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Zhi-Xin Huang,1,2,* Li-Hua Chen,3,* Ran Xiong,4 Yan-Ni He,4 Zhu Zhang,1,2 Jie Zeng,5 Qiankun Cai,6 Zhenguo Liu7 1Department of Neurology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, People’s Republic of China; 2Department of Neurology, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Neurology, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Ultrasonography, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, People’s Republic of China; 5Department of Center for Clinical Epidemiology and Methodology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, People’s Republic of China; 6Department of Neurology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, People’s Republic of China; 7Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USA*These authors contributed equally to this work.Correspondence: Zhi-Xin HuangDepartment of Neurology, Guangdong Second Provincial General Hospital, 466 Middle Xingang Road, Guangzhou 510317, Guangdong, People’s Republic of ChinaTel/Fax +86 20 89168080Email hzxd6@163.comZhenguo LiuCenter for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USAEmail liuzheng@health.missouri.eduBackground: Carotid atherosclerosis (CA) is closely related to stroke, and Framingham Risk Score (FRS) has been used for CA risk evaluation. However, FRS could only be used for subjects of up to 74 years old. The present study was to determine if Essen Stroke Risk Score (ESRS) could be used to estimate CA risk in community populations without age limits.Methods: In the present prospective multi-community screening study, we evaluated the prevalence of CA using high-resolution ultrasound in 521 males and 1039 females (35 to 91 years old). Both FRS and ESRS were calculated for the subjects. Multivariate logistic regression analysis was used to determine the predictive values of FRS and ESRS for CA in these subjects.Results: Ultrasound data showed that CA was present in 56.2% of the participants (total of 1560). Multivariate logistic regression analysis showed that ESRS was associated with CA with odds ratio (OR): 1.34 (95% confidence interval (CI), 1.12– 1.60, p=0.001). Central obesity (OR: 1.40, CI: 1.07– 1.83, p=0.015), female (OR: 0.55, CI: 0.39– 0.77, p < 0.001) and age (OR: 2.63, CI: 2.27– 3.06, p < 0.001) were also associated with CA. Based on the estimated area under curve (AUC), FRS (AUC 0.775) was better than ESRS (AUC 0.693) (z statistic 6.774, p < 0.001) for CA prediction for individuals of ≤ 74 years old. However, receiver operating characteristic analysis showed ESRS was a good CA predictor for all subjects (AUC of 0.715).Conclusion: ESRS could be used as an alternative to FRS to predict CA in community population of all age.Keywords: Essen Stroke Risk Score, ESRS, carotid atherosclerosis, risk factors, stroke

Fu Jin,1 Huan-Li Luo,1 Juan Zhou,2 Ya-Nan He,1 Xian-Feng Liu,1 Ming-Song Zhong,1 Han Yang,1 Chao Li,1 Qi-Cheng Li,1 Xia Huang,1 Xiu-Mei Tian,1 Da Qiu,1 Guang-Lei He,1 Li Yin,1 Ying Wang1 1Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing Cancer Institute, Chongqing Cancer Hospital, Chongqing, People’s Republic of China; 2Forensic Identification Center, College of Criminal Investigation, Southwest University of Political Science and Law, Chongqing, People’s Republic of China Abstract: Modern radiotherapy (RT) is being enriched by big digital data and intensive technology. Multimodality image registration, intelligence-guided planning, real-time tracking, image-guided RT (IGRT), and automatic follow-up surveys are the products of the digital era. Enormous digital data are created in the process of treatment, including benefits and risks. Generally, decision making in RT tries to balance these two aspects, which is based on the archival and retrieving of data from various platforms. However, modern risk-based analysis shows that many errors that occur in radiation oncology are due to failures in workflow. These errors can lead to imbalance between benefits and risks. In addition, the exact mechanism and dose–response relationship for radiation-induced malignancy are not well understood. The cancer risk in modern RT workflow continues to be a problem. Therefore, in this review, we develop risk assessments based on our current knowledge of IGRT and provide strategies for cancer risk reduction. Artificial intelligence (AI) such as machine learning is also discussed because big data are transforming RT via AI. Keywords: cancer risk, radiotherapy, workflow, big data

Introduction: Hypertension, a prevalent cardiovascular disease globally, poses significant health risks and economic burden. Evolving treatment targets necessitate more intensive strategies, such as low-dose triple or quadruple drug combinations. However, a systematic comparison of different low-dose antihypertensive combinations is still lacking. The aim of the present study is to systematically and comprehensively evaluate the blood pressure-lowering effect and the associated safety of diverse low-dose polypharmacy combinations in patients with hypertension., Methods and Analysis: In this systematic review and network meta-analysis, randomised controlled trials comparing diverse low-dose polypharmacy combinations with placebo or active treatments in patients with hypertension will be eligible for inclusion. The primary outcomes are a reduction in systolic/diastolic blood pressure, the rate of target blood pressure, adverse effects, serious adverse effects and all-cause dropout after treatment. PubMed, Web of Science, Embase, Cochrane Library, Chinese Science Citation Database, Wanfang Medical Network, VIP Database and clinical trial registries will be systematically searched for relevant studies published from inception date to 18 January 2024. No language restrictions will be applied during the search process. Two independent reviewers will identify eligible trials and extract the data. Traditional pairwise meta-analysis will be conducted to analyse direct comparisons. A frequentist approach will be used to analyse the primary outcome for network comparisons, and cumulative rank probabilities will present the treatment hierarchy of all endpoints. Sensitivity analysis will be conducted using a Bayesian framework under a random-effects model. Subgroup analyses will be conducted according to sample size, quality of study and sponsorship, if the data allow. The Cochrane Risk of Bias Tool 2.0 will be used to assess the quality of the included studies. The Grading of Recommendations, Assessment, Development, and Evaluation system will be used to assess the strength of evidence., Ethics and Dissemination: Since this study relies solely on published literature, no ethics approval is necessary. The results will be submitted to a peer-reviewed journal., Prospero Registration Number: CRD42024503239., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Wing dimorphism is a distinguishing characteristic of brown planthopper Nilaparvata lugens (Stål) populations, wherein adults exhibit 2 distinct morphs: long-winged and short-winged. The presence of long-winged individuals often heralds the onset of migration, while short-winged morphs signify high reproduction and can be associated with population outbreaks. This phenomenon underscores the adaptability of these insects in response to environmental cues and their impact on agricultural ecosystems. Wing morphs of N. lugens are controlled by genetical and environmental factors. Mate choice between long and short-winged adults affects wing morphs of offspring. In this study, we found that the wild population had no persistent preference for choosing long-winged or short-winged adults to mate. But in 2 multigenerational selected lineages for long and short-winged morphs, the short-winged males preferred to short-winged females to mate and the long-winged males had no preference. In the nearly pure-bred lineages of long-winged and short-winged morphs, both wing morphs of females preferred for short-winged males. Purification of wing morph lineages enhanced mating preference for short-winged partners. When the wing developmental gene InR1 or InR2 was interfered by RNAi, the pure-bred lineage of long-winged morph mainly produced short-winged adults and the short-winged morphs produced long-winged adults, and these adults exhibited preference to mate with short-winged partners. The tendency to mate with short-winged morphs leads to more short-winged offspring which easily causes the rapid growth of populations., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To identify whether Banxia Xiexin Decoction (BXD) alleviates cerebral glucose metabolism disorder by intestinal microbiota regulation in APP/PS1 mice., Methods: Forty-five 3-month-old male APP/PS1 mice were divided into 3 groups using a random number table (n=15 per group), including a model group (MG), a liraglutide group (LG) and a BXD group (BG). Fifteen 3-month-old male C57BL/6J wild-type mice were used as the control group (CG). Mice in the BG were administered BXD granules by gavage at a dose of 6 g/(kg•d) for 3 months, while mice in the LG were injected intraperitoneally once daily with Liraglutide Injection (25 nmol/kg) for 3 months. Firstly, liquid chromatography with tandem-mass spectrometry was used to analyze the active components of BXD granules and the medicated serum of BXD. Then, the cognitive deficits, Aβ pathological change and synaptic plasticity markers, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), were measured in APP/PS1 mice. Brain glucose uptake was detected by micropositron emission tomography. Intestinal microbial constituents were detected by 16S rRNA sequencing. The levels of intestinal glucagon-like peptide 1 (GLP-1) and cerebral GLP-1 receptor (GLP-1R), as well as the phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3β (PI3K/Akt/GSK3β) insulin signaling pathway were determined by immunohistochemical (IHC) staining and Western blot analysis, respectively., Results: BXD ameliorated cognitive deficits and Aβ pathological features (P<0.01). The expressions of SYP and PSD95 in the BG were higher than those in the MG (P<0.01). Brain glucose uptake in the BG was higher than that in the MG (P<0.01). The intestinal microbial composition in the BG was partially reversed. The levels of intestinal GLP-1 in the BG were higher than those in the MG (P<0.01). Compared with the MG, the expression levels of hippocampal GLP-1R, Akt, PI3K and p-PI3K in the BG were significantly increased (P<0.01), while the levels of GSK3β were reduced (P<0.01)., Conclusion: BXD exhibited protective effects against Alzheimer's disease by regulating the gut microbiota/GLP-1/GLP-1R, enhancing PI3K/Akt/GSK3β insulin signaling pathway, and improving brain glucose metabolism., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Human DDX3X, an important member of the DEAD-box family RNA helicases, plays a crucial role in RNA metabolism and is involved in cancer development, viral infection, and neurodegenerative disease. Although there have been many studies on the physiological functions of human DDX3X, issues regarding its exact targets and mechanisms of action remain unclear. In this study, we systematically characterized the biochemical activities and substrate specificity of DDX3X. The results demonstrate that DDX3X is a bidirectional RNA helicase to unwind RNA duplex and RNA-DNA hybrid driven by ATP. DDX3X also has nucleic acid annealing activity, especially for DNA. More importantly, it can function as a typical nucleic acid chaperone which destabilizes highly structured DNA and RNA in an ATP-independent manner and promotes their annealing to form a more stable structure. Further truncation mutations confirmed that the highly disordered N-tail and C-tail are critical for the biochemical activities of DDX3X. They are functionally complementary, with the N-tail being crucial. These results will shed new light on our understanding of the molecular mechanism of DDX3X in RNA metabolism and DNA repair, and have potential significance for the development of antiviral/anticancer drugs targeting DDX3X., Competing Interests: Declaration of Competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB., (© 2024. The Author(s).)

This study reports the rational engineering of the S1' substrate-binding pocket of a thermally-stable keratinase from Pseudomonas aeruginosa 4-3 (4-3Ker) to improve substrate specificity to typical keratinase (K/C > 0.5) and catalytic activity without compromising thermal stability for efficient keratin degradation. Of 10 chosen mutation hotspots in the S1' substrate-binding pocket, the top three mutations M128R, A138V, and V142I showing the best catalytic activity and substrate specificity were identified. Their double and triple combinatorial mutants synergistically overcame limitations of single mutants, fabricating an excellent M128R/A138V/V142I triple mutant which displayed a 1.21-fold increase in keratin catalytic activity, 1.10-fold enhancement in keratin/casein activity ratio, and a 3.13 °C increase in half-inactivation temperature compared to 4-3Ker. Molecular dynamics simulations revealed enhanced flexibility of critical amino acid residues at the substrate access tunnel, improved global protein rigidity, and heightened hydrophobicity within the active site likely underpinned the increased catalytic activity and substrate specificity. Additionally, the triple mutant improved the feather degradation rate by 32.86 % over the wild-type, far exceeding commercial keratinase in substrate specificity and thermal stability. This study exemplified engineering a typical keratinase with enhanced substrate specificity, catalytic activity, and thermal stability from thermally-stable 4-3Ker, providing a more robust tool for feather degradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Snails are important agricultural pests difficult to control, but data regarding molluscicidal assays are scant. Stemona alkaloids are typical secondary metabolites for the taxa and have been broadly investigated for their pharmacological and toxicological effects. This makes it possible for us to further develop the toxicities of these compounds to snails. In this work, we tested the antifeedant properties of leaves from seven Chinese Stemona species against the land snail species Bradybaena ravida in choice and non-choice feeding assays. The tested leaves Stemona parviflora exhibited the most deterrent effects, and a further phytochemical investigation of aerial parts led to the identification of 16 alkaloids. Among them, three novel alkaloids could be identified. The alkaloidal fraction and single alkaloids were further assayed against this snail species, and the results suggest a cocktail effect because the impact of the alkaloidal fraction was higher than the effects caused by single alkaloids. The study can promote the search process of natural antimollusc products from plants to control snails.

Objective: To evaluate the safety of early enteral nutrition (EEN) support in patients with severe intra-abdominal infection and intestinal fistulas. Methods: This was a retrospective cohort study. We collected relevant clinical data of 204 patients with severe intra-abdominal infection and intestinal fistulas who had been managed in the No. 1 Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University between 1 January 2017 and 1 January 2020. The patients were allocated to EEN or delayed enteral nutrition (DEN) groups depending on whether enteral nutrition had been instituted within 48 hours of admission to the intensive care unit. The primary outcome was 180-day mortality. Other outcomes included rates of intraperitoneal hemorrhage, septic shock, open abdominal cavity, bloodstream infection, mechanical ventilation, and continuous renal replacement therapy. Risk factors for mortality were analyzed by logistic regression. Results: There were no significant differences in hematological data or other baseline characteristics between the two groups at the time of admission to the intensive care unit (all P >0.05). However, septic shock (31.2% [15/48] vs. 15.4% [24/156], χ 2 =4.99, P =0.025), continuous renal replacement therapy (27.1% [13/48] versus 9.0% [14/156], χ 2 =8.96, P =0.003), and 180-day mortality (31.2% [15/48] vs. 7.7% [12/156], χ 2 =15.75, P <0.001) were significantly more frequent in the EEN than the DEN group (all P <0.05). Multivariate regression analysis showed that older age (OR=1.082, 95%CI:1.027-1.139, P =0.003), worse Acute Physiology and Chronic Health Evaluation (APACHE) II scores (OR=1.189, 95%CI: 1.037-1.363, P =0.013), higher C-reactive protein (OR=1.013, 95%CI:1.004-1.023, P =0.007) and EEN (OR=8.844, 95%CI:1.809- 43.240, P =0.007) were independent risk factors for death in patients with severe intra-abdominal infection and intestinal fistulas. Conclusion: EEN may lead to adverse events and increase mortality in patients with both enterocutaneous fistulas and severe abdominal infection. EEN should be implemented with caution in such patients.

Background: Citrus is one of the most valuable fruits worldwide and an economic pillar industry in southern China. Nevertheless, it frequently suffers from undesirable environmental stresses during the growth cycle, which severely restricts the growth, development and yield of citrus. In plants, the growth-regulating factor (GRF) family of transcription factors (TF) is extensively distributed and plays an vital part in plant growth and development, hormone response, as well as stress adaptation. However, the systematic identification and functional analysis of GRF TFs in citrus have not been reported., Results: Here, a genome-wide identification of GRF TFs was performed in Citrus sinensis, 9 members of CsGRFs were systematically identified and discovered to be scattered throughout 5 chromosomes. Subsequently, physical and chemical properties, phylogenetic relationships, structural characteristics, gene duplication events, collinearity and cis-elements of promoter were elaborately analyzed. In particular, the expression patterns of the CsGRF genes in response to multiple phytohormone and abiotic stress treatments were investigated. Predicated on this result, CsGRF04, which exhibited the most differential expression pattern under multiple phytohormone and abiotic stress treatments was screened out. Virus-induced gene silencing (VIGS) technology was utilized to obtain gene silenced plants for CsGRF04 successfully. After the three stress treatments of high salinity, low temperature and drought, the CsGRF04-VIGS lines showed significantly reduced resistance to high salinity and low temperature stresses, but extremely increased resistance to drought stress., Conclusions: Taken together, our findings systematically analyzed the genomic characterization of GRF family in Citrus sinensis, and excavated a CsGRF04 with potential functions under multiple abiotic stresses. Our study lay a foundation for further study on the function of CsGRFs in abiotic stress and hormone signaling response., (© 2024. The Author(s).)

Reactive oxygen species (ROS) are crucial for signal transduction and the maintenance of cellular homeostasis. However, superfluous ROS may engender chronic pathologies. Feather keratin is a promising new source of antioxidant peptides that can eliminate excess ROS and potentially treat oxidative stress-related diseases, but the underlying mechanisms have remained elusive. This study investigated the antioxidant effects and mechanisms against H 2 O 2 -induced oxidative damage in HepG2 cells of the two latest discovered antioxidant peptides, CRPCGPTP (CP-8) and ANSCNEPCVR (AR-10), first decrypted from feather keratin. The results revealed that CP-8 and AR-10 did not exhibit cytotoxicity to HepG2 cells while reducing intracellular ROS accumulation. Simultaneously, they enhanced the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), thus alleviating H 2 O 2 -induced cell apoptosis. Molecular docking analysis demonstrated that CP-8, AR-10 interacted well with the key amino acids in the Kelch domain of Keap1, thereby directly disrupting the Keap1-Nrf2 interaction. The peptides' biosafety and antioxidant activity via Keap1/Nrf2 signaling lay the groundwork for further animal studies and applications as functional food additives.

Alzheimer's disease (AD) presents a significant challenge to global healthcare systems, with current treatments offering only modest relief and often bringing unwanted side effects, necessitating the exploration of more effective and safer drugs. In this study, we employed the Caenorhabditis elegans ( C. elegans ) model, specifically the AD-like CL4176 strain expressing the human Aβ (1-42) protein, to investigate the potential of Reineckia carnea extract and its fractions. Our results showed that the Reineckia carnea ether fraction (REF) notably diminished the paralysis rates of CL4176 worms. Additionally, REF also attenuated the neurotoxicity effects prompted by Tau proteins in the BR5270 worms. Moreover, REF was observed to counteract the accumulation of Aβ and pTau proteins and their induced oxidative stress in C. elegan s AD-like models. Mechanistic studies revealed that REF's benefits were associated with the induction of autophagy in worms; however, these protective effects were nullified when autophagy-related genes were suppressed using RNAi bacteria. Together, these findings highlight Reineckia carnea ether fraction as a promising candidate for AD treatment, warranting further investigation into its autophagy-inducing components and their molecular mechanisms.

Objectives: To compare the effect of different frequency of acupoint thread-embedding on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention., Methods: A total of 126 subjects with overweight/obesity of spleen deficiency and dampness retention were randomized into a 2-week group(63 cases, 13 cases dropped out)and a 3-week group(63 cases, 11 cases dropped out, 1 case was eliminated). The two groups were treated with acupoint thread-embedding once every 2 weeks and once every 3 weeks respectively, Zhongwan(CV 12), Shuifen(CV 9), Qihai(CV 6), Guanyuan(CV 4) and bilateral Zhangmen(LR 13), Tianshu(ST 25), Liangmen(ST 21), Daheng(SP 15), Fujie(SP 14), Pishu(BL 20), Yinlingquan(SP 9)were selected. Four times were required in the two groups. Before and after treatment, follow-up after 2 months of treatment completion, the body mass index(BMI), body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, fat percentage(F%), skin fold thickness were observed in the two groups., Results: After treatment and in follow-up, the BMI, body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, F%, skin fold thickness in the two groups were decreased compared with those before treatment ( P <0.001, P <0.01), the changes of BMI, body weight, obesity degree, F%, skin fold thickness in the 2-week group were larger than those in the 3-week group( P <0.05, P <0.01, P <0.001)., Conclusions: The effect of acupoint thread-embedding once every 2 weeks on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention is superior to that once every 3 weeks.

Aconiti Lateralis Radix Praeparata polysaccharides(AP) are a class of bioactive macromolecules extracted from the herbs of Aconiti Lateralis Radix Praeparata and its various processed products. Since the AP was first separated in 1986, its pharmacological effects include immune regulation, anti-tumor, anti-depression, organ protection, hypoglycemia, and anti-inflammatory had been found. In recent years, with the development of polysaccharide extraction, separation, and structure identification technologies, more than 20 kinds of AP have been separated from Aconiti Lateralis Radix Praeparata and its processed products, and they have ob-vious differences in relative molecular weight, monosaccharide composition, glycosidic bond, structural characteristics, and biological activities. In particular, AP may be dissolved, degraded, or allosteric under the complex processing environment of fermentation, soaking, cooking, etc., leading to the diversified structure of AP, which provides a possibility for further understanding of the structure-activity relationship of AP. Therefore, this study systematically reviewed the research progress on the structure and structure-activity relationship of AP, summarized the biological activity and potential action mechanism of AP, and discussed the technical challenges in the development and application of AP, so as to promote the quality control and further development and utilization of AP.

Background: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder without an effective cure. Natural products, while showing promise as potential therapeutics for AD, remain underexplored., Aims: This study was conducted with the goal of identifying potential anti-AD candidates from natural sources using Caenorhabditis elegans (C. elegans) AD-like models and exploring their mechanisms of action., Materials & Methods: Our laboratory's in-house herbal extract library was utilized to screen for potential anti-AD candidates using the C. elegans AD-like model CL4176. The neuroprotective effects of the candidates were evaluated in multiple C. elegans AD-like models, specifically targeting Aβ- and Tau-induced pathology. In vitro validation was conducted using PC-12 cells. To investigate the role of autophagy in mediating the anti-AD effects of the candidates, RNAi bacteria and autophagy inhibitors were employed., Results: The ethanol extract of air-dried fruits of Luffa cylindrica (LCE), a medicine-food homology species, was found to inhibit Aβ- and Tau-induced pathology (paralysis, ROS production, neurotoxicity, and Aβ and pTau deposition) in C. elegans AD-like models. LCE was non-toxic and enhanced C. elegans' health. It was shown that LCE activates autophagy and its anti-AD efficacy is weakened with the RNAi knockdown of autophagy-related genes. Additionally, LCE induced mTOR-mediated autophagy, reduced the expression of AD-associated proteins, and decreased cell death in PC-12 cells, which was reversed by autophagy inhibitors (bafilomycin A1 and 3-methyladenine)., Discussion: LCE, identified from our natural product library, emerged as a valuable autophagy enhancer that effectively protects against neurodegeneration in multiple AD-like models. RNAi knockdown of autophagy-related genes and cotreatment with autophagy inhibitors weakened its anti-AD efficacy, implying a critical role of autophagy in mediating the neuroprotective effects of LCE., Conclusion: Our findings highlight the potential of LCE as a functional food or drug for targeting AD pathology and promoting human health., (© 2023 John Wiley & Sons Ltd.)

Enhancing the clearance of proteins associated with Alzheimer's disease (AD) emerges as a promising approach for AD therapeutics. This study explores the potential of Radix Stellariae, a traditional Chinese medicine, in treating AD. Utilizing transgenic C. elegans models of AD, we demonstrated that a 75% ethanol extract of Radix Stellariae (RSE) (at 50 µg/mL) effectively diminishes Aβ and Tau protein expression, and alleviates their induced impairments including paralysis, behavioral dysfunction, neurotoxicity, and ROS accumulation. Additionally, RSE enhances the stress resistance of C. elegans. Further investigations revealed that RSE promotes autophagy, a critical cellular process for protein degradation, in these models. We found that inhibiting autophagy-related genes negated the neuroprotective effects of RSE, suggesting a central role for autophagy in the actions of RSE. In PC-12 cells, we observed that RSE not only inhibited Aβ fibril formation but also promoted the degradation of AD-related proteins and reduced their cytotoxicity. Mechanistically, RSE was found to induce autophagy via modulating PI3K/AKT/mTOR and AMPK/mTOR signaling pathways. Importantly, inhibiting autophagy counteracted the beneficial effects of RSE on the clearance of AD-associated proteins. Moreover, we identified Dichotomine B, a β-carboline alkaloid, as a key active constituent of RSE in mitigating AD pathology in C. elegans at concentrations ranging from 50 to 1000 µM. Collectively, our study presents novel discoveries that RSE alleviates AD pathology and toxicity primarily by inducing autophagy, both in vivo and in vitro. These findings open up new avenues for exploring the therapeutic potential of RSE and its active component, Dichotomine B, in treating neurodegenerative diseases like AD., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Acute kidney injury (AKI) is characterized by a rapid decrease in renal function with high mortality and risk of progression to chronic kidney disease (CKD). Ischemia and reperfusion injury (IRI) is one of the major causes of AKI. However, the cellular and molecular responses of the kidney to IRI are complex and not fully understood. Herein, we conducted unbiased proteomics and bioinformatics analyses in an IRI mouse model on days 3, 7, and 21, and validated the results using IRI, unilateral ureteral obstruction (UUO), and biopsies from patients with AKI or CKD. The results indicated an obvious temporal expression profile of differentially expressed proteins and highlighted impaired lipid metabolism during the progression of AKI to CKD. Acyl-coenzyme A oxidase 1 (Acox1), the first rate-limiting enzyme of peroxisomal fatty acid beta-oxidation, was then selected, and its disturbed expression in the two murine models validated the proteomic findings. Accordingly, Acox1 expression was significantly downregulated in renal biopsies from patients with AKI or CKD, and its expression was negatively correlated with kidney injury score. Furthermore, in contrast to the decreased Acox1 expression, lipid droplet accumulation was remarkably increased in these renal tissues, suggesting dysregulation of fatty acid oxidation. In conclusion, our results suggest that defective peroxisomal fatty acid oxidation might be a common pathological feature in the transition from AKI to CKD, and that Acox1 is a promising intervention target for kidney injury and repair., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors.)

In this study, the crude polysaccharides was extracted from Shengfupian and purified by Sevag deproteinization. Then, the purified neutral polysaccharide fragment was obtained by the DEAE-52 cellulose chromatography column and Sephadex G-100 co-lumn. The structure of polysaccharides was characterized by ultraviolet spectroscopy, infrared spectroscopy, ion chromatography, and gel permeation chromatography. To investigate the anti-inflammatory activity of Shengfupian polysaccharides, LPS was used to induce inflammation in RAW264.7 cells. The expression of the CD86 antibody on surface of M1 cells, the function of macrophages, and the content of NO and IL-6 in the supernatant were examined. An immunodepression model of H22 tumor-bearing mice was established, and the immunomodulatory activity of Shengfupian polysaccharides was evaluated based on the tumor inhibition rate, immune organ index and function, and serum cytokine levels. Research indicated that Shengfupian polysaccharides(80 251 Da) was composed of arabinose, galactose, glucose, and fructose with molar ratio of 0.004∶0.018∶0.913∶0.065. It was smooth and lumpy under the scanning electron microscope. In the concentration range of 25-200 μg·mL~(-1), Shengfupian polysaccharides exhibited little or no toxicity to RAW264.7 cells and could inhibit the polarization of cells to the M1 type and reduce the content of NO and IL-6 in the cell supernatant. It could suppress the phagocytosis of cells at the concentration of 25 μg·mL~(-1), while enhancing the phagocytosis of RAW264.7 cells within the concentration range of 100-200 μg·mL~(-1). The 200 mg·kg~(-1) Shengfupian polysaccharides could alleviate the spleen injury caused by cyclophosphamide, increase the levels of IL-1β and IL-6, and decrease the level of TNF-α in the serum of mice. In conclusion, Shengfupian polysaccharides has anti-inflammatory effect and weak immunomodulatory effect, which may the material basis of Aconm Lateralis Radix Praeparaia for dispelling cold and relieving pain.

Background: To analyze the clinicopathological features of different histological subtypes of epulis, and evaluate the risk factors associated with recurrence., Materials and Methods: A retrospective study including 2971 patients was performed. The patients' sex, age, location, size, histological subtypes, recurrence information, oral hygiene habits, periodontitis symptoms and smoking history were retrieved from the patient medical records and follow-up information., Results: Among the 2971 cases, focal fibrous hyperplasia (FFH) was the most common lesion (60.92%), followed by peripheral ossifying fibroma (POF) (29.32%), pyogenic granuloma (PG) (8.08%) and peripheral giant cell granuloma (PGCG) (1.68%). The peak incidence of epulis was in the third and fourth decade of life, with a mean age of 45.55 years. Female predominance was found in all types of lesions with a female to male ratio of 1.71:1. PG had the highest recurrence rate (17.18%), followed by POF (12.98%), FFH (9.55%) and PGCG (8.82%). Histological subtypes were significantly correlated with the recurrence of epulis (P = 0.013). Regular supportive periodontal therapy (P = 0.050) had a negative correlation with recurrence, whereas symptoms of periodontitis (P < 0.001) had a positive correlation with the recurrence of epulis., Conclusions: Controlling the periodontal inflammation and regular supportive periodontal therapy might help reduce the recurrence of epulis., (© 2023. The Author(s).)

Objective: To estimate the risk for type 2 diabetes mellitus (T2DM) death attributed to insufficient whole grain intake in seven regions of China from 2005 to 2018. Methods: Based on China National Nutrition and Health Surveys and China Adult Chronic Disease and Nutrition Surveillance, ordinary Kriging method and locally weighted regression were used to estimate the level of whole grain intake of Chinese residents from 2005 to 2018. Based on the results of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 and Chronic Diseases Risk Factors Surveillance in China, we calculated the population attributable fraction (PAF), attributable death number and attributable mortality rate of T2DM due to insufficient whole grain intake in people aged ≥20 years in different regions of China, and we used the 2010 Chinese census data to compare the changes in T2DM deaths attributed to insufficient intake of whole grains in seven regions of China. Results: The whole grain intake levels of Chinese people over 20 years old in 2002, 2010 and 2015 were 19.0 g/d, 14.3 g/d and 19.8 g/d, respectively. The estimated overall whole grain intake level was 20.1 g/d in Chinese residents in 2018, and the intake level was 19.4 g/d in men and 20.8 g/d in women. Among the seven regions, the intake level was highest in northern China (47.4 g/d) and lowest in southwestern China (6.0 g/d). In 2018, the PAF was lowest in northern China (12.8%) and highest in southwestern China (19.3%). From 2005 to 2018, the PAF varied in the seven regions, and the PAF in northeastern China fluctuated around 18.5%. Other regions showed downward trends, especially in northern China and northwestern China, decreased by 26.4% and 21.2%, respectively. Over the past 14 years, the number of attributable deaths in the seven regions showed upward trends, with the highest annual average growth rate of 6.7% in southern China and the lowest annual average growth rate of 2.4% in northern China. In 2018, the standardized T2DM mortality rate attributed to insufficient whole grain intake in China was 3.13/100 000, and the attributable mortality was 3.21/100 000 in men and 3.05/100 000 in women. The standardized attributable mortality rate was highest in southwestern China (3.97/100 000) and lowest in northern China (1.78/100 000). From 2005 to 2018, the standardized attributable mortality rate increased by 11.5% in men and decreased by 8.1% in women. The standardized attributable mortality rate in southwestern, southern and central China increased by 23.7%, 21.3% and 4.2%, respectively. The standardized attributable mortality rate in northern, northwestern, eastern and northeastern China decreased by 20.9%, 11.0%, 4.5% and 3.9%, respectively. Conclusion: The whole grain intake level of Chinese residents was low, and the whole grain intake of residents in all seven regions should be increased, especially in the southwest, and men should have more whole grain intake than women to reduce the death risk in patients with T2DM.

Objective: To describe the prevalence of alcohol consumption and the burden of hemorrhagic stroke and hypertensive heart disease attributed to alcohol consumption in adults aged ≥20 years in 31 provinces in China from 2005 to 2018. Methods: Data from several national representative surveys was used to estimate provincial alcohol exposure level of adults aged ≥20 years from 2005 to 2018 by using kriging interpolation and locally weighted regression methods. Global disease burden research method and data, and China's death cause surveillance data were used to calculate the population attributable fraction (PAF) of hemorrhagic stroke and hypertensive heart disease and the deaths due to alcohol consumption in men and women aged ≥20 years in 31 provinces in China. China census data of 2010 were used to calculate the attributable standardized mortality rate. Results: In 2005 and 2018, the prevalence of alcohol consumption was 58.7% (95% CI : 57.8%-59.5%) and 58.4% (95% CI : 57.6%-59.3%), respectively, in men and 17.0% (95% CI : 16.6%-17.4%) and 18.7% (95% CI :18.1%-19.3%), respectively, in women. The daily alcohol intake was 24.6 (95% CI : 23.8-25.3) g and 27.7 (95% CI : 26.8-28.7) g, respectively, in men and 6.3 (95% CI : 6.0-6.5) g and 5.3 (95% CI : 5.0-5.6) g, respectively, in women. Alcohol exposure level was higher in the provinces in central and eastern China than in western provinces. The lowest exposure level was found in northwestern provinces. From 2005 to 2018, the PAF of hemorrhagic stroke death due to alcohol consumption increased from 5.5% to 6.8%, the attributable deaths increased from 50 200 to 59 100, while the PAF of hypertensive heart disease death due to alcohol consumption increased from 7.0% to 7.7%, the attributable deaths increased from 15 200 to 29 300. The PAF of hypertensive heart disease and hemorrhagic stroke was higher in men than in women, and in central and eastern provinces than in western provinces. In 2018, the standardized mortality rates of hemorrhagic stroke and hypertensive heart disease attributed to alcohol consumption were 4.58/100 000 and 2.11/100 000, respectively. Conclusions: The prevalence of alcohol consumption in men and daily alcohol intake of drinkers were relatively high in China, especially in eastern provinces. Alcohol exposure level was lower in women than in men. Regional measures should be taken to reduce the alcohol intakes in men and current drinkers in order to reduce the health problems caused by alcohol consumption.

Polybrominated diphenyl ethers (PBDEs) are classic and emerging pollutants that are potentially harmful to the human immune system. Research on their immunotoxicity and mechanisms suggests that they play an important role in the resulting pernicious effects of PBDEs. 2,2',4,4'-Tetrabrominated biphenyl ether (BDE-47) is the most biotoxic PBDE congener, and, in this study, we evaluated its toxicity toward RAW264.7 cells of mouse macrophages. The results show that exposure to BDE-47 led to a significant decrease in cell viability and a prominent increase in apoptosis. A decrease in mitochondrial membrane potential (MMP) and an increase in cytochrome C release and caspase cascade activation thus demonstrate that cell apoptosis induced by BDE-47 occurs via the mitochondrial pathway. In addition, BDE-47 inhibits phagocytosis in RAW264.7 cells, changes the related immune factor index, and causes immune function damage. Furthermore, we discovered a significant increase in the level of cellular reactive oxygen species (ROS), and the regulation of genes linked to oxidative stress was also demonstrated using transcriptome sequencing. The degree of apoptosis and immune function impairment caused by BDE-47 could be reversed after treatment with the antioxidant NAC and, conversely, exacerbated by treatment with the ROS-inducer BSO. These findings indicate that oxidative damage caused by BDE-47 is a critical event that leads to mitochondrial apoptosis in RAW264.7 macrophages, ultimately resulting in the suppression of immune function.

Objective: To investigate the effect of adipocytes in the bone marrow microenvironment of patients with multiple myeloma (MM) on the pathogenesis of MM., Methods: Bone marrow adipocytes (BMA) in bone marrow smears of health donors (HD) and newly diagnosed MM (ND-MM) patients were evaluated with oil red O staining. The mesenchymal stem cells (MSC) from HD and ND-MM patients were isolated, and in vitro co-culture assay was used to explore the effects of MM cells on the adipogenic differentiation of MSC and the role of BMA in the survival and drug resistance of MM cells. The expression of adipogenic/osteogenic differentiation-related genes PPAR-γ , DLK1 , DGAT1 , FABP4 , FASN and ALP both in MSC and MSC-derived adipocytes was determined with real-time quantitative PCR. The Western blot was employed to detect the expression levels of IL-6, IL-10, SDF-1α, TNF-α and IGF-1 in the supernatant with or without PPAR-γ inhibitor., Results: The results of oil red O staining of bone marrow smears showed that BMA increased significantly in patients of ND-MM compared with the normal control group, and the BMA content was related to the disease status. The content of BMA decreased in the patients with effective chemotherapy. MM cells up-regulated the expression of MSC adipogenic differentiation-related genes PPAR-γ , DLK1 , DGAT1 , FABP4 and FASN , but the expression of osteogenic differentiation-related gene ALP was significantly down-regulated. This means that the direct consequence of the interaction between MM cells and MSC in the bone marrow microenvironment is to promote the differentiation of MSC into adipocytes at the expense of osteoblasts, and the cytokines detected in supernatant changed. PPAR-γ inhibitor G3335 could partially reverse the release of cytokines by BMA. Those results confirmed that BMA regulated the release of cytokines via PPAR-γ signal, and PPAR-γ inhibitor G3335 could distort PPAR-γ mediated BMA maturation and cytokines release. The increased BMA and related cytokines effectively promoted the proliferation, migration and drug resistance of MM cells., Conclusion: The BMA and its associated cytokines are the promoting factors in the survival, proliferation and migration of MM cells. BMA can protect MM cells from drug-induced apoptosis and plays an important role in MM treatment failure and disease progression.

Background: Protein aggregates are considered key pathological features in neurodegenerative diseases (NDs). The induction of autophagy can effectively promote the clearance of ND-related misfolded proteins., Objective: In this study, we aimed to screen natural autophagy enhancers from traditional Chinese medicines (TCMs) presenting potent neuroprotective potential in multiple ND models., Methods: The autophagy enhancers were broadly screened in our established herbal extract library using the transgenic Caenorhabditis elegans (C. elegans) DA2123 strain. The neuroprotective effects of the identified autophagy enhancers were evaluated in multiple C. elegans ND models by measuring Aβ-, Tau-, α-synuclein-, and polyQ40-induced pathologies. In addition, PC-12 cells and 3 × Tg-AD mice were employed to further validate the neuroprotective ability of the identified autophagy enhancers, both in vitro and in vivo. Furthermore, RNAi bacteria and autophagy inhibitors were used to evaluate whether the observed effects of the identified autophagy enhancers were mediated by the autophagy-activated pathway., Results: The ethanol extract of Folium Hibisci Mutabilis (FHME) was found to significantly increase GFP::LGG-1-positive puncta in the DA2123 worms. FHME treatment markedly inhibited Aβ, α-synuclein, and polyQ40, as well as prolonging the lifespan and improving the behaviors of C. elegans, while siRNA targeting four key autophagy genes partly abrogated the protective roles of FHME in C. elegans. Additionally, FHME decreased the expression of AD-related proteins and restored cell viability in PC-12 cells, which were canceled by cotreatment with 3-methyladenine (3-MA) or bafilomycin A1 (Baf). Moreover, FHME ameliorated AD-like cognitive impairment and pathology, as well as activating autophagy in 3 × Tg-AD mice., Conclusion: FHME was successfully screened from our natural product library as a potent autophagy enhancer that exhibits a neuroprotective effect in multiple ND models across species through the induction of autophagy. These findings offer a new and reliable strategy for screening autophagy inducers, as well as providing evidence that FHME may serve as a possible therapeutic agent for NDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that there are no competing interests associated with the manuscript., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Nutrition intervention has emerged as a potential strategy to delay aging and promote healthy longevity. Citri Reticulatae Semen (CRS) has diverse beneficial effects and has been used for thousands of years to treat pain. However, the health benefits of CRS in prolonging health span and improving aging-related diseases and the exact mechanisms remain poorly characterized. In this study, Caenorhabditis elegans (C. elegans) was used as a model organism to study the antiaging and health span promoting activities of 75% ethanol extract of CRS (CRSE). The results showed that treatment with CRSE at 1 000 μg/mL significantly extended the life span of worms by 18.93% without detriment to health span and fitness, as evidenced by the delayed aging-related phenotypes and increased body length and width, and reproductive output. In addition, CRSE treatment enhanced the ability of resistance to heat, oxidative, and pathogenic bacterial stress. Consistently, heat shock proteins and antioxidant enzyme-related and pathogenesis-related genes were up-regulated by CRSE treatment. Furthermore, CRSE supplementation also improved α-synuclein, 6-OHDA, and polyQ40-induced pathologies in transgenic C. elegans models of Parkinson's disease and Huntington's disease. The mechanistic study demonstrated that CRSE induced autophagy in worms, while the RNAi knockdown of 4 key autophagy-related genes, including lgg-1, bec-1, vps-34, and unc-51, remarkably abrogated the beneficial effects of CRSE on the extending of life span and health span and neuroprotection, demonstrating that CRSE exerts beneficial effects via autophagy induction in worms. Together, our current findings provide new insights into the practical application of CRS for the prevention of aging and aging-related diseases., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Plastic pollution is a global concern and an issue in environmental governance. Based on the updated "Plastic Prohibition/Restriction Order" issued recently in China, the present study systematically reviewed the implementation effectiveness of the "Plastic Prohibition/Restriction Order" since 2007. Furthermore, we summarized plastics in China and plastic waste management progress policies. Additionally, three deficiencies of the updated "Plastic Prohibition/Restriction Order" were discussed:policy formulation, implementation, and supervision. Some positive recommendations were provided based on the available reports, such as integrating plastic pollution into national basic laws and regulation systems, building a network platform for public attendance, and coordinating the publicity of the "Plastic prohibition/Restriction Order" with the public interest. Besides these measurements, some points about plastic waste management in the future were also highlighted, such as the "blind area" in small retail stores, the rational sharing of environmental protection responsibility, new materials and processes, and recycling and disposal systems for plastic wastes. Most importantly, the present study could provide ideas for policy-makers to address plastic pollution at its sources.

Many Chinese medicinal materials, vegetable oils and extracts, and even Chinese patent medicines are spicy, which influences the medication compliance of patients, especially children. Different from the sour, sweet, bitter, salty, and umami tastes, it is a painful sensation formed when the spicy substances stimulate the nerve endings. At the moment, there are a few studies on the spicy components and mechanism and masking technology for the spicy flavor of Chinese medicine in the pharmaceutical industry, and the findings in food science are usually taken as a reference, which fail to guide the masking of the spicy flavor in Chinese medicine preparations. According to literature research, the exterior-releasing medicine, dampness-resolving medicine, and interior-warming medicine are spicy, especially some vegetable oils and extracts. Taking Zingiberis Rhizoma and prescriptions containing this medicinal as an example, the spicy components in Chinese medicine and the structure-activity characteristics were analyzed to reveal the mechanism for the spicy flavor: spicy components activate the transient receptor potential vanilloid subfamily member 1(TRPV1). The advantages and disadvantages of separation, neutralization with sugar, and inclusion for the masking of the spicy flavor were summarized and the applicability in Chinese medicine was analyzed. Moreover, the future development direction was put forward. This study is expected to promote the development of spicy masking technology for Chinese medicine prescriptions for children.

The glymphatic system is a recently discovered glial-dependent macroscopic interstitial waste clearance system that promotes the efficient elimination of soluble proteins and metabolites from the central nervous system. Its anatomic foundation is the astrocytes and aquaporin-4 (AQP4) water channels on the endfeet of astrocytes. The aim of this study is to evaluate the plasticity of the spinal glymphatic system in male SD rats with painful diabetic neuropathy (PDN) induced by type 2 diabetes mellitus. PDN rats were modeled under a high-fat and high-glucose diet with a low dose of streptozotocin. MRI was applied to observe the infiltration and clearance of contrast to indicate the functional variability of the glymphatic system at the spinal cord level. The paw withdrawal threshold was used to represent mechanical allodynia. The numerical change of glial fibrillary acidic protein (GFAP) positive astrocytes was assessed and the polarity reversal of AQP4 protein was measured by immunofluorescence. As a result, deceased contrast infiltration and clearance, enhanced mechanical allodynia, increased number of GFAP positive astrocytes, and reversed polarity of AQP4 protein were found in the PDN rats. The above molecular level changes may contribute to the impairment of the spinal glymphatic system in PDN rats. This study revealed the molecular and functional variations of the spinal glymphatic system in PDN rats and for the first time indicated that there might be a correlation between the impaired spinal glymphatic system and PDN rats., (© 2022 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Galli Gigerii Endothelium Corneum(GGEC) is commonly used for the clinical treatment of indigestion, vomiting, diarrhea, and infantile malnutrition with accumulation. In recent decades, omnivorous domestic chickens, the original source of GGEC, has been replaced by broilers, which may lead to significant changes in the quality of the yielding GGEC. Through subjective and objective sensory evaluation, biological evaluation, and chemical analysis, this study compared the odor and quality between GGEC derived from domestic chickens and that from broilers. The odor intensity between them was compared by odor profile analysis and it was found that the fishy odor of GGEC derived from domestic chickens was significantly weaker than that of GGEC from broilers. Headspace-solid phase microextraction-gas chromatography-triple quadrupole tandem mass spectrometry(HS-SPME/GC-QQQ-MS/MS) suggested that the overall odor-causing chemicals were consistent with the fishy odor-causing chemicals. According to the odor activity va-lue and the orthogonal partial least squares discriminant analysis(OPLS-DA) result, dimethyl trisulfide, 2-methoxy-3-isobutylpyrazine, and 2-methylisoborneol were responsible for the fishy odor(OAV≥1) and the content of fishy odor-causing chemicals in GGEC derived from broilers was 1.12-2.13 folds that in GGEC from domestic chickens. The average pepsin potency in GGEC derived from broilers was 15.679 U·mg~(-1), and the corresponding figure for the medicinal from domestic chickens was 26.529 U·mg~(-1). The results of pre-column derivatization reverse-phase high-performance liquid chromatography(RP-HPLC) assay showed that the content of total amino acids and digestion-promoting amino acids in domestic chickens-derived GGEC was 1.12 times and 1.15 times that in GGEC from broilers, and the bitter amino acid content was 1.21 times folds that of the latter. In conclusion, GGEC derived from domestic chickens had weaker fishy odor, stronger enzyme activity, higher content of digestion-promoting amino acids, and stronger bitter taste than GGEC from broilers. This study lays a scientific basis for studying the quality variation of GGEC and provides a method for identifying high-quality GGEC. Therefore, it is of great significance for the development and cultivation of GGEC as both food and medicine and breeding of corresponding varieties.

Hepatocellular carcinoma (HCC) is the most prevalent type of primary liver cancer characterized by high mortality and morbidity rate. The lack of effective treatments and the high frequency of recurrence lead to poor prognosis of patients with HCC. Therefore, it is important to develop robust prediction tools for predicting the prognosis of HCC. Recent studies have shown that cancer stem cells (CSC) participate in HCC progression. The aim of this study was to explore the prognostic value of CSC-related genes and establish a prediction model based on data from The Cancer Genome Atlas (TCGA) database. In this study, 475 CSC-related genes were obtained from the Molecular Signature Database and 160 differentially expressed CSC-related genes in HCC patients were identified using the limma R package in the TCGA database. A total of 79 CSC-related genes were found to be associated with overall survival (OS). Using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions, a 3-gene signature ( RAB10 , TCOF1, and PSMD14 ) was constructed. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were constructed to test the prediction performance of the signature. Performance of the signature was validated using the International Cancer Genome Consortium (ICGC) dataset. In addition, immune feature and functional enrichment analyses were carried out to explore the underlying mechanisms. Moreover, a co-expression network was constructed using the weighted gene correlation network analysis (WGCNA) method to select genes significantly associated with risk scores in HCC in the TCGA dataset. The SGO2 gene was found to be significantly associated with risk scores of HCC. In vitro experiments revealed that it can promote HCC cell proliferation. Therefore, SGO2 may be a potential therapeutic target for HCC treatment. The constructed nomogram can help clinicians make decisions about HCC treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liang, Zhang, He, Liu, Ding, Zhang, Dong and Du.)

Apoptotic resistance leads to persistent accumulation of senescent cells and sustained expression of a senescence-associated secretory phenotype, playing an essential role in the progression of tissue fibrosis. However, whether senescent renal tubular epithelial cells (RTECs) exhibit an apoptosis-resistant phenotype, and the role of this phenotype in diabetic nephropathy (DN) remain unclear. Our previous study was the first to demonstrate that decoy receptor 2 (DcR2) is associated with apoptotic resistance in senescent RTECs and renal fibrosis. In this study, we aimed to further explore the mechanism of DcR2 in apoptosis-resistant RTECs and renal fibrosis in DN. DcR2 was co-localized with fibrotic markers (α-SMA, collagen IV, fibronectin), senescent marker p16, and antiapoptotic proteins FLIP and Bcl2 but rarely co-localized with caspase 3 or TUNEL. DcR2 overexpression promoted renal fibrosis in mice with streptozotocin (STZ)-induced DN, as evidenced by augmented Masson staining and upregulated expression of fibrotic markers. DcR2 overexpression also enhanced FLIP expression while reducing the expression of pro-apoptotic proteins (caspases 8 and 3) in senescent RTECs, resulting in apoptotic resistance. In contrast, DcR2 knockdown produced the opposite effects in vitro and in vivo. Moreover, quantitative proteomics and co-immunoprecipitation experiments demonstrated that DcR2 interacted with glucose-related protein 78 kDa (GRP78), which has been shown to promote apoptotic resistance in cancer. GRP78 exhibited co-localization with senescent and antiapoptotic markers but was rarely co-expressed with caspase 3 or TUNEL. Additionally, GRP78 knockdown decreased the apoptosis resistance of HG-induced senescent RTECs with upregulated cleaved caspase 3 and increased the percentage of apoptotic RTECs. Mechanistically, DcR2 mediated apoptotic resistance in senescent RTECs by enhancing GRP78-caspase 7 interactions and promoting Akt phosphorylation. Thus, DcR2 mediated the apoptotic resistance of senescent RTECs and renal fibrosis by interacting with GRP78, indicating that targeting the DcR2-GRP78 axis represents a promising therapeutic strategy for DN., (© 2022. The Author(s).)

Nitrate allocation in Arabidopsis (Arabidopsis thaliana) represents an important mechanism for mediating plant environmental adaptation. However, whether this mechanism occurs or has any physiological/agronomic importance in the ammoniphilic plant rice (Oriza sativa L.) remains unknown. Here, we address this question through functional characterization of the Nitrate transporter 1/Peptide transporter Family (NPF) transporter gene OsNPF7.9. Ectopic expression of OsNPF7.9 in Xenopus oocytes revealed that the gene encodes a low-affinity nitrate transporter. Histochemical and in-situ hybridization assays showed that OsNPF7.9 expresses preferentially in xylem parenchyma cells of vasculature tissues. Transient expression assays indicated that OsNPF7.9 localizes to the plasma membrane. Nitrate allocation from roots to shoots was essentially decreased in osnpf7.9 mutants. Biomass, grain yield, and nitrogen use efficiency (NUE) decreased in the mutant dependent on nitrate availability. Further analysis demonstrated that nitrate allocation mediated by OsNPF7.9 is essential for balancing rice growth and stress tolerance. Moreover, our research identified an indica-japonica divergent single-nucleotide polymorphism occurring in the coding region of OsNPF7.9, which correlates with enhanced nitrate allocation to shoots of indica rice, revealing that divergent nitrate allocation might represent an important component contributing to the divergent NUE between indica and japonica subspecies and was likely selected as a favorable trait during rice breeding., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: It is unclear whether G protein-coupled receptor 61 (GPR61) affecting body weight, plays a role in the association between birth weight and weather. This study aimed to assess the effects of prenatal weather and GPR61 on birth weight., Methods: A total of 567 mother-newborn pairs were recruited in Houzhai Center Hospital during 2011-2012. We detected the maternal and neonatal GPR61 promoter methylation levels, and obtained meteorological and air pollution data., Results: A positive association was observed between maternal and neonatal GPR61 methylation levels, and both of them were affected by precipitation, relative humidity (RH) and daily temperature range (DTR). Birth weight was associated negatively with RH and positively with DTR ( P < 0.05). A significant association was observed between birth weight and neonatal GPR61 methylation. We observed that maternal GPR61 methylation seemed to modify associations between weather and birth weight ( P interaction < 0.10), while neonatal GPR61 methylation mediated the effects of RH and DTR on birth weight ( P < 0.05)., Conclusions: Our findings revealed the significant associations among prenatal weather, GPR61 methylation and birth weight. Maternal GPR61 methylation may modify the susceptibility of birth weight to prenatal weather conditions, while neonatal GPR61 methylation may be a bridge of the effects of prenatal RH and DTR on birth weight., (Copyright © 2022 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Parkinson's disease (PD) is a complex neurological disorder characterized by motor and nonmotor features. Although some drugs have been developed for the therapy of PD in a clinical setting, they only alleviate the clinical symptoms and have yet to show a cure. In this study, by employing the C. elegans model of PD, we found that ferulic acid (FA) significantly inhibited α -synuclein accumulation and improved dyskinesia in NL5901 worms. Meanwhile, FA remarkably decreased the degeneration of dopaminergic (DA) neurons, improved the food-sensing behavior, and reduced the level of reactive oxygen species (ROS) in 6-OHDA-induced BZ555 worms. The mechanistic study discovered that FA could activate autophagy in C. elegans , while the knockdown of 3 key autophagy-related genes significantly revoked the neuroprotective effects of FA in α -synuclein- and 6-OHDA-induced C. elegans models of PD, demonstrating that FA exerts an anti-PD effect via autophagy induction in C. elegans . Furthermore, we found that FA could reduce 6-OHDA- or H 2 O 2 -induced cell death and apoptosis in PC-12 cells. Moreover, FA was able to induce autophagy in stable GFP-RFP-LC3 U87 cells and PC-12 cells, while bafilomycin A1 (Baf, an autophagy inhibitor) partly eliminated the protective effects of FA against 6-OHDA- and H 2 O 2 -induced cell death and ROS production in PC-12 cells, further confirming that FA exerts an anti-PD effect via autophagy induction in vitro. Collectively, our study provides novel insights for FA as a potent autophagy enhancer to effectively prevent neurodegenerative diseases such as PD in the future., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Tao Long et al.)

Background: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients., Methods: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80., Results: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010)., Conclusions: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality., (© 2021 S. Karger AG, Basel.)

Objective: To investigate the effect of gap junction intercellular communication (GJIC) combined by connexin43 (Cx43) and its signal to the biobehavior of multiple myeloma (MM) cells, and its possible mechanism., Methods: The mesenchymal stem cell (MSC) cells were isolated and cultured from patients with MM and normal donors. The expression of connexin43 (Cx43) in MSC cells from different sources was detected by RT-PCR and Western blot. The side population (SP) cells were sorted by flow cytometry (FCM). The effect of MSC cells from different sources to the cell cycle, Cx43 expression, colony formation in vitro, stem cell related genes expression, cytokines secretion and chemoresistance in MM SP cells as well as with or without Cx43 inhibitor 18α-glycyrrhetinic acid (18α-GA) was observed., Results: There was no significantly difference between the MSC isolated from normal donor and MM patients. Western blot showed that Cx43 expression in SP cells was up-regulated when the cells were incubated with MSC, and medium containing 18α-GA could partially inhibit it, moreover, it was more significant in MSC cells of MM patients. The ability of colony formation of SP cells in vitro was higher than those of MM cells and MM-MSC could promote the colony formation in a co-culture manner. The effect of MM-MSC to SP cells was down-regulated after 18α-GA was added. RT-PCR showed that there was several important stem cell-related genes including c-myc, Oct-4 Klf-4, and Sox-2 were found in RPMI 8226 cells, but those cells were up-regulated in SP cells (P<0.001). Meanwhile, MM-MSC could up-regulate the expression of c-myc, Klf-4 and Sox-2 (P<0.001), but down-regulate Oct-4 gene in the SP cells. The expression of those genes decreased after 18α-GA was added, but showed no significant difference (P>0.05). Cytometry bead array assays showed that MM-MSCs could secrete high level of IL-6, but the levels of IL-6, IL-10 and TGF-β increased significantly when the MM-MSCs were co-cultured with SP cells (P<0.05), especially the levels of IL-6 and IL-10 were significantly higher than cultured alone. There was no significant change in the levels of bFGF and IL-17 before and after co-cultured. The levels of IL-6, IL-10 and TGF-β in supernatant decreased significantly after GJ inhibitor 18α-GA was added. PI/Annexin V assay showed that MM cells were sensitive to bortezomib (BTZ)-induced apoptosis, but the sensitivity for SP cells was weaker. The ratio of cell apoptosis was 75.2%±0.77% and 8.12%±0.86% (P<0.001), respectively. MM-MSC could down-regulate the cell apoptosis induced by BTZ, while the sensitivity of MM cells to BTZ could be partially recovered after GJ inhibitor was added., Conclusion: MSC derived from MM patients can enhance GJIC to maintain its "hematopoiesis" by up-regulating the expression of Cx43 in MM cells, and at the same time promote cell proliferation and drug recistance by secreting multiple cytokines, which finally contributes to the relapse of MM.

Background: Even mild renal disease is a powerful cardiovascular risk factor. However, the association between these pathophysiologic processes (especially in the early asymptomatic stage) is not known., Methods: We recruited 243 asymptomatic patients with Stages 1-4 chronic kidney disease (CKD) without obstructive coronary artery disease (CAD). We distinguished different degrees of severity of intrarenal arterial lesions (IALs) according to the Oxford classification. Myocardial microcirculation perfusion was measured using single-photon emission computed tomography (SPECT). Summed scores of 17 stress and rest image segments produced the summed stress score (SSS) and summed rest score (SRS), respectively. The summed difference score (SDS) was calculated as the difference between the SSS and SRS. Coronary microvascular disease (CMD) was defined as abnormal SPECT (SSS ≥4 or SDS ≥2) in the absence of obstructive CAD., Results: Participants showed a stepwise increase in CMD severity with IAL aggravation. SSS of no/mild/moderate/severe IALs was 1.64 ± 1.08, 2.56 ± 1.35, 4.42 ± 2.17 and 6.48 ± 3.52, respectively (P < 0.05 for all). SDS of no/mild/moderate/severe IALs was 1.29 ± 0.49, 1.75 ± 0.56, 3.06 ± 1.12 and 4.16 ± 1.85, respectively (P < 0.05 for all). The percentage of subclinical CMD in CKD patients with IALs was significantly higher than in those without IALs (69.57% versus 14.71%; P = 0.01). Multiple regression analysis showed that renal arteriolar hyalinization (odds ratio = 1.578, P = 0.009) was associated independently with subclinical CMD., Conclusions: We demonstrated, for the first time, that impaired perfusion in the myocardial microcirculation in asymptomatic patients with Stages 1-4 CKD with IALs. Renal arteriolar hyalinization may be a useful marker of CMD in CKD., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

The influence of human genetic variants on the vaginal bacterial traits (VBTs) of pregnant women is still unknown. Using a genome-wide association approach based on the 16S rRNA bacteriome analysis, a total of 72 host genetic variant (single nucleotide polymorphisms [SNPs], indels, or copy number variations [CNVs])-VBT associations were found that reached the genome-wide significance level ( P  < 5 × 10 -8 ) with an acceptable genomic inflation factor λ of <1.1. The majority of these SNPs that reached the genome-wide significance level had a relatively low minor allele frequency (MAF), and only seven of them had MAFs greater than 0.05. rs303212, located at the IFIT1 gene on chromosome 10, was the most eye-catching variant, which had a genome-wide association with the relative abundance (RAB) of Actinobacteria and Bifidobacteriaceae and also had a suggestive association with the RAB of a few common vaginal bacteria including Actinobacteriota , Firmicutes , Lactobacillus , and Gardnerella vaginalis and the beta diversity weighted UniFrac ( P  < 1 × 10 -5 ). The findings of the study suggest that the vaginal bacteriome may be influenced by a number of genetic variants across the human genome and that interferon signaling may have an important influence on vaginal bacterial communities during pregnancy. IMPORTANCE Knowledge about the influence of host genetics on the vaginal bacteriome in pregnancy is still limited. Although a number of environmental and behavioral factors may exert influences on the structure of vaginal bacterial communities, the vaginal bacteriome often undergoes a relatively fixed transition to a more stable and less diverse state as the menstrual cycle stops, which raises questions on the effects of human genetics. We utilized a genome-wide approach to identify the associations between genetic variants and multiple VBTs and performed enrichment analyses. The human genetics during pregnancy may be involved in multiple pathways. The results may disclose innate functional factors involved in shaping the vaginal bacteriome during pregnancy and provide insight into the establishment of specific strategies for prevention and clinical treatment of pregnancy complications.

Background: Clinical trials have proven that indigo naturalis is a candidate drug for treating ulcerative colitis (UC), but its therapeutic mechanism is still unclear. Purpose: This study aimed to evaluate the protective effect and mechanism of indigo naturalis to treat mice with dextran sulfate sodium (DSS)-induced UC. Methods: DSS-induced UC mice were treated with indigo naturalis (200 mg/kg), indigo (4.76 mg/kg), and indirubin (0.78 mg/kg) for 1 week. The anti-UC mechanism of indigo naturalis was studied by pathological section, inflammatory factor, western blot, and 16S rRNA sequencing. Results: According to body weight change, disease activity index, and colon length, indigo naturalis had the strongest anti DSS-induced UC effect, followed by indirubin and indigo. Pathological section showed that indigo naturalis, indigo, and indirubin could reduce the infiltration of inflammatory cells, increase the secretion of intestinal mucus, and repair the intestinal mucosa. Indigo naturalis, indigo, and indirubin could reduce IL-1β,IL-6, and TNF-α by inhibiting TLR4/MyD88/NF-κB signal transduction. Indigo naturalis and indigo could also reduce IgA and IgG both in serum and colon tissue. In addition, indigo naturalis, indigo, and indirubin could adjust the gut microbiota structure of DSS-induced UC mice, reducing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of probiotics. Conclusion: Indigo and indirubin are one of the main anti-UC components of indigo naturalis. INN could regulate intestinal flora, reduce inflammation, repair intestinal mucosa, and improve the physiological status of DSS-induced UC mice and its anti-UC mechanism may be involved in inhibiting TLR4/MyD88/NF-κB signal transduction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Ma, Zhang, Lin, Han, He and Xie.)

Traditional Chinese medicine( TCM) processing is a traditional pharmaceutical technology unique to China,which is an important means to ensure the safety and effectiveness of clinical medication. As China&apos; s intangible cultural heritage,it contains a wealth of wisdom. With the evolution and optimization of processing methods,Indigo Naturalis,an ancient dye,has gradually become an effective medicine for the treatment of high fever in children,colitis,psoriasis,and leukemia. However,the quality of Indigo Naturalis pieces is difficult to be fundamentally improved due to the unique traditional processing method,complex technology,unclear principle,and outdated equipment. After spending 20 years in exploring the inheritance,innovation,and transformation of ancient lawtheory-principle-technology-equipment-quality control in Indigo Naturalis processing,our research group has basically expounded the processing principle and realized the modern expression and industrial transformation of traditional technology. As China enters a new era,the TCM industry has begun to undergo the high-quality transformation. It is urgent to carry out new excavations and improve the processing,quality,and clinical application of Indigo Naturalis pieces,to better inherit and innovate traditional processing technologies and meet people&apos;s demand for high-quality TCM health services.

Polyethylene glycol (PEG) surface film-forming method was used to prepare hydrophilic Indigo Naturalis decoction pieces with stable effect.The preparation process of modified Indigo Naturalis was optimized and its microscopic properties,hydrophilicity,antipyretic efficacy,and safety were systematically evaluated.With equilibrium contact angle as assessment index,the influence of modifier type,modifier dosage,dispersant dosage,and co-grinding time on water solubility of Indigo Naturalis was investigated by single factor test.The results showed that the optimal preparation process was as follows.The 6%PEG6000 is dissolved in 10%anhydrous ethanol solution by sonification and then the mixture is ground with Indigo Naturalis for 2 min.The resultant product is dried on a square tray in an oven at 60℃to remove ethanol and thereby the PEG-modified hydrophilic Indigo Naturalis decoction pieces are yielded.The morphological observation under scanning electron microscope (SEM) indicated that the modified Indigo Naturalis had smoother surface than Indigo Naturalis,and energy spectrometer measurement showed that the nitrogen (N),calcium(Ca),oxygen (O),and silicon (Si) on the surface of modified Indigo Naturalis powder were less than those of Indigo Naturalis powder.Modified Indigo Naturalis had the equilibrium contact angle 18.96°smaller,polar component 22.222 m J·m~(-2)more,and nonpolar component 7.277 m J·m~(-2)smaller than the Indigo Naturalis powder.Multiple light scattering technique was employed to evaluate the dispersion in water and the result demonstrated that the transmittance of Indigo Naturalis and modified Indigo Naturalis was about85%and 75%,respectively,suggesting the higher dispersity of modified Indigo Naturalis.The suspension rate of modified Indigo Naturalis in water was determined by reflux treatment.The result showed that 57%of Indigo Naturalis was not wetted after refluxing for1 h,while the modified Indigo Naturalis was all wetted and dispersed into water.The dissolution of indigo and indirubin of modified Indigo Naturalis increased and the process was more stable.Then,rats were randomized into the blank group,model group,acetaminophen group,Indigo Naturalis group,and hydrophilic Indigo Naturalis group.The temperature changes of rats were observed after administration and the concentration of IL-1βand TNF-αin serum and IL-1βand PGE&#95;2in hypothalamus was measured.The results indicated that the temperature of Indigo Naturalis group and hydrophilic Indigo Naturalis group dropped and the IL-1βlevel of the hydrophilic Indigo Naturalis group decreased (P&lt;0.05) as compared with those in the model group.Thus,both Indigo Naturalis and hydrophilic Indigo Naturalis had antipyretic effect,particularly the hydrophilic Indigo Naturalis.The acute toxicity test of hydrophilic Indigo Naturalis verified that it had no toxicity to rats.In this study,the hydrophilic Indigo Naturalis decoction pieces were prepared with the PEG surface film-forming method,and the antipyretic efficacy and safety were evaluated,which expanded the technological means of powder modification for Chinese medicine and provided a method for clinical use of Chinese medicine.

Indigo Naturalis( IN) is mainly composed of 10% organic matter and 90% inorganic matter,with a poor wettability and strong hydrophobicity. Indigo,indirubin and effective ingredients are almost insoluble in water. And how it exerts its effect after oral administration still needs to be revealed. For this reason,this study put forward the hypothesis that &quot; Indigo Naturalis forms a slightly soluble calcium carbonate carrier in a strong acid environment of gastric fluid,and organic substances are solubilized in the bile environment of intestinal fluid&quot;,and then verified the hypothesis. First,the dissolution apparatus was used to simulate the change process of IN in different digestive fluid,and the effects of low-dose and normal bile on the dissolution of inorganic substances and the release of organic substances were compared. After the surface morphology and element changes of IN in different digestive fluid were observed,it was found that bile is the key to promoting the dissolution of organic and inorganic substances in IN. Furthermore,the rat fever model induced by 2,4-dinitrophenol was used to study the antipyretic effect of IN in normal rats and bile duct ligation rats. It was found that the antipyretic effect of IN on normal rats was better than that of bile duct ligation rats. The above results indicated that after oral administration of IN,the calcium carbonate carrier was transformed into a slightly soluble state in acidic gastric fluid,and a small amount of organic matter was released. When IN entered the intestinal fluid mixed with bile,the carrier dissolved in a large amount,and indigo and indirubin were dissolved in a large amount,so as to absorb the blood and exert the effect. This study has a certain significance for guiding clinical application of IN. For patients with insufficient bile secretion( such as bile duct resection),oral administration with IN may not be effective and shall be paid attention.

The soaking and fermentation of Baphicacanthus cusia( Nees),the important intermediate link of Indigo Naturalis processing,facilitates the synthesis of indigo and indirubin precursors and the dissolution of endogenous enzymes and other effective components,while the role of microorganisms in the fermentation is ignored. The present study investigated the changes of microbial community structure in Indigo Naturalis processing based on 16 S amplicon sequencing and bioinformatics. Meanwhile,the contents of indigo,indirubin,isatin,tryptanthrin,indole glycoside,etc. were determined to explore the correlation between the microorganisms and the alterations of the main components. As demonstrated by the results,the microbial diversity decreased gradually with the fermentation,which bottomed out after the addition of lime. Proteobacteria,Bacteroidetes,and Firmicutes were the main dominant communities in the fermentation. The relative abundance of Proteobacteria declined gradually with the prolongation of fermentation time,and to the lowest level after the addition of lime. The relative abundance of Firmicutes increased,and that of Bacteroidetes decreased first and then increased. The contents of effective substances in Indigo Naturalis also showed different variation tendencies. As fermentation went on,indole glycoside decreased gradually; indigo first increased and then decreased; indirubin and isatin first decreased and then increased; tryptanthrin gradually increased. Those changes were presumedly related to the roles of microorganisms in the synthesis of different components. This study preliminarily clarified the important role of microorganisms in the soaking and fermentation and provided a scientific basis for the control of Indigo Naturalis processing and the preparation of high-quality Indigo Naturalis.

The coronavirus disease, 2019 (COVID-19), has spread rapidly around the world and become a major public health problem facing the world. Traditional Chinese medicine (TCM) has been fully committed to treat COVID-19 in China. It improved the clinical symptoms of patients and reduced the mortality rate. In light of the fever was identified as one of leading clinical features of COVID-19, this paper will first analyze the material basis of fever, including pyrogenic cytokines and a variety of the mediators of fever. Then the humoral and neural pathways of fever signal transmission will be described. The scattered evidences about fever recorded in recent years are connected in series. On this basis, the understanding of fever is further deepened from the aspects of pathology and physiology. Finally, combining with the chemical composition and pharmacological action of available TCM, we analyzed the mechanisms of TCMs to play the antipyretic effect through multiple ways. So as to further provide the basis for the research of antipyretic compound preparations of TCMs and explore the potential medicines for the prevention and treatment of COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ma, Liu, Luo, He, Wang, Huang, Han, Yang, Xu and Zhang.)

Objectives: Overt and occult hepatitis B infection (HBI) among mothers and infants were investigated, and the effectiveness of vaccination against HBI was evaluated based on transmission types., Methods: A hospital-based cohort was built with 2,734 mothers and 330 mother-infant pairs. Their demographic data were collected. Serological HBV markers, nested-PCR for HBV genes, viral load detection, and phylogenetic analysis were done., Results: The overall prevalence of HBI among mothers was 12.1% (330/2,734), with 10.4% for the overt type and 1.8% for the occult type. In 330 out of 1,650 (20%) mother-infant pairs, the overall, type-I (from overt mother to overt infant), type-II (from overt mother to occult infant), and type-Ⅲ (from occult mother to occult infant) transmissions were 1.9% (1/54), 5.6% (3/54) and 0.0% (0/7). The refinement of HBI classification improved the estimate of vaccine effectiveness against HBI from 74.4%-80.9% to 94.4%, which was more prominent for type-II. One mother-infant pair with type-II transmission shared nearly identical complete sequences. However, the high rate of lost-to-follow-up could not be ignored., Conclusions: During the transition period, HBV is mainly transmitted from the overt type of HBI mother to infant. Intensive prenatal screening for mothers is vital., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease., Objective: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium., Design, Setting, Participants and Intervention: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m 2 , and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg., Main Outcome Measures: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment., Results: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group., Conclusion: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone., Trial Registration Number: NCT02063100 on ClinicalTrials.gov., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

Measurement of electrical conductivity of conductive thin film deposited on a conductive substrate is important and challenging. An effective conductivity model was constructed for a bilayer structure to extract thin film conductivity from the measured Q-factor of a quasi-optical resonator. As a demonstration, aluminium films with thickness of 100 nm were evaporated on four silicon wafers whose conductivity ranges from ~10 1 to ~10 5 S/m (thus, the proposed method can be verified for a substrate with a wide range of conductivity). Measurement results at ~180 GHz show that average conductivities are 1.66 × 10 7 S/m (which agrees well with direct current measurements) with 6% standard deviation. The proposed method provides a contactless conductivity evaluation method for conductive thin film deposited on conductive substrate which cannot be achieved by the existing microwave resonant method.