Phloretin inhibits transmissible gastroenteritis virus proliferation via multiple mechanisms.

Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus, has caused huge economic losses to the pig industry, with 100% mortality in piglets aged 2 weeks and intestinal injury in pigs of other ages. However, there is still a shortage of safe and effective anti-TGEV drugs in clinics. In this study, phloretin, a naturally occurring dihydrochalcone glycoside, was identified as a potent antagonist of TGEV. Specifically, we found phloretin effectively inhibited TGEV proliferation in PK-15 cells, dose-dependently reducing the expression of TGEV N protein, mRNA, and virus titer. The anti-TGEV activity of phloretin was furthermore refined to target the internalization and replication stages. Moreover, we also found that phloretin could decrease the expression levels of proinflammatory cytokines induced by TGEV infection. In addition, we expanded the potential key targets associated with the anti-TGEV effect of phloretin to AR, CDK2, INS, ESR1, ESR2, EGFR, PGR, PPARG, PRKACA, and MAPK14 with the help of network pharmacology and molecular docking techniques. Furthermore, resistant viruses have been selected by culturing TGEV with increasing concentrations of phloretin. Resistance mutations were reproducibly mapped to the residue (S242) of main protease (Mpro). Molecular docking analysis showed that the mutation (S242F) significantly disrupted phloretin binding to Mpro, suggesting Mpro might be a potent target of phloretin. In summary, our findings indicate that phloretin is a promising drug candidate for combating TGEV, which may be helpful for developing pharmacotherapies for TGEV and other coronavirus infections.

Life cycle assessment of hepatotoxicity induced by cyhalofop-butyl in environmental concentrations on zebrafish in light of gut-liver axis.

Cyhalofop-butyl (CB) poses a significant threat to aquatic organisms, but there is a discrepancy in evidence about hepatotoxicity after prolonged exposure to environmental levels. The aim of this study was to investigate long-term hepatotoxicity and its effects on the gut-liver axis through the exposure of zebrafish to environmental concentrations of CB (0.1,1,10 µg/L) throughout their life cycle. Zebrafish experienced abnormal obesity symptoms and organ index after a prolonged exposure of 120 days. The gut-liver axis was found to be damaged both morphologically and functionally through an analysis of histology, electron microscopy subcellular structure, and liver function. The disruption of the gut-liver axis inflammatory process by CB is suggested by the rise in inflammatory factors and the alteration of inflammatory genes. Furthermore, there was a noticeable alteration in the blood and gut-liver axis biochemical parameters as well as gene expression linked to lipid metabolism, which may led to an imbalance in the gut flora. In conclusion, the connection between the gut-liver axis, intestinal microbiota, and liver leads to the metabolic dysfunction of zebrafish exposed to long-term ambient concentrations of CB, and damaged immune system and liver lipid metabolism. This study gives another knowledge into the hepatotoxicity component of long haul openness to ecological centralization of CB, and might be useful to assess the potential natural and wellbeing dangers of aryloxyphenoxypropionate herbicides.

Regulation of the CB1R/AMPK/PGC-1α signaling pathway in mitochondria of mouse hearts and cardiomyocytes with chronic intermittent hypoxia.

PURPOSE: This study evaluated the effects of chronic intermittent hypoxia (CIH) at different times on the mitochondria of mouse hearts and H9C2 cardiomyocytes to determine the role of the cannabinoid receptor 1 (CB1R)/adenosine 5'-monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) signaling pathway. METHODS: Animal and cellular CIH models were prepared in an intermittent hypoxia chamber at different times. The cardiac function of mice was determined, and heart tissue and ultrastructural changes were observed. Apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential were detected, and MitoTracker™ staining was performed to observe cardiomyocyte mitochondria. Western blot, immunohistochemistry, and cellular immunofluorescence were also performed. RESULTS: In the short-term CIH group, increases in mouse ejection fraction (EF) and heart rate (HR); mitochondrial division; ROS and mitochondrial membrane potential; and the expression levels of CB1R, AMPK, and PGC-1α were observed in vivo and in vitro. In the long-term CIH group, the EF and HR increased, the myocardial injury and mitochondrial damage were more severe, mitochondrial synthesis decreased, the apoptosis percentage and ROS increased, mitochondrial fragmentation increased, membrane potential decreased, CB1R expression increased, and AMPK and PGC-1α expression levels decreased. Targeted blocking of CB1R can increase AMPK and PGC-1α, reduce damage attributed to long-term CIH in mouse hearts and H9C2 cells, and promote mitochondrial synthesis. CONCLUSION: Short-term CIH can directly activate the AMPK/PGC-1α pathway, promote mitochondrial synthesis in cardiomyocytes, and protect cardiac structure and function. Long-term CIH can increase CB1R expression and inhibit the AMPK/PGC-1α pathway, resulting in structural damage, the disturbance of myocardial mitochondria synthesis, and further alterations in the cardiac structure. After targeted blocking of CB1R, levels of AMPK and PGC-1α increased, alleviating damage to the heart and cardiomyocytes caused by long-term CIH.

A cross-sectional study of the endorsement proportion of reporting guidelines in 1039 Chinese medical journals.

BACKGROUND: Reporting quality is a critical issue in health sciences. Adopting the reporting guidelines has been approved to be an effective way of enhancing the reporting quality and transparency of clinical research. In 2012, we found that only 7 (7/1221, 0.6%) journals adopted the Consolidated Standards of Reporting Trials (CONSORT) statement in China. The aim of the study was to know the implementation status of CONSORT and other reporting guidelines about clinical studies in China. METHODS: A cross-sectional bibliometric study was conducted. Eight medical databases were systematically searched, and 1039 medical journals published in mainland China, Hong Kong, Macau, and Taiwan were included. The basic characteristics, including subject, language, publication place, journal-indexed databases, and journal impact factors were extracted. The endorsement of reporting guidelines was assessed by a modified 5-level evaluation tool, namely i) positive active, ii) positive weak, iii) passive moderate, iv) passive weak and v) none. RESULTS: Among included journals, 24.1% endorsed CONSORT, and 0.8% endorsed CONSORT extensions. For STROBE (STrengthening the Reporting of Observational Studies in Epidemiology), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), STARD (An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies), CARE (CAse REport guidelines), the endorsement proportion were 17.2, 16.6, 16.4, and 14.8% respectively. The endorsement proportion for SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials), TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis), AGREE (Appraisal of Guidelines, Research, and Evaluation), and RIGHT (Reporting Items for Practice Guidelines in Healthcare) were below 0.7%. CONCLUSIONS: Our results showed that the implementation of reporting guidelines was low. We suggest the following initiatives including i) enhancing the level of journal endorsement for reporting guidelines; ii) strengthening the collaboration among authors, reviewers, editors, and other stakeholders; iii) providing training courses for stakeholders; iv) establishing bases for reporting guidelines network in China; v) adopting the endorsement of reporting guidelines in the policies of the China Periodicals Association (CPA); vi) promoting Chinese medical journals into the international evaluation system and publish in English.

Association of Radical Chemistry with LanD Flavoprotein Activity for C-Terminal Macrocyclization of a Ribosomal Peptide by Formation of an Unsaturated Thioether Residue.

LanD flavoproteins catalyze oxidative decarboxylation of the C-terminal Cys residue of a peptide to produce an enethiol. This enethiol is highly reactive and can be coupled with an upstream dehydroamino acid through Michael addition to form S-[2-aminovinyl](3-methyl)cysteine, an unsaturated thioether residue known to be characteristic of an array of C-terminally macrocyclized, ribosomally synthesized and posttranslationally modified peptides (RiPPs). Based on a two-stage bioinformatics mining of posttranslational modifications (PTMs) related to C-terminal Cys processing, we report herein that LanD activity can couple with radical S-adenosylmethionine chemistry to provide a new unsaturated thioether residue, S-[2-aminovinyl]-3-carbamoylcysteine, by conjugating the resultant enethiol with Cß of the Asn residue in the C-terminal NxxC motif of a peptide for macrocyclization. This study furthers our understanding of the variety of PTMs involved in creating the structure diversity of macrocyclic RiPPs.

SAF-248, a novel PI3Kδ-selective inhibitor, potently suppresses the growth of diffuse large B-cell lymphoma.

PI3Kδ is expressed predominately in leukocytes and overexpressed in B-cell-related malignances. PI3Kδ has been validated as a promising target for cancer therapy, and specific PI3Kδ inhibitors were approved for clinical practice. However, the substantial toxicity and relatively low efficacy as a monotherapy in diffuse large B-cell lymphoma (DLBCL) limit their clinical use. In this study, we described a novel PI3Kδ inhibitor SAF-248, which exhibited high selectivity for PI3Kδ (IC50 = 30.6 nM) over other PI3K isoforms at both molecular and cellular levels, while sparing most of the other human protein kinases in the kinome profiling. SAF-248 exhibited superior antiproliferative activity against 27 human lymphoma and leukemia cell lines compared with the approved PI3Kδ inhibitor idelalisib. In particular, SAF-248 potently inhibited the proliferation of a panel of seven DLBCL cell lines (with GI50 values < 1 µM in 5 DLBCL cell lines). We demonstrated that SAF-248 concentration-dependently blocked PI3K signaling followed by inducing G1 phase arrest and apoptosis in DLBCL KARPAS-422, Pfeiffer and TMD8 cells. Its activity against the DLBCL cells was negatively correlated to the protein level of PI3Kα. Oral administration of SAF-248 dose-dependently inhibited the growth of xenografts derived from Pfeiffer and TMD8 cells. Activation of mTORC1, MYC and JAK/STAT signaling was observed upon prolonged treatment and co-targeting these pathways would potentiate the activity of SAF-248. Taken together, SAF-248 is a promising selective PI3Kδ inhibitor for the treatment of DLBCL and rational drug combination would further improve its efficacy.

Molecular cloning and tissue distribution of the leptin gene in gibel carp (Carassius auratus gibelio): Regulation by postprandial and long-term fasting treatment.

Leptin is a multifunctional hormone that serves as a feeding regulator in mammals. However, the effect of leptin on fish remains unclear. We sequenced the leptin gene from gibel carp (Carassius auratus gibelio) and designated it gLEP. The length of the gLEP cDNA sequence was 562 bp, including an open reading frame (ORF) of 516 bp. The ORF putatively encodes a peptide of 171 amino acids, including a signal peptide of 20 amino acids. gLEP shared low primary amino acid sequence homology with leptin genes in vertebrates, whereas three-dimensional (3D) structural modeling revealed strong identity with the structures in other vertebrates. gLEP mRNA was widely distributed in all of the tissue that we examined, with the highest levels of expression in the hepatopancreas. Hepatopancreas gLEP mRNA expression levels showed no changes following postprandial treatment. However, hepatopancreas gLEP mRNA expression levels greatly decreased (P < 0.05) after fasting but substantially increased (P < 0.05) after refeeding in the long-term fasting treatment. In summary, these results indicate that leptin expression could be influenced by the regulation of food intake. These results provide the initial step toward elucidating the appetite regulatory systems associated with leptin in gibel carp.

Study on Controllable Assembly of Stearic Acid within Interlayer Spacing of Montmorillonite and Its Energy Storage Performance.

As an energy carrier, the phase change material can enhance the efficiency of an energy source and reduce its load. The present paper describes the assembly of the energy carrier molecule [stearic acid (SA)] into the interlayer spacing of montmorillonite (Mt). A novel inorganic/organic composite energy storage material was prepared, which effectively reduces the phase change temperature of the energy storage molecule. Through acid treatment, the Si4+/Al3+ ratio of Mt can be regulated to obtain a series of Mts with different layer charges. As a result, a controllable assembly of energy storage molecule, SA, into the interlayer spacing of Mts with different layer charges was accomplished. By controlling the layer charges of Mt arrangement morphology and interactive force of SA molecules in the interlayer, spacing of Mt can be changed effectively. The phase change temperature (exothermic reaction) reduces from 50.5 to 32 °C compared with the SA molecules, which are used to control phase change temperature of the energy storage material. The study presents a SA/Mt energy storage material that can aid in further development in the field of energy storage construction materials.

Nonpharmacological Interventions for Cancer-Related Fatigue: A Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND: Nonpharmacological interventions are the first recommendation for cancer-related fatigue, according to current guidelines. There are many forms of nonpharmacological interventions for addressing cancer-related fatigue, but the preferred means remain controversial and are not stated in the guidelines. Therefore, we evaluated the comparative effects and ranks of all major nonpharmacological interventions, according to different assessment methods, in cancer patients with fatigue. METHODS: Medline, Embase, Cochrane Library, and Allied and Complementary Medicine Database were searched for randomized controlled trials on nonpharmacological treatments for cancer-related fatigue. We assessed the trials' methodological quality using the Cochrane Risk of Bias tool. A Bayesian network meta-analysis and a comparative effects ranking were performed with Aggregate Data Drug Information System software. RESULTS: A total of 16,675 items were obtained from the databases, and 182 studies comprising 18,491 participants were included in the analysis. Based on the ranking probabilities, multimodal therapy and qigong ranked best with a Brief Fatigue Inventory; for a Functional Assessment of Cancer Therapy-fatigue scale, combined psychosocial therapies and bright white light therapy ranked best; for the Piper Fatigue Scale, resistance exercise and mindfulness-based stress reduction ranked best; for a multidimensional fatigue inventory, multimodal therapy and cognitive behavioral therapy (CBT) ranked best; for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), acupuncture and CBT ranked best; and for the Profile of Mood States Fatigue Subscale, multimodal therapy, qigong, aerobic exercise, and CBT ranked best. Comprehensive analysis of the results indicated that multimodal therapy, CBT, and qigong might be the optimum selections for reducing cancer-related fatigue. Most of the included studies had low risk of methodological quality problems; however, 59 studies had low methodological quality. LINKING EVIDENCE TO ACTION: Different interventions have their own sets of advantages for addressing cancer-related fatigue. These results can be utilized as evidence-based interventions for healthcare workers and patients to manage cancer-related fatigue.

Psychosocial interventions for Alzheimer's disease cognitive symptoms: a Bayesian network meta-analysis.

BACKGROUND: Alzheimer disease (AD) is the most common type of dementia with cognitive decline as one of the core symptoms in older adults. Numerous studies have suggested the value of psychosocial interventions to improve cognition in this population, but which one should be preferred are still matters of controversy. Consequently, we aim to compare and rank different psychosocial interventions in the management of mild to moderate AD with cognitive symptoms. METHODS: We did a network meta-analysis to identify both direct and indirect evidence in relevant studies. We searched MEDLINE, EMBASE, PsycINFO through the OVID database, CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating psychosocial interventions of cognitive symptoms in patients with Alzheimer disease, published up to August 31, 2017. We included trials of home-based exercise(HE), group exercise(GE), walking program(WP), reminiscence therapy(RT), art therapy(AT) or the combination of psychosocial interventions and acetylcholinesterase inhibitor (ChEIs). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. The outcomes investigated were Mini-Mental State Examination (MMSE) and compliance. We did a pair-wise meta-analysis using the fixed-effects model and then did a random-effects network meta-analysis within a Bayesian framework. RESULTS: We deemed 10 trials eligible, including 682 patients and 11 treatments. The quality of included study was rated as low in most comparison with Cochrane tools. Treatment effects from the network meta-analysis showed WP was better than control (SMD 4.89, 95% CI -0.07 to 10.00) while cognitive training and acetylcholinesterase inhibitor (CT + ChEIs) was significantly better than the other treatments, when compared with simple ChEIs treatment, assessed by MMSE. In terms of compliance, the pair-wise meta-analysis indicated that WP and HE are better than GE and AT, while CT + ChEIs, CST + ChEIs are better than other combined interventions. CONCLUSION: Our study confirmed the effectiveness of psychosocial interventions for improving cognition or slowing down the progression of cognitive impairment in AD patients and recommended several interventions for clinical practice.

Enzymatic Formation of an Aminovinyl Cysteine Residue in Ribosomal Peptide Natural Products.

The carboxyl-terminal (C-terminal) S-[(Z)-2-aminovinyl]-cysteine (AviCys) analogs have been identified in four families of ribosomally synthesized and post-translationally modified peptides (RiPPs): lanthipeptides, linaridins, thioamitides, and lipolanthines. Within identified biosynthetic pathways, a highly reactive enethiol intermediate, formed through an oxidative decarboxylation catalyzed by a LanD-like flavoprotein, can undergo two types of cyclization: a Michael addition with a dehydroamino acid or a coupling reaction initiated by a radical species. The collaborative actions of LanD-like proteins with diverse enzymes involved in dehydration, dethiolation or cyclization lead to the construction of structurally distinct peptide natural products with analogous C-terminal macrocyclic moieties. This concept summarizes existing knowledge regarding biosynthetic pathways of AviCys analogs to emphasize the diversity of biosynthetic mechanisms that paves the way for future genome mining explorations into diverse peptide natural products.

Detection of Hepatocellular Carcinoma in an Orthotopic Patient-Derived Xenograft with an Epithelial Cell Adhesion Molecule-Specific Peptide.

Hepatocellular carcinoma (HCC) has emerged as a major contributor to the worldwide cancer burden. Improved methods are needed for early cancer detection and image-guided surgery. Peptides have small dimensions that can overcome delivery challenges to achieve high tumor concentrations and deep penetration. We used phage display methods to biopan against the extra-cellular domain of the purified EpCAM protein, and used IRDye800 as a near-infrared (NIR) fluorophore. The 12-mer sequence HPDMFTRTHSHN was identified, and specific binding to EpCAM was validated with HCC cells in vitro. A binding affinity of kd = 67 nM and onset of k = 0.136 min-1 (7.35 min) were determined. Serum stability was measured with a half-life of T1/2 = 2.6 h. NIR fluorescence images showed peak uptake in vivo by human HCC patient-derived xenograft (PDX) tumors at 1.5 h post-injection. Also, the peptide was able to bind to foci of local and distant metastases in liver and lung. Peptide biodistribution showed high uptake in tumor versus other organs. No signs of acute toxicity were detected during animal necropsy. Immunofluorescence staining of human liver showed specific binding to HCC compared with cirrhosis, adenoma, and normal specimens.

Screening of Poria cocos polysaccharide with immunomodulatory activity and its activation effects on TLR4/MD2/NF-κB pathway.

PCP-W1, the Poria cocos polysaccharide with the strong immunomodulatory activity, was isolated through column chromatography and screened for in vitro immune activity in RAW 264.7 cells in this study. The structure analysis results revealed that the PCP-W1 were composed of galactose, glucose, fucose and mannose in a molar percentage of 35.87: 28.56: 21.77: 13.64. And it exhibited a random coil and branched conformational features with a molecular weight of 18.38 kDa. The main chain consisted of residues→3)-ß-D-Glcp-(1 â†’ 3,6)-ß-D-Glcp-(1 â†’ 3)-ß-D-Glcp-(1 â†’ 6)-ß-D-Glcp-(1 â†’ 6)-α-D-Galp-(1 â†’ 6)-α-D-Galp-(1 â†’ 2,6)-α-D-Galp-(1→6)-α-D-Galp-(1 â†’ 6)-α-D-Galp-(1 â†’ , while branching occurred at ß-D-Glcp-(1→, α-D-Manp-(1→, and α-L-Fucp-(1 â†’ 3)- α-L-Fucp-(1→. The pharmacodynamic studies demonstrated that PCP-W1 activated the release of NO, IL-6, IL-ß, TNF-α, CD86, and ROS to induce polarization of RAW 264.7 murine macrophages towards M1-type through modulation of the TLR4/MD2/NF-κB pathway. The molecular docking results showed that PCP-W1 could primarily dock onto the hydrophobic binding site of TLR4/MD2 complex via its galactose chain. Furthermore, molecular dynamics simulation displayed stable modeling for TLR4-MD2-PCP-W1 complex. Overall, we screened the most immunoactive components of the polysaccharide, analyzed its structure, demonstrated its impact on TLR4/MD2/NF-kB pathway, and studied the interaction between TLR4/MD2 and the polysaccharide fragments. These results provide further support for the structure-activity relationship study of the immunomodulatory effects of Poria cocos polysaccharide.

Exploration of registration and the risk of bias in acupuncture randomised controlled trials: a systematic review protocol.

BACKGROUND: Randomised controlled trials (RCTs) are the predominant type in acupuncture clinical research, and the publications have increased rapidly in recent years, but there is a prevalence of the high risk of bias and poor methodological design in acupuncture RCTs. Clinical trial registration can improve the transparency and credibility of studies by disclosing key information in advance. However, the registration in acupuncture RCTs is not satisfactory, as there is widespread of the under-registration, inconsistency with published studies and insufficient disclosure of key methodological information. Whether registration can reduce the risk of bias in acupuncture RCTs and improve data transparency has not been fully explored. Therefore, we constructed this study to investigate the association between registration and risk of bias and data sharing level in acupuncture RCTs. METHODS: Seven databases including MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang and VIP databases will be systematically searched between 1 January 2014 and 31 March 2024, for acupuncture RCTs. Two reviewers will independently extract data using a predefined standardised format and perform secondary validation. The characteristics and data sharing level of the included studies will be summarised. The risk of bias of included RCTs will be assessed by the revised Cochrane risk-of-bias tool for randomised trials. The risk of bias and registration in acupuncture RCTs will be analysed by logistic or quantile regression analyses (depending on the number of minimum events). The data sharing level and registration will be analysed by quantile regression analyses. ETHICS AND DISSEMINATION: As the systematic review aims to consolidate info from published sources, ethical approval is not necessary for this study. The study's findings will be submitted to a peer-reviewed academic journal and disseminated via conference presentations. This protocol has been registered in Open Science Framework Registries.

Reporting and influencing factors of patient-reported outcomes in acupuncture randomised controlled trials: a cross-sectional study protocol.

INTRODUCTION: Patient-reported outcomes (PROs) are health reports that come directly from the patients themselves and represented the experience and insights of the patient's perspective on the impact of the intervention. PROs were increasingly emphasised in acupuncture randomised controlled trials (RCTs). However, the reporting quality of PROs in acupuncture RCTs has not been investigated to date. Therefore, we constructed this study to reveal the basic characteristics and reporting quality of PROs in acupuncture RCTs, and explore the relationship between concealment, blinding and RROs. We hope our findings can provide guidance for the reporting standards and future development of PROs in acupuncture RCTs in reverse. METHODS AND ANALYSIS: RCTs using acupuncture treatment as the intervention and PROs as primary outcomes or secondary outcomes will be systematically searched through seven databases MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang and VIP between 1 January 2012 and 15 October 2022. The basic characteristics, concealment, blinding design and the characteristics of PROs in included RCTs will be summarised. The reporting quality of PROs will be assessed based on the CONSORT PRO extension. Logistic analysis will be performed to identify the association between concealment, blinding and RROs. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. This protocol has been registered in Open Science Framework (OSF) Registries. The findings of this study will be submitted to a peer-reviewed academic journal.

Chromosome-level genome assembly and population genomic analysis provide insights into the genetic diversity and adaption of Schizopygopsis younghusbandi on the Tibetan Plateau.

The Yarlung Tsangpo River on the Tibetan Plateau provides a unique natural environment for studying fish evolution and ecology. However, the genomes and genetic diversity of plateau fish species have been rarely reported. Schizopygopsis younghusbandi, a highly specialized Schizothoracine species and economically important fish inhabiting the Yarlung Tsangpo River, is threatened by overfishing and biological invasion. Herein, we generated a chromosome-level genome of S. younghusbandi and whole-genome resequencing data for 59 individuals from six locations of the river. The results showed that the divergence time between S. younghusbandi and other primitive Schizothoracine species was ∼4.2 Mya, coinciding with the major phase of the Neogene Tibetan uplift. The expanded gene families enriched in DNA integration and replication, ion binding and transport, energy storage, and metabolism likely contribute to the adaption of this species. The S. younghusbandi may have diverged from other highly specialized Schizothoracine species in the Zanda basin during the Pliocene epoch, which underwent major population reduction possibly due to the drastic climate change during the last glacial period. Population analysis indicated that the ancient population might have originated upstream before gradually adapting to evolve into the populations inhabiting the mid-stream and downstream regions of the Yarlung Tsangpo River. In conclusion, the chromosome-level genome and population diversity of S. younghusbandi provide valuable genetic resources for the evolution, ecology, and conservation studies of endemic fishes on the Tibetan Plateau.

An individualized immune prognostic signature in nasopharyngeal carcinoma.

BACKGROUND: Immune-related characteristics can serve as reliable prognostic biomarkers in various cancers. Herein, we aimed to construct an individualized immune prognostic signature in nasopharyngeal carcinoma (NPC). METHODS: This study retrospectively included 455 NPC samples and 39 normal healthy nasopharyngeal tissue specimens. Samples from Gene Expression Omnibus (GEO) were obtained as discovery cohort to screen candidate prognostic immune-related gene pairs based on relative expression ordering of the genes. Quantitative real-time reverse transcription-PCR was used to detect the selected genes to construct an immune-related gene pair signature in training cohort, which comprised 118 clinical samples, and was then validated in validation cohort 1, comprising 92 clinical samples, and validation cohort 2, comprising 88 samples from GEO. RESULTS: We identified 26 immune-related gene pairs as prognostic candidates in discovery cohort. A prognostic immune signature comprising 11 immune gene pairs was constructed in training cohort. In validation cohort 1, the immune signature could significantly distinguish patients with high or low risk in terms of progression-free survival (PFS) (hazard ratio [HR] 2.66, 95 % confidence interval (CI) 1.17-6.02, P=0.015) and could serve as an independent prognostic factor for PFS in multivariate analysis (HR 2.66, 95 % CI 1.17-6.02, P=0.019). Similar results were obtained using validation cohort 2, in which PFS was significantly worse in high risk group than in low risk group (HR 3.02, 95 % CI 1.12-8.18, P=0.022). CONCLUSIONS: The constructed immune signature showed promise for estimating prognosis in NPC. It has potential for translation into clinical practice after prospective validation.

Progress in the study of aging marker criteria in human populations.

The use of human aging markers, which are physiological, biochemical and molecular indicators of structural or functional degeneration associated with aging, is the fundamental basis of individualized aging assessments. Identifying methods for selecting markers has become a primary and vital aspect of aging research. However, there is no clear consensus or uniform principle on the criteria for screening aging markers. Therefore, we combine previous research from our center and summarize the criteria for screening aging markers in previous population studies, which are discussed in three aspects: functional perspective, operational implementation perspective and methodological perspective. Finally, an evaluation framework has been established, and the criteria are categorized into three levels based on their importance, which can help assess the extent to which a candidate biomarker may be feasible, valid, and useful for a specific use context.

Comparing the Performance of Two Screening Questionnaires for Chronic Obstructive Pulmonary Disease in the Chinese General Population.

Purpose: Screening questionnaires can help identify individuals at a high risk of COPD. This study aimed to compare the performance of the COPD population screener (COPD-PS) and COPD screening questionnaire (COPD-SQ) on the general population as a full cohort and stratified by urbanization. Methods: We recruited subjects who underwent a health checkup at urban and rural community health centers in Beijing. All eligible subjects completed the COPD-PS and COPD-SQ, then spirometry. Spirometry-defined COPD was defined as a post-bronchodilator FEV1/FVC<70%. Symptomatic COPD was defined as a post-bronchodilator FEV1/FVC<70% and respiratory symptoms. Receiver operating characteristic (ROC) curve analysis compared the discriminatory power of the two questionnaires, and stratified by urbanization. Results: We identified 129 spirometry-defined and 92 symptomatic COPD cases out of 1350 enrolled subjects. The optimal cut-off score for the COPD-PS was 4 for spirometry-defined and 5 for symptomatic COPD. The optimum cut-off score for the COPD-SQ was 15 for both spirometry-defined and symptomatic COPD. The COPD-PS and COPD-SQ had similar AUC values for spirometry-defined (0.672 vs 0.702) and symptomatic COPD (0.734 vs 0.779). The AUC of the COPD-SQ tended to be higher in rural areas than that of the COPD-PS for spirometry-defined COPD (0.700 vs 0.653, P = 0.093). Conclusion: The COPD-PS and COPD-SQ had comparable discriminatory power for detecting COPD in the general population while the COPD-SQ performed better in rural areas. A pilot study for validating and comparing the diagnostic accuracy of different questionnaires is required when screening for COPD in a new environment.

Reporting and data-sharing level of acupuncture randomised controlled trials: a cross-sectional study protocol.

INTRODUCTION: Randomised controlled trials (RCTs) play an important role in evidence-based medicine. However, an article with low reporting quality may mislead both experts and the general public into an erroneous decision. Data sharing can contribute to the truthfulness and transparency of trials. Acupuncture RCTs have been increasing rapidly these years, but the reporting quality and data-sharing level of acupuncture RCTs are not clear. Thus, this study will provide the current status of the reporting quality and data-sharing level of acupuncture RCTs. METHODS AND ANALYSIS: A cross-sectional study will be conducted. The seven databases including MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang Database and VIP will be searched between 1 January 2012 and 15 October 2022 to identify acupuncture RCTs. The basic characteristics of included trials will be summarised. The reporting quality for included RCTs will be assessed by the Consolidated Standards for Reporting Trials 2010 statement and the Standards for Reporting Interventions in Controlled Trials of Acupuncture. The data-sharing level will be assessed by open science practices. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. This protocol has been registered in Open Science Framework Registries. The findings of this study will be submitted to a peer-reviewed academic journal.