coefficients of prediction were 0.9940 and 0.9958, and the relative percentage difference were 10.02 and 13.27, respectively, indicating quantitative regression and good prediction performances of SM adulteration levels in RM were achieved. This research can provide scientific information on the rapid, non-destructive and effective adulteration detection for RM.

Feasibility of accelerated non-contrast-enhanced whole-heart bSSFP coronary MR angiography by deep learning-constrained compressed sensing.

OBJECTIVES: To examine a compressed sensing artificial intelligence (CSAI) framework to accelerate image acquisition in non-contrast-enhanced whole-heart bSSFP coronary magnetic resonance (MR) angiography. METHODS: Thirty healthy volunteers and 20 patients with suspected coronary artery disease (CAD) scheduled for coronary computed tomography angiography (CCTA) were enrolled. Non-contrast-enhanced coronary MR angiography was performed with CSAI, compressed sensing (CS), and sensitivity encoding (SENSE) methods in healthy participants and with CSAI in patients. Acquisition time, subjective image quality score, and objective image quality measurement (blood pool homogeneity, signal-to-noise ratio [SNR], and contrast-to-noise ratio [CNR]) were compared among the three protocols. The diagnostic performance of CASI coronary MR angiography for predicting significant stenosis (≥ 50% diameter stenosis) on CCTA was evaluated. The Friedman test was performed to compare the three protocols. RESULTS: Acquisition time was significantly shorter in the CSAI and CS groups than in the SENSE group (10.2 ± 3.2 min vs. 10.9 ± 2.9 min vs. 13.0 ± 4.1 min, p < 0.001). However, the CSAI approach had the highest image quality scores, blood pool homogeneity, mean SNR value, and mean CNR value (all p < 0.001) compared with the CS and SENSE approaches. The sensitivity, specificity, and accuracy of CSAI coronary MR angiography per patient were 87.5% (7/8), 91.7% (11/12), and 90.0% (18/20); those per vessel were 81.8% (9/11), 93.9% (46/49), and 91.7% (55/60); and those per segment were 84.6% (11/13), 98.0% (244/249), and 97.3% (255/262), respectively. CONCLUSIONS: CSAI yielded superior image quality within a clinically feasible acquisition time in healthy participants and patients with suspected CAD. CLINICAL RELEVANCE STATEMENT: The non-invasive and radiation-free CSAI framework could be a promising tool for rapid screening and comprehensive examination of the coronary vasculature in patients with suspected CAD. KEY POINTS: • This prospective study showed that CSAI enables a reduction in acquisition time by 22% with superior diagnostic image quality compared with the SENSE protocol. • CSAI replaces the wavelet transform with a CNN as a sparsifying transform in the CS algorithm, achieving high coronary MR image quality with reduced noise. • CSAI achieved per-patient sensitivity of 87.5% (7/8) and specificity of 91.7% (11/12) respectively for detecting significant coronary stenosis.

Colorimetric and visual sensing of ferrous ion by Fenton reaction-stimulated etching of triangular gold nanoplates.

In this study, a method for ultrasensitive sensing of Fe2+ based on Fenton reaction mediated etching of triangular gold nanoplates (Au NPLs) was developed. In this assay, the etching of Au NPLs by H2O2 was accelerated in the presence of Fe2+ due to the generation of superoxide free radical (O2·-) via Fenton reaction. With the concentration of Fe2+ increased, the shape of Au NPLs changed from triangular to sphere with the blue shifted localized surface plasmon resonance, accompanying a series of consecutive color changes from blue, bluish purple, purple, reddish purple and finally to pink. The rich color variations enable rapid visual quantitative determination of Fe2+ within 10 min. A good linear relationship between the peak shifts and the concentration of Fe2+ was obtained in the range of 0.035 to 1.5 µM (R2 = 0.996). Favorable sensitivity and selectivity in the presence of other tested metal ions were achieved in the proposed colorimetric assay. The detection limits (3Æ¡/k) for Fe2+ was 26 nM by UV-vis spectroscopy, and the clearly discernible concentration of Fe2+ was as low as 0.07 µM by naked eyes. The recoveries of fortified samples in pond water and serum samples ranged from 96% to 106% with interday relative standard deviations <3.6% in all cases, demonstrating the applicability of the assay for measuring Fe2+ in real samples.

Roles of long non-coding RNAs in plant immunity.

Robust plant immune systems are fine-tuned by both protein-coding genes and non-coding RNAs. Long non-coding RNAs (lncRNAs) refer to RNAs with a length of more than 200 nt and usually do not have protein-coding function and do not belong to any other well-known non-coding RNA types. The non-protein-coding, low expression, and non-conservative characteristics of lncRNAs restrict their recognition. Although studies of lncRNAs in plants are in the early stage, emerging studies have shown that plants employ lncRNAs to regulate plant immunity. Moreover, in response to stresses, numerous lncRNAs are differentially expressed, which manifests the actions of low-expressed lncRNAs and makes plant-microbe/insect interactions a convenient system to study the functions of lncRNAs. Here, we summarize the current advances in plant lncRNAs, discuss their regulatory effects in different stages of plant immunity, and highlight their roles in diverse plant-microbe/insect interactions. These insights will not only strengthen our understanding of the roles and actions of lncRNAs in plant-microbe/insect interactions but also provide novel insight into plant immune responses and a basis for further research in this field.

Agomelatine in the treatment of anhedonia, somatic symptoms, and sexual dysfunction in major depressive disorder.

Objective: This study evaluated the treatment outcomes of agomelatine on anhedonic state, anxiety/somatic symptoms, and sexual function in Chinese patients with major depressive disorder (MDD). Method: In total, 93 adult patients with MDD were enrolled, and 68 of them were included in a prospective, open-label, multicenter clinical study. All patients received agomelatine monotherapy during a 9-week treatment phase. The effectiveness of the treatment was reflected by the improvement of anhedonia and somatic symptoms based on the 17-item Hamilton Depression Rating Scale (HAMD-17). In addition, the Arizona Sexual Dysfunction Scale (ASEX), Sheehan Disability Scale (SDS), and Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) were administered to all participants at baseline and at the 3-, 6-, and 9-week follow-ups. Results: After 9 weeks of treatment with agomelatine, the response and remission rates were 73.5% and 39.7%, respectively. Somatic symptoms significantly improved at week 9 (p < 0.001), and significant effects were also observed on the HAMD anhedonia items (p < 0.001). The patients exhibited lower levels of disease severity (the SDS score dropped from 15.52 ± 4.7 to 7.09 ± 5.62 at week 9; the ASEX score dropped from 21.89 ± 4.06 to 16.19 ± 4.79, p < 0.001) and higher levels of QOL (the Q-LES-Q-SF score dropped from 41.02 ± 5.99 to 50.49 ± 8.57, p < 0.001) during the follow-up. Furthermore, treatment with agomelatine improved depressive symptoms without causing serious adverse events. Conclusion: These analyses indicate that agomelatine is a treatment option for improving anhedonic status, anxiety/somatic symptoms, and sexual dysfunction in MDD patients.

Characterisation of the Aroma Profile and Dynamic Changes in the Flavour of Stinky Tofu during Storage.

Stinky tofu is a traditional Chinese food with wide consumption in China. Nevertheless, the dynamic changes in the flavour of stinky tofu during storage have yet to be investigated. In this study, the flavour changes of stinky tofu over six different storage periods were comprehensively analysed through sensory, electronic nose and gas chromatography-mass spectrometry (GC-MS) analyses. The results of the sensory and electronic nose analyses confirmed the changes in the flavour of stinky tofu across different storage periods. In the GC-MS analysis, 60 volatile compounds were detected during storage, and the odour activity values indicated that 29 of these 60 compounds significantly contributed to the aroma profile. During storage, the alcohol concentration of the stinky tofu gradually decreased while the acid and ester concentrations increased. According to a partial least squares analysis, 2-phenylethyl acetate, 2-phenylethyl propanoate, p-cresol, and phenylethyl alcohol, which were detected after 10 days of storage, promoting the release of an overripe apple-like odour from the stinky tofu. Findings regarding the flavour changes and characteristics of stinky tofu during different storage periods can provide a potential reference for recognising the quality of these products.

Natural bioactive compounds in Alzheimer's disease: From the perspective of type 3 diabetes mellitus.

There is a close relationship between Alzheimer's disease (AD) and diabetes mellitus (DM), and the link between the two is often referred to as type 3 diabetes mellitus (T3DM). Many natural bioactive compounds have shown the potential to treat AD and diabetes. We mainly review the polyphenols represented by resveratrol (RES) and proanthocyanidins (PCs) and alkaloids represented by berberine (BBR) and Dendrobium nobile Lindl. alkaloids (DNLA) from the perspective of T3DM to review the neuroprotective effects and molecular mechanisms of natural compounds in AD.

Bacterial DNA methyltransferase: A key to the epigenetic world with lessons learned from proteobacteria.

Epigenetics modulates expression levels of various important genes in both prokaryotes and eukaryotes. These epigenetic traits are heritable without any change in genetic DNA sequences. DNA methylation is a universal mechanism of epigenetic regulation in all kingdoms of life. In bacteria, DNA methylation is the main form of epigenetic regulation and plays important roles in affecting clinically relevant phenotypes, such as virulence, host colonization, sporulation, biofilm formation et al. In this review, we survey bacterial epigenomic studies and focus on the recent developments in the structure, function, and mechanism of several highly conserved bacterial DNA methylases. These methyltransferases are relatively common in bacteria and participate in the regulation of gene expression and chromosomal DNA replication and repair control. Recent advances in sequencing techniques capable of detecting methylation signals have enabled the characterization of genome-wide epigenetic regulation. With their involvement in critical cellular processes, these highly conserved DNA methyltransferases may emerge as promising targets for developing novel epigenetic inhibitors for biomedical applications.

RNF123 Mediates Ubiquitination and Degradation of SOCS1 To Regulate Type I Interferon Production during Duck Tembusu Virus Infection.

Many RING domain E3 ubiquitin ligases play critical roles in fine-tuning the innate immune response, yet little is known about their regulatory role in flavivirus-induced innate immunity. In previous studies, we found that the suppressor of cytokine signaling 1 (SOCS1) protein mainly undergoes lysine 48 (K48)-linked ubiquitination. However, the E3 ubiquitin ligase that promotes the K48-linked ubiquitination of SOCS1 is unknown. In the present study, we found that RING finger protein 123 (RNF123) binds to the SH2 domain of SOCS1 through its RING domain and facilitates the K48-linked ubiquitination of the K114 and K137 residues of SOCS1. Further studies found that RNF123 promoted the proteasomal degradation of SOCS1 and promoted Toll-like receptor 3 (TLR3)- and interferon (IFN) regulatory factor 7 (IRF7)-mediated type I IFN production during duck Tembusu virus (DTMUV) infection through SOCS1, ultimately inhibiting DTMUV replication. Overall, these findings demonstrate a novel mechanism by which RNF123 regulates type I IFN signaling during DTMUV infection by targeting SOCS1 degradation. IMPORTANCE In recent years, posttranslational modification (PTM) has gradually become a research hot spot in the field of innate immunity regulation, and ubiquitination is one of the critical PTMs. DTMUV has seriously endangered the development of the waterfowl industry in Southeast Asian countries since its outbreak in 2009. Previous studies have shown that SOCS1 is modified by K48-linked ubiquitination during DTMUV infection, but E3 ubiquitin ligase catalyzing the ubiquitination of SOCS1 has not been reported. Here, we identify for the first time that RNF123 acts as an E3 ubiquitin ligase that regulates TLR3- and IRF7-induced type I IFN signaling during DTMUV infection by targeting the K48-linked ubiquitination of the K114 and K137 residues of SOCS1 and the proteasomal degradation of SOCS1.

Real-world efficacy and safety of pyrotinib in patients with HER2-positive metastatic breast cancer: A prospective real-world study.

Background: Pyrotinib, a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor, shows encouraging anticancer activity and acceptable tolerability in multiple phase II and phase III randomized clinical trials, but the real-world data of pyrotinib, especially the outcomes in HER2-positive metastatic breast cancer, have been rarely reported. Here, we evaluated the treatment outcomes of pyrotinib in real-world practice in patients with HER2-positive metastatic breast cancer (MBC). Methods: This was a prospective, real-world, observational cohort study. Through the Breast Cancer Information Management System, HER-2 positive MBC patients treated with pyrotinib between 2017/06 and 2020/09 were included. Provider-reported objective response rate, progression-free survival (PFS), and overall survival (OS) were considered in the assessment of treatment outcomes. Tumor responses to pyrotinib treatment were calculated using RECIST 1.1. Adverse events were evaluated using clinical records. Results: The trial involved 113 individuals who were receiving pyrotinib treatment, with an average age of 51 years. Complete response, partial response and stable disease were observed in 9 (8.0%), 66 (58.4%), and 17 (15.0%) patients, respectively, while progressive disease was recorded in 20 (17.7%) patients. After a median follow-up of 17.2 months, the median PFS was 14.1. The most common adverse events of any grade were diarrhea (87.6%), vomiting (31.9%), and palmar-plantar erythrodysesthesia (26.6%). Among the patients with brain metastases, the median PFS and OS were 15.2 and 19.8 months, respectively. In addition, pyrotinib has similar efficacy in various subtypes of HER2-positive MBC patients, as shown by the lack of a significant difference of PFS and OS among pyrotinib-treated patients with or without brain metastases, or patients using pyrotinib as first-line, second-line, third-line or beyond therapies. Conclusion: Our real-world results demonstrated equivalent clinical efficacy in HER-2 positive MBC patients compared to phase II and phase III clinical trials with pyrotinib, and promising outcomes in patients with brain metastases.

Effect of multidisciplinary health education based on lifestyle medicine on menopausal syndrome and lifestyle behaviors of menopausal women: A clinical controlled study.

Background: Menopausal women may experience menopausal syndrome and long-term effects caused by low estrogen levels, such as senile dementia and osteoporosis in the elderly. Most menopausal women may have misconceptions about menopause and low use of pharmacological interventions. These misconceptions may damage the quality of life and miss the critical period for preventing senile diseases. Thus, enhancing the awareness of menopausal women regarding psychosocial and physical changes through health education programs was a way to improve positive attitudes toward menopause and make further treatment options. Objectives: This study aimed to evaluate the effect of multidisciplinary health education based on lifestyle medicine on menopausal syndrome and lifestyle behaviors of menopausal women. Methods: The study was conducted in several hospitals in Chongqing, China. The two groups were from different hospitals with similar medical levels in order to reduce information contamination. It was designed as a clinical controlled trial in which the intervention group (n = 100) and control group (n = 87) were matched for age, age at menarche, menopausal symptoms and drug use status at enrollment. Women in the intervention group received multidisciplinary health education based on lifestyle medicine for 2 months while those in the control group received routine outpatient health guidance. Menopausal syndrome, physical activity and dietary status of participants were assessed before and after the intervention. Paired t-tests and Independent-sample t-tests were adopted for comparison within and between groups, respectively, in the normal variables. Wilcoxon signed-rank tests and Mann-Whitney U tests were adopted for comparison within and between group, respectively, in the abnormal variables. Categorical variables were tested using Pearson's χ2. P-value < 0.05 was statistically significant in statistical tests. Results: Post intervention testing indicated that menopausal syndrome of participants was significantly improved in the intervention group compared to the control group (P < 0.001). Between-group comparison showed a significant improvement of weekly energy expenditure of total physical activity (P = 0.001) and participation in exercise (P < 0.001) in the intervention group compared to the control group after the intervention. The dietary status of participants was significantly improved in the intervention group compared to the control group (P < 0.001). In the intervention group, the menopausal syndrome of participants improved more in the hormone drug group than in the non-hormone group (P = 0.007), as did the control group (P = 0.02). In the hormone drug group, the physical activity (P = 0.003) and dietary status (P = 0.001) mproved more in the intervention group than in the control group. Conclusions: The multidisciplinary health education based on lifestyle medicine was effective in improving the menopausal syndrome and healthy lifestyle behaviors of menopausal women. Studies with extended observation period and larger sample size are in need to evaluate the long-term scale-up effects of the multidisciplinary health education.

Emerging trends and focus on the link between gut microbiota and type 1 diabetes: A bibliometric and visualization analysis.

Objective: To conduct the first thorough bibliometric analysis to evaluate and quantify global research regarding to the gut microbiota and type 1 diabetes (T1D). Methods: A literature search for research studies on gut microbiota and T1D was conducted using the Web of Science Core Collection (WoSCC) database on 24 September 2022. VOSviewer software and the packages Bibliometrix R and ggplot used in RStudio were applied to perform the bibliometric and visualization analysis. Results: A total of 639 publications was extracted using the terms "gut microbiota" and "type 1 diabetes" (and their synonyms in MeSH). Ultimately, 324 articles were included in the bibliometric analysis. The United States and European countries are the main contributors to this field, and the top 10 most influential institutions are all based in the United States, Finland and Denmark. The three most influential researchers in this field are Li Wen, Jorma Ilonen and Mikael Knip. Historical direct citation analysis showed the evolution of the most cited papers in the field of T1D and gut microbiota. Clustering analysis defined seven clusters, covering the current main topics in both basic and clinical research on T1D and gut microbiota. The most commonly found high-frequency keywords in the period from 2018 to 2021 were "metagenomics," "neutrophils" and "machine learning." Conclusion: The application of multi-omics and machine learning approaches will be a necessary future step for better understanding gut microbiota in T1D. Finally, the future outlook for customized therapy toward reshaping gut microbiota of T1D patients remains promising.

NLRP6 deficiency expands a novel CD103+ B cell population that confers immune tolerance in NOD mice.

Introduction: Gut microbiota have been linked to modulating susceptibility to Type 1 diabetes; however, there are many ways in which the microbiota interact with host cells, including through microbial ligand binding to intracellular inflammasomes (large multi-subunit proteins) to initiate immune responses. NLRP6, a microbe-recognizing inflammasome protein, is highly expressed by intestinal epithelial cells and can alter susceptibility to cancer, obesity and Crohn's disease; however, the role of NLRP6 in modulating susceptibility to autoimmune diabetes, was previously unknown. Methods: We generated NLRP6-deficient Non-obese diabetic (NOD) mice to study the effect of NLRP6-deficiency on the immune cells and susceptibility to Type 1 diabetes development. Results: NLRP6-deficient mice exhibited an expansion of CD103+ B cells and were protected from type 1 diabetes. Moreover, NLRP6-deficient CD103+ B cells express regulatory markers, secreted higher concentrations of IL-10 and TGFb1 cytokines and suppressed diabetogenic T cell proliferation, compared to NLRP6-sufficient CD103+ B cells. Microarray analysis of NLRP6-sufficient and -deficient CD103+ B cells identified 79 significantly different genes including genes regulated by lipopolysaccharide (LPS), tretinoin, IL-10 and TGFb, which was confirmed in vitro following LPS stimulation. Furthermore, microbiota from NLRP6-deficient mice induced CD103+ B cells in colonized NLRP6-sufficient germ-free mice; however, the long-term maintenance of the CD103+ B cells required the absence of NLRP6 in the hosts, or continued exposure to microbiota from NLRP6-deficient mice. Discussion: Together, our data indicate that NLRP6 deficiency promotes expansion and maintenance of a novel TGF -dependent CD103+ Breg population. Thus, targeting NLRP6 therapeutically may prove clinically useful.

Selenium deficiency causes hypertension by increasing renal AT1 receptor expression via GPx1/H2O2/NF-κB pathway.

Epidemiological studies show an association between low body selenium and the risk of hypertension. However, whether selenium deficiency causes hypertension remains unknown. Here, we report that Sprague-Dawley rats fed a selenium-deficient diet for 16 weeks developed hypertension, accompanied with decreased sodium excretion. The hypertension of selenium-deficient rats was associated with increased renal angiotensin II type 1 receptor (AT1R) expression and function that was reflected by the increase in sodium excretion after the intrarenal infusion of the AT1R antagonist candesartan. Selenium-deficient rats had increased systemic and renal oxidative stress; treatment with the antioxidant tempol for 4 weeks decreased the elevated blood pressure, increased sodium excretion, and normalized renal AT1R expression. Among the altered selenoproteins in selenium-deficient rats, the decrease in renal glutathione peroxidase 1 (GPx1) expression was most prominent. GPx1, via regulation of NF-κB p65 expression and activity, was involved in the regulation of renal AT1R expression because treatment with dithiocarbamate (PDTC), an NF-κB inhibitor, reversed the up-regulation of AT1R expression in selenium-deficient renal proximal tubule (RPT) cells. The up-regulation of AT1R expression with GPx1 silencing was restored by PDTC. Moreover, treatment with ebselen, a GPX1 mimic, reduced the increased renal AT1R expression, Na+-K+-ATPase activity, hydrogen peroxide (H2O2) generation, and the nuclear translocation of NF-κB p65 protein in selenium-deficient RPT cells. Our results demonstrated that long-term selenium deficiency causes hypertension, which is due, at least in part, to decreased urine sodium excretion. Selenium deficiency increases H2O2 production by reducing GPx1 expression, which enhances NF-κB activity, increases renal AT1R expression, causes sodium retention and consequently increases blood pressure.

Breast milk jaundice affects breastfeeding: From the perspective of intestinal flora and SCFAs-GPR41/43.

Breast milk jaundice (BMJ) is one of the main factors leading to interruption or early termination of breastfeeding. Interrupting breastfeeding to treat BMJ may increase the adverse consequences for infant growth and disease prevention. The Intestinal flora and metabolites are increasingly recognized as a potential therapeutic target in BMJ. First, dysbacteriosis can lead to a decrease in the metabolite short-chain fatty acids. At the same time, SCFA can act on specific G protein-coupled receptors 41 and 43 (GPR41/43), and a decrease in SCFA downregulates the GPR41/43 pathway, leading to a diminished inhibition of intestinal inflammation. In addition, intestinal inflammation leads to a decrease in intestinal motility and a large amount of bilirubin enters the enterohepatic circulation. Ultimately, these changes will result in the development of BMJ. In this review, we will describe the underlying pathogenetic mechanism of the intestinal flora effects on BMJ.

Elevated HMGB1 and sRAGE levels in cerebrospinal fluid of aneurysmal subarachnoid hemorrhage patients.

BACKGROUND: Neuroinflammation after aneurysmal subarachnoid hemorrhage (aSAH) leads to poor outcome of patients. High mobility group box 1 (HMGB1) contributes to inflammation through binding to receptors for advanced glycation end-products (RAGE) in various diseases. We aimed to determine the production of these two factors after aSAH and their relationship with clinical features. METHODS: HMGB1 and soluble RAGE (sRAGE) levels in cerebrospinal fluid (CSF) of aSAH patients and controls were measured, and their temporal courses were observed. The correlation between early concentrations (days 1-3) and clinical symptoms assessed by disease severity scores, neuroinflammation estimated by CSF IL-6 levels, as well as prognosis evidenced by delayed cerebral ischemia (DCI) and 6-month adverse outcome was investigated. Finally, combined analysis of early levels for predicting prognosis was confirmed. RESULTS: CSF HMGB1 and sRAGE levels were higher in aSAH patients than in controls (P < 0.05), and the levels decreased from higher early to lower over time. Their early concentrations were positively associated with disease severity scores, IL-6 levels, DCI and 6-month poor outcome (P < 0.05). HMGB1 ≥ 6045.5 pg/ml (OR = 14.291, P = 0.046) and sRAGE ≥ 572.0 pg/ml (OR = 13.988, P = 0.043) emerged as independent predictors for DCI, while HMGB1 ≥ 5163.2 pg/ml (OR = 7.483, P = 0.043) and sRAGE ≥ 537.3 pg/ml (OR = 12.653, P = 0.042) were predictors for 6-month poor outcome. Combined analysis of them improved predictive values of adverse prognosis. CONCLUSION: CSF HMGB1 and sRAGE levels of aSAH patients were increased early and then varied dynamically, which might act as potential biomarkers for poor outcome, especially when co-analyzed.

Deleting UL49.5 in duck plague virus causes attachment, entry and spread defects.

Duck plague is a disease with high morbidity and mortality rates, and it causes great losses for the duck breeding industry. Duck plague virus (DPV) is the causative agent of duck plague, and DPV UL49.5 protein (pUL49.5) is homologue of glycoprotein N (gN), which is conserved in herpesviruses. UL49.5 homologues are known to be involved in processes such as immune escape, virus assembly, viral fusion, transporter associated with antigen processing (TAP) inhibition and degradation, and maturation and incorporation of glycoprotein M. However, few studies have focused on the role of gN in the early stage of virus infection cells. In this study, we determined that DPV pUL49.5 was distributed in the cytoplasm and colocalized with the endoplasmic reticulum (ER). Moreover, we found that DPV pUL49.5 was a virion component and nonglycosylated protein. To better explore its function, BAC-DPV-ΔUL49.5 was constructed, and its attachment was only approximately 25 % of the revertant virus. Additionally, the penetration ability of BAC-DPV-ΔUL49.5 has only reached 73 % of the revertant virus. The plaque sizes produced by the UL49.5-deleted virus were approximately 58 % smaller than those produced by the revertant virus. Deleting UL49.5 mainly resulted in attachment and cell-to-cell-spread defects. Taken together, these findings suggest important roles for DPV pUL49.5 in viral attachment, penetration and spread.

Environmental Effects of China's Export Trade to the Countries along Belt and Road: An Empirical Evidence Based on Inter-Provincial Panel Data.

There is a close inherent connection between manufacturing exports and environmental pollution. With the continuous growth of China's export trade to the countries along Belt and Road, the resulting environmental problems have also received much attention. This paper first analyzes the environmental impact mechanism of China's export trade to the countries along Belt and Road. Then based on the dynamic panel data of 30 provinces in China from 2013 to 2019, we use the SYS-GMM method to make an empirical test from national and regional perspectives and analyze the environmental effects of China's export trade to the countries along Belt and Road. The results show that the environmental effects of export trade are significantly heterogeneous in different regions. In general, export trade has a significant positive scale effect on CO2 emissions; the negative effect of environmental regulation on CO2 emissions can effectively offset the positive effect caused by the growth of output in the capital-intensive sector, and the composition effect is generally negative; the technical effect of China's export trade to the countries along Belt and Road mainly depends on the technological-independent innovation, which is caused by the domestic investment in science and technology, so the overall technical effects are negative. Therefore, China should optimize the structure of export trade, promote technological innovation, and cultivate green advantage industries by increasing investment in scientific research and development; implement a gradient environmental regulation policy; and improve the quality and level of foreign direct investment.

Establishment and application of a PCR assay for the identification of virulent and attenuated duck plague virus DNA in cotton swabs.

Duck plague is an acute, febrile, and septic infectious disease caused by duck plague virus (DPV), which causes serious harm to the duck industry in China. Ducks latently infected with DPV display a clinically healthy state, which is one of the epidemiological characteristics of duck plague. In the present study, to rapidly distinguish vaccine-immunized ducks from wild virus-infected ducks during production, a PCR assay based on the newly identified LORF5 fragment was developed to effectively and accurately identify viral DNA in cotton swab samples and was used to assess artificial infection models and clinical samples. The results showed that the established PCR method had good specificity and that only the virulent and attenuated DNA of duck plague virus was specifically amplified, as the results for the detection of common duck pathogens (duck hepatitis B virus, duck Tembusu virus, duck hepatitis A virus type 1, novel duck reovirus, Riemerella anatipestifer, Pasteurella multocida, and Salmonella) were negative. The amplified fragments of virulent and attenuated strains were 2,454 bp and 525 bp, and their minimum detection amounts were 0.46 pg and 46 pg, respectively. The detection rate of the virulent and attenuated DPV strains in duck oral and cloacal swabs was lower than that of the gold standard PCR method (GB-PCR, which is unable to distinguish virulent and attenuated strains), and cloacal swabs from clinically healthy ducks were more suitable for detection than oral swabs. In conclusion, the PCR assay established in the present study can be used as a simple and effective method for the clinical screening of ducks that are latently infected with virulent strains of DPV and shedding virus, which can provide technical support for the elimination of duck plague from duck farms.