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Writing is a challenging task for students in language learning. A key question in this challenge is how to exploit the potential of information technology and design effective learning strategies to promote quality writing. This is a question that Chinese teachers need to actively consider in the process of optimizing their writing instruction. Therefore, this study embedded problem-based scaffolds in an SVVR system and proposed a second-order progressive problem-based scaffold (SPPS-SVVR) strategy to enhance students' writing skills. To examine the effectiveness of the proposed strategy, a quasi-experiment was conducted in an elementary school in China. The experimental group (39 students) used the SPPS-SVVR writing strategy, while the control group (39 students) used the traditional SVVR writing strategy (T-SVVR). The study results showed that the SPPS-SVVR writing strategy not only significantly improved the students' writing performance, but also increased their learning engagement and transferability. In addition, the results of epistemic network structure analysis showed that students using the SPPS-SVVR writing strategy focused on writing in terms of internal, mental, and dynamic environments. Interviews revealed that the SPPS-SVVR writing strategy supported the experimental group students' grasp of writing ideas and verbal expressions, and they were more satisfied with this strategy.

Abstract Background The effectiveness and safety of acupuncture therapy to delay lung function decline in chronic obstructive pulmonary disease (COPD) remain unclear. This study aimed to determine whether acupuncture, as an adjunctive therapy to COPD-guided medication, could prevent lung function decline. Methods This randomised, two-centre study was conducted between February 2022 and July 2023. Men and women aged 40–80 years with COPD were recruited. Participants received active or sham acupuncture three times a week (36 sessions total). The primary outcome was the change in the percentage of forced expiratory volume for 1 s to the predicted value (FEV1%) between the baseline and after the intervention. Results Overall, 238 participants were screened, and 74 (58 men [78.4%]; mean [standard deviation] age, 69.6 [7.2] years) were randomised into the acupuncture and sham acupuncture groups (37 per group). After the intervention, the change in FEV1% was 1.35 (95% confidence interval [CI]: -0.47 to 3.17) and -2.44 (95% CI: -4.56 to -0.33) in the acupuncture and sham acupuncture groups, respectively. The difference was -3.97 (95% CI: -6.2 to -1.74), and the adjusted difference was -3.46 (95% CI: -5.69 to -1.24, P = 0.003) between the groups. A significantly less decline was found in forced expiratory volume for 1 s in the acupuncture group. All treatment-related adverse events (acupuncture = 11, sham = 2) were mild. Conclusions Compared with sham acupuncture, acupuncture plus medication may delay lung function decline. However, further studies with a larger sample size and longer-term follow-up are needed to clarify the effects.

Abstract Background Gastric cancer (GC) is one of the most common cancers worldwide. Tumor microenvironment plays an important role in tumor progression. This study aims to explore the role of cancer-associated fibroblasts (CAFs) in GC and the underlying mechanism. Methods Cell viability, proliferation, invasion and migration were assessed by MTT, EdU, transwell and wound healing assays, respectively. Sphere formation assay was used to evaluate cell stemness. Glucose consumption, lactate production and ATP consumption were measured to assess glycolysis. In addition, The RNA and protein expression were detected by qRT-PCR and western blot. The interaction between wingless Type MMTV Integration Site Family, Member 5 A (WNT5A) and hexokinase 2 (HK2) was verified by Co-immunoprecipitation. The xenograft model was established to explore the function of CAFs on GC tumor growth in vivo. Results CAFs promoted the proliferation, metastasis, stemness and glycolysis of GC cells. WNT5A was upregulated in CAFs, and CAFs enhanced WNT5A expression in GC cells. Knockdown of WNT5A in either GC cells or CAFs repressed the progression of GC cells. In addition, WNT5A promoted HK2 expression, and overexpression of HK2 reversed the effect of WNT5A knockdown in CAFs on GC cells. Besides, knockdown of WNT5A in CAFs inhibits tumor growth in vivo. Conclusion CAF-derived WNT5A facilitates the progression of GC via regulating HK2 expression.

Introduction: Reverse genetic studies conducted in the plant with a complex or polyploidy genome enriched with large gene families (like wheat) often meet challenges in identifying the key candidate genes related to important traits and prioritizing the genes for functional experiments. Objective: To overcome the above-mentioned challenges of reverse genetics, this work aims to establish an efficient multi-species strategy for genome-wide gene identification and prioritization of the key candidate genes. Methods: We established the integrative gene duplication and genome-wide analysis (iGG analysis) as a strategy for pinpointing key candidate genes deserving functional research. The iGG captures the evolution, and the expansion/contraction of large gene families across phylogeny-related species and integrates spatial–temporal expression information for gene function inference. Transgenic approaches were also employed to functional validation. Results: As a proof-of-concept for the iGG analysis, we took the wheat calcineurin B-like protein-interacting protein kinases (CIPKs) family as an example. We identified CIPKs from seven monocot species, established the orthologous relationship of CIPKs between rice and wheat, and characterized Triticeae-specific CIPK duplicates (e.g., CIPK4 and CIPK17). Integrated with our analysis of CBLs and CBL-CIPK interaction, we revealed that divergent expressions of TaCBLs and TaCIPKs could play an important role in keeping the stoichiometric balance of CBL-CIPK. Furthermore, we validated the function of TaCIPK17-A2 in the regulation of drought tolerance by using transgenic approaches. Overexpression of TaCIPK17 enhanced antioxidant capacity and improved drought tolerance in wheat. Conclusion: The iGG analysis leverages evolutionary and comparative genomics of crops with large genomes to rapidly highlight the duplicated genes potentially associated with speciation, domestication and/or particular traits that deserve reverse-genetic functional studies. Through the identification of Triticeae-specific TaCIPK17 duplicates and functional validation, we demonstrated the effectiveness of the iGG analysis and provided a new target gene for improving drought tolerance in wheat.

Background: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration. Methods: The population-based sample of adults in Guangzhou, China (baseline: 40–83 years old; n = 5,118) was followed up about every 3 years. All are tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-day real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome. Results: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5,118 participants aged 40–83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3,628 (71%) completed at least one on-site follow-up, with a median duration of 9.48 years. Conclusion: The cohort will provide data that will be influential in establishing the role of nutrition in metabolic diseases with multi-omics.

Drug treatment studies are a focal point for identifying novel approaches to reduce myopia progression through basic science research. Here, we investigated the effects of various brimonidine administration routes and concentrations on form-deprivation myopia (FDM) progression, matrix metalloproteinase-2 (MMP-2), and collagen alpha1 chain of type I (COL1A1) expression in the retinal pigment epithelial (RPE)-choroid complex and sclera of guinea pigs. They demonstrate that brimonidine has the capacity to impede choroidal thinning induced by FDM, potentially through the induction of choroidal vasodilation. Additionally, we observed that brimonidine effectively counteracts FDM-induced downregulation of choroidal and scleral MMP-2 expression. Suppression of MMP-2 expression may reduce disruption of scleral and choroidal structural integrity which reduces declines in choroidal blood circulation and mitigates increases in ocular elongation. This research elucidates the effects of brimonidine on myopia progression, offering potential insights into therapeutic interventions for myopia.

Abstract In gravitational collapses, the horizon and singularity’s realisation in the finite future of the proper time used co-moving observer happens in the future of infinitely far away future of the normal time used outside probe. To the latter the horizon and singularity defined in the singularity theorem are physical realities only in the sense of uncertainty principle and ensemble interpretation. We provide two exact time dependent solution families to the Einstein equation and show that they form a pair of complementary description for the microscopic state of black holes by showing that the Bekenstein–Hawking entropy formula follows properly from their canonical wave function’s degeneracy. We also develop an eXact One Body method for general relativity two-body dynamics whose conservative part calls no post newtonian approximation as input and applies to the full three stages of black hole binary merger events. By this method, we analytically calculate the gravitational wave forms following from such merger processes. In the case black holes carry exact and apriori horizon and singularity our wave forms agree with those following from conventional effective one body method but exhibit more consistent late time behaviour. In the case black holes carry only asymptotic horizon and extended inner structure thus experiencing banana shape deformation as the merger occurs, our wave forms exhibit all features especially the late time quasi-normal mode type oscillation seen in real observations.

Abstract Background Patients with spondyloarthritis (SpA)/HLA-B27-associated acute anterior uveitis (AAU) experience recurring acute flares, which pose significant visual and financial challenges. Despite established links between SpA and HLA-B27-associated AAU, the exact mechanism involved remains unclear, and further understanding is needed for effective prevention and treatment. Methods To investigate the acute pathogenesis of SpA/HLA-B27-associated AAU, Mendelian randomization (MR) and single-cell transcriptomic analyses were employed. The MR incorporated publicly available protein quantitative trait locus data from previous studies, along with genome-wide association study data from public databases. Causal relationships between plasma proteins and anterior uveitis were assessed using two-sample MR. Additionally, colocalization analysis was performed using Bayesian colocalization. Single-cell transcriptome analysis utilized the anterior uveitis dataset from the Gene Expression Omnibus (GEO) database. Dimensionality reduction, clustering, transcription factor analysis, pseudotime analysis, and cell communication analysis were subsequently conducted to explore the underlying mechanisms involved. Results Mendelian randomization analysis revealed that circulating levels of AIF1 and VARS were significantly associated with a reduced risk of developing SpA/HLA-B27-associated AAU, with AIF1 showing a robust correlation with anterior uveitis onset. Colocalization analysis supported these findings. Single-cell transcriptome analysis showed predominant AIF1 expression in myeloid cells, which was notably lower in the HLA-B27-positive group. Pseudotime analysis revealed dendritic cell terminal positions in differentiation branches, accompanied by gradual decreases in AIF1 expression. Based on cell communication analysis, CD141+CLEC9A+ classic dendritic cells (cDCs) and the APP pathway play crucial roles in cellular communication in the Spa/HLA-B27 group. Conclusions AIF1 is essential for the pathogenesis of SpA/HLA-B27-associated AAU. Myeloid cell differentiation into DCs and decreased AIF1 levels are also pivotal in this process.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose–effect relationship of acupuncture. Methods/design This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. Discussion This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. Trial registration This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

This study aimed to investigate altered static and dynamic functional network connectivity (FNC) and its correlation with clinical symptoms in patients with knee osteoarthritis (KOA). One hundred and fifty-nine patients with KOA and 73 age- and gender-matched healthy subjects (HS) underwent resting-state functional magnetic resonance imaging (rs-fMRI) and clinical evaluations. Group independent component analysis (GICA) was applied, and seven resting-state networks were identified. Patients with KOA had decreased static FNC within the default mode network (DM), visual network (VS), and cerebellar network (CB) and increased static FNC between the subcortical network (SC) and VS (p < 0.05, FDR corrected). Four reoccurring FNC states were identified using k-means clustering analysis. Although abnormalities in dynamic FNCs of KOA patients have been found using the common window size (22 TR, 44 s), but the results of the clustering analysis were inconsistent when using different window sizes, suggesting dynamic FNCs might be an unstable method to compare brain function between KOA patients and HS. These recent findings illustrate that patients with KOA have a wide range of abnormalities in the static and dynamic FNCs, which provided a reference for the identification of potential central nervous therapeutic targets for KOA treatment and might shed light on the other musculoskeletal pain neuroimaging studies.

Jujube fruits usually suffer from physiological disorders or infectious diseases during storage, leading to quality deterioration, softening, or rotting. Therefore, this study aims to investigate the effect of methionine soaking treatment on the postharvest jujube fruit decay rate and storage quality. Methionine treatment significantly reduced the decay rate of postharvest jujube fruit and effectively maintained fruit color and titratable acid. Methionine treatment effectively delayed the decrease of firmness, soluble solids, ascorbic acid, and lignin contents in jujube fruit. Methionine treatment reduced the content of alanine and phenylalanine, and increased the content of glycine in jujube fruit, but displayed no significant effect on total amino acid content. In addition, jujube fruits in the methionine treatment group had a higher total phenolic and flavonoid content and antioxidant capacity, both in free and bound forms. Compared with the control, methionine treatment also significantly increased the content of individual phenolic acid fractions (gallic acid, vanillic acid, and syringic acid) and flavonoid fractions (catechin, epicatechin, rutin) in free form as well as individual phenolic acid fractions in bound form (gallic acid and ferulic acid) in jujube fruits. Overall, this study suggested that the methionine treatment could be used as a prospective preservative to reduce the postharvest decay of jujube fruit and alleviate its nutritional quality deterioration during cold storage at 4°C.

Abstract Organic small-molecule contrast agents have attracted considerable attention in the field of multispectral optoacoustic imaging, but their weak optoacoustic performance resulted from relatively low extinction coefficient and poor water solubility restrains their widespread applications. Herein, we address these limitations by constructing supramolecular assemblies based on cucurbit[8]uril (CB[8]). Two dixanthene-based chromophores (DXP and DXBTZ) are synthesized as the model guest compounds, and then included in CB[8] to prepare host-guest complexes. The obtained DXP-CB[8] and DXBTZ-CB[8] display red-shifted and increased absorption as well as decreased fluorescence, thereby leading to a substantial enhancement in optoacoustic performance. Biological application potential of DXBTZ-CB[8] is investigated after co-assembly with chondroitin sulfate A (CSA). Benefiting from the excellent optoacoustic property of DXBTZ-CB[8] and the CD44-targeting feature of CSA, the formulated DXBTZ-CB[8]/CSA can effectively detect and diagnose subcutaneous tumors, orthotopic bladder tumors, lymphatic metastasis of tumors and ischemia/reperfusion-induced acute kidney injury in mouse models with multispectral optoacoustic imaging.

Abstract Rheumatoid arthritis (RA) is a debilitating autoimmune disease that causes chronic pain and serious complications, presenting a significant challenge to treat. Promising approaches for treating RA involve signaling pathways modulation and targeted therapy. To this end, a multifunctional nanosystem, TPC‐U@HAT, has been designed for RA therapy, featuring multitargeting, dual‐stimuli response, and on‐demand drug release capabilities. TPC‐U@HAT is composed of a probe/prodrug TPC, a JAK1 kinase inhibitor upadacitinib, and the drug carrier HAT. TPC is composed of an aggregation‐induced emission (AIE)‐active NIR‐II chromophore TPY and an NF‐κB/NLRP3 inhibitor caffeic acid phenethyl ester (CAPE), connected via boronic ester bond which serves as the reactive‐oxygen‐species‐responsive linker. The carrier, HAT, is created by grafting bone‐targeting alendronate and hydrophobic tocopheryl succinate onto hyaluronic acid chains, which can encapsulate TPC and upadacitinib to form TPC‐U@HAT. Upon intravenous injection into mice, TPC‐U@HAT accumulates at inflamed lesions of RA through both active and passive targeting, and the overexpressed hyaluronidase and H2O2 therein cleave the hyaluronic acid polymer chains and boronate bonds, respectively. This generates an AIE‐active chromophore for detection and therapeutic evaluation of RA via both optoacoustic imaging and NIR‐II fluorescent imaging and concomitantly releases CAPE and upadacitinib to exert efficacious therapy by inhibiting NF‐κB/NLRP3 and JAK‐STAT pathways.

While dysbiosis within the intestinal ecosystem has been associated with functional constipation (FC), the mechanisms underlying the interactions between FC and the microbiome remain poorly elucidated. Recent investigations suggested that host microRNAs (miRNAs) can modulate bacterial growth and influence the composition of the gut microbiome. To explore the connection between gut microbiota and fecal miRNAs in FC patients, we initially employed 16S rRNA sequencing to assess the gut microbial landscape in 30 FC patients and 30 healthy controls (HCs). The α-diversity within the FC group exhibited some alterations, and the β-diversity significantly differed, signifying distinctive variations in gut microbiota composition between FC patients and HCs. Subsequently, we identified 44 differentially expressed (DE) miRNAs in feces from FC patients and HCs. Through correlation analysis between DE miRNAs and FC-associated microbiota, we detected an interaction involving nine DE miRNAs (miR-205-5p, miR-493-5p, miR-215-5p, miR-184, miR-378c, miR-335-5p, miR-514a-3p, miR-141-3p, and miR-34c-5p) with seven bacterial genera (Oscillibacter, Escherichia.Shigella, UCG.002, Lachnospiraceae_NK4A136_group, Lachnospiraceae_UCG.010, Eubacterium_ruminantium_group and Megamonas), as evidenced by a co-occurrence network. Further, a comprehensive panel of seven diagnostic biomarkers (Oscillibacter, Escherichia.Shigella, UCG.002, miR-205-5p, miR-493-5p, miR-215-5p, and Lachnospiraceae_NK4A136_group) demonstrated robust discriminatory capacity in predicting FC status when integrated into a random forest model (AUC = 0.832, 95% CI: 65.73–98.88). Microbiomes correlating with DE miRNAs exhibited enrichment in distinct predicted metabolic categories. Moreover, miRNAs correlated with FC-associated bacteria were found to be enriched in signaling pathways linked to colonic contractility, including Axon guidance, PI3K-Akt signaling pathway, MAPK signaling pathway, and Hippo signaling pathway. Our study offers a comprehensive insight into the global relationship between microbiota and fecal miRNAs in the context of FC, presenting potential targets for further experimental validation and therapeutic interventions.

BackgroundType 2 diabetes mellitus (T2DM) is a common condition that is characterized by metabolic impairments. Exercise therapy has proven effective in improving the physiological and psychological states of patients with T2DM; however, the influence of different exercise modalities on metabolic profiles is not fully understood. This study first aimed to investigate the metabolic changes associated with T2DM among patients and then to evaluate the potential physiological effects of different exercise modalities (Tai Chi and brisk walking) on their metabolic profiles.MethodsThis study included 20 T2DM patients and 11 healthy subjects. Patients were randomly allocated to either the Tai Chi or walking group to perform Dijia simplified 24-form Tai Chi or brisk walking (80-100 m/min), with 90 minutes each time, three times per week for 12 weeks, for a total of 36 sessions. The healthy group maintained daily living habits without intervention. Glycemic tests were conducted at the baseline and after 12 weeks. Serum and urine samples were collected for untargeted metabolomic analyses at baseline and 12 weeks to examine the differential metabolic profiles between T2DM and healthy subjects, and the metabolic alterations of T2DM patients before and after exercise therapy.ResultsCompared to the healthy group, T2DM patients exhibited metabolic disturbances in carbohydrates (fructose, mannose, galactose, glycolysis/gluconeogenesis), lipids (inositol phosphate), and amino acids (arginine, proline, cysteine, methionine, valine, leucine, and isoleucine) metabolism, including 20 differential metabolites in the serum and six in the urine. After exercise, the glycemic results showed insignificant changes. However, patients who practiced Tai Chi showed significant improvements in their post-treatment metabolic profiles compared to baseline, with nine serum and six urine metabolites, including branch-chained amino acids (BCAAs); while those in the walking group had significantly altered nine serum and four urine metabolites concerning steroid hormone biosynthesis and arachidonic acid metabolism compared to baseline.ConclusionT2DM patients displayed impaired carbohydrate, lipid, and amino acid metabolism, and exercise therapy improved their metabolic health. Different modalities may act through different pathways. Tai Chi may improve disrupted BCAAs metabolism, whereas brisk walking mainly regulates steroid hormone biosynthesis and arachidonic acid metabolism.

ObjectiveTo systematically summarize current evidence and determine the clinical effectiveness and safety of Tai Chi for type 2 diabetes mellitus (T2DM) in adults by conducting an overview of systematic reviews (SRs).MethodsA systematic search encompassing five electronic databases was conducted until July 30, 2023, to identify relevant systematic reviews (SRs) based on randomized controlled trials (RCTs) concerning Tai Chi for T2DM. The methodological quality of the included SRs was assessed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) and the Risk of Bias in Systematic Reviews (ROBIS) tool. The Preferred Reporting Items for Overview of Systematic Review (PRIO-harms) checklist was used to promote a more balanced reporting of benefits and harms in this overview. Corrected covered area (CCA) was used to calculate the degree of overlapping primary studies. Primary outcome measures were glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG), while secondary outcomes encompassed health-related quality measures. The GRADE (Grades of Recommendations, Assessment, Development, and Evaluation) framework was utilized to assess the quality of evidence for the outcome measures.ResultsA total of 17 eligible SRs were included in this overview. One SR reported negative conclusions, while the remaining 16 reported positive ones on different outcomes. A total of 4 SRs reported adverse events, either absent or minor. Most of the SRs exhibited critically low quality (15/17) and a high risk of bias (14/17), as indicated by AMSTAR2 and ROBIS, respectively. The CCA was 12.14%, indicating a high degree of primary study overlapping. Evidence from 135 results for 24 outcomes concerning Tai Chi for T2DM was evaluated using the GRADE approach, most of which were rated very low.ConclusionTai Chi shows promise as a potentially effective and safe lifestyle intervention for adults with T2DM, particularly in improving HbA1c, FBG, BMI, and overall quality of life (QoL). However, these results should be cautiously interpreted due to methodological flaws observed in the current SRs and the low quality of the SRs based on GRADE. Furthermore, there is a compelling need for additional well-designed, high-quality RCTs and SRs to establish robust and conclusive evidence regarding the efficacy of Tai Chi for managing T2DM in the future.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD 42019140988.

The economic and health significance of quinoa is steadily growing on a global scale. Nevertheless, the primary obstacle to achieving high yields in quinoa cultivation is pre-harvest sprouting (PHS), which is intricately linked to seed dormancy. However, there exists a dearth of research concerning the regulatory mechanisms governing PHS. The regulation of seed germination by various plant hormones has been extensively studied. Consequently, understanding the mechanisms underlying the role of endogenous hormones in the germination process of quinoa seeds and developing strategies to mitigate PHS in quinoa cultivation are of significant research importance. This study employed the HPLC-ESI-MS/MS internal standard and ELISA method to quantify 8 endogenous hormones. The investigation of gene expression changes before and after germination was conducted using RNA-seq analysis, leading to the discovery of 280 differentially expressed genes associated with the regulatory pathway of endogenous hormones. Additionally, a correlation analysis of 99 genes with significant differences identified 14 potential genes that may act as crucial “transportation hubs” in hormonal interactions. Through the performance of an analysis on the modifications in hormone composition and the expression of associated regulatory genes, we posit a prediction that implies the presence of a negative feedback regulatory mechanism of endogenous hormones during the germination of quinoa seeds. This mechanism is potentially influenced by the unique structure of quinoa seeds. To shed light on the involvement of endogenous hormones in the process of quinoa seed germination, we have established a regulatory network. This study aims to offer innovative perspectives on the breeding of quinoa varieties that exhibit resistance to PHS, as well as strategies for preventing PHS.

Abstract Background The aberrance of gray matter morphology in migraineurs has been widely investigated. However, it remains largely unknown whether there are illness duration-related hierarchical changes in the gray matter structure. Methods A total of 86 migraine without aura (MwoA) patients and 73 healthy controls were included. The Voxel-Based Morphometry approach was utilized to compare the gray matter volume (GMV) differences between MwoA patients and healthy controls. The Structural Covariance Network analysis was conducted to quantify the cross-regional synchronous alterations of gray matter structure in MwoA patients. The Causal Structural Covariance Network analysis was performed to describe the progressive and hierarchical changes in the gray matter network of patients in the pathological progression of migraine. Results MwoA patients had duration-stage related GMV hypertrophy in the left parahippocampus, as well as synergistic GMV aberrance in the parahippocampus and the medial inferior temporal gyrus and cerebellum. Moreover, the GMV alteration of the parahippocampus, and the surrounding hippocampus, amygdala, and bilateral anterior cerebellum, preceded and causally influenced the morphological changes of lateral parietal-temporal-occipital gyrus, as well as the motor cortex and prefrontal gyrus with the increasing illness duration in MwoA patients. Conclusion The current study indicated that gray matter structural alterations in the medial inferior temporal gyrus, especially the parahippocampus, is a critical pathological characteristic in MwoA patients, which drives the gray matter structure alteration of other regions. These findings provide further evidence for understanding the progressive gray matter morphological changes in migraine and may facilitate the development of neuromodulation therapies targeting this procession.

The blotched snakehead Channa maculata is an important economical freshwater species in East Asia. However, there has been relatively little research conducted on the correlation between gender and gut microbes. In this study, 36 of 1000 blotched snakeheads were randomly selected for growth performance measurement and gut microbiota high-throughput sequencing. Results showed that microbial diversity, composition, and metabolic functions were altered by gender and growth performance except the microbial network. In our study, Proteobacteria were the most abundant phylum, with Fusobacteria showing enrichment in males and Bacteroidetes in females. Notably, phylum Deinococcus-Thermus was identified as a significant biomarker. The Cetobacterium was the most abundant genus-level taxon. Furthermore, gut microbes specializing in the production of gut-healthy substances, such as coenzymes and vitamins, were identified as biomarkers in the fast-growing group. Our investigation highlighted the impact of gender on the composition and abundance of gut microbial biomarkers in both males and females, thereby influencing differential growth performance through the modulation of specific metabolic functions.

Abstract: Quinoa has been recognized as the sole “comprehensive nutritional crop”; however, it is susceptible to pre-harvest sprouting (PHS). While quantitative reverse transcription polymerase chain reaction (RT-qPCR) has been extensively employed for gene expression level detection, the selection of suitable reference genes is imperative to ensure precise gene expression quantification across diverse conditions. This study aims to identify stable reference genes in quinoa seeds under ABA and GA, in order to provide a basis for subsequent research on PHS. Seeds were subjected to different concentrations of ABA and GA (10 μM, 50 μM, 100 μM, and 200 μM). The most suitable treatment concentration was determined based on seed viability. Here, MON1, GAPDH, EIF3, EF1α, ACT, TUB1, and TUB6 were selected as candidate genes. The suitability of these reference genes under different conditions was assessed using various methods including Ct values, geNorm, NormFinder, BestKeeper, Delta Ct, and RefFinder. Based on the results obtained from the hormone experiments, it was observed that the application of 100 μM ABA and 200 μM GA yielded the most advantageous outcomes. Additionally, the most appropriate reference genes for different treatments are ACT and TUB1 (H2O treatment), EIF3 and MON1 (ABA, GA treatment and also for the combined data set of the three groups). However, GAPDH exhibited the least stability across all treatments. In summary, ACT is recommended as the reference gene for natural quinoa germination, while EIF3 and MON1 should be used for ABA and GA treatments.

BackgroundThe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common respiratory disease among older adults, which imposes a significant burden on individuals and society and poses a major challenge to the global public health system due to its high morbidity and mortality. Acupuncture is effective for AECOPD, but its efficacy has been questioned due to the limited methodological quality. Thus, we aim to investigate the efficacy of acupuncture as adjunctive therapy for AECOPD and determine whether the efficacy of acupuncture differs with the type of acupoint combinations.Methods and analysisThis study proposes a prospective, multicenter randomized controlled trial that will comprise four groups, including two acupuncture treatment groups, one sham acupuncture group, and one basic treatment group. The acupuncture treatment groups will be distinguished by their focus on different patterns of acupoint combination, namely the Xi-cleft and He-sea acupoint combination and the Eight Confluence points acupoint combination, which may vary in clinical efficacy based on traditional acupuncture theories. The study aims to randomize 556 patients in a 1:1:1:1 ratio across the four groups. Each patient in acupuncture group or sham acupuncture group will receive routine drug therapy and 7 sessions of acupuncture treatment over 1 week. Participants in the basic treatment group will only receive routine drug therapy. The trial will be conducted in seven hospitals located in China. The primary outcomes in this trial will include differences in the Breathlessness, Cough, and Sputum Scale (BCSS) before randomization, 7 days after randomization, 5 and 9 weeks after randomization.Ethics and disseminationEthical approval was obtained from the Sichuan Regional Ethics Review of Committee on Traditional Chinese Medicine (Approval ID: 2022KL-068). The results of this study will be distributed through peer-reviewed journals.Clinical Trial Registration: ClinicalTrials.gov, identifier ChiCTR2200064484.

Abstract Background The implementation of the NVBP policy has generated considerable reductions in drug procurement prices and an increase in the market share of the NVBP drugs.This study aimed to investigate patients' attitudes towards switching to drugs of national volume-based procurement (NVBP) and identify their underlying influencing factors in Wuhan, China. Methods A total of 21 eligible patients from the Wuhan Union Hospital who were switched to NVBP drugs between January 2022 and May 2022 were included in our study. Semi-structured face-to-face interviews were conducted to collect interview information and the interview data was analyzed by the Colaizzi seven-step method. Results Twenty-one semi-structured face-to-face interviews were conducted. The duration of each interview was 25–35 min and three themes related to patients' attitudes and their influencing factors were extracted, including (1) Patients' perception of the NVBP drugs; (2) Family and social influence to patients; (3) Medication habits of patients. This study found: 1) 71.4% patients (15/21) showed a positive attitude towards switching to NVBP medicines; 2)80.9% patients (17/21) have felt a significant reduction in their medication cost after the implementation of the NVBP policy; 3)Advices from healthcare professionals and health insurance reimbursement policies showed great impacts on patients' attitude towards switching to NVBP drugs; 4)Attitudes towards switching to NVBP drugs varied considerably among patients with different severities of disease. Conclusion The implementation of the NVBP policy has significantly reduced the cost of healthcare for patients and has been supported by71.4% (15 of 21) patients. However, some issues have been identified in the implementation of the policy in this study. Health professionals in general need to contribute more efforts to improve patients' preconceptions about the NVBP drugs and boost their confidence in the NVBP drugs.

Citrus fruits are rich in phenolic compounds that possess several health benefits. However, few studies have focused on the changes in phenolic compounds in citrus fruits during postharvest storage. This study dynamically monitored the phenolic content, components and antioxidant activity of ‘Tarocco’ blood oranges during a period of 12-week cold storage and on-tree storage, respectively. We investigated the alteration mechanism of phenolic compounds in blood oranges by evaluating phenylpropanoid pathway-related enzyme activities and gene expression. Results showed that flavanones were the main phenolic compounds in blood oranges. Both storage methods mainly stimulated the accumulation of phenolic acids to improve total phenolic content, which reached the maximum at week 12. Nonetheless, blood oranges had a higher phenolic content and antioxidant activity under on-tree storage than cold storage. Furthermore, the enzyme activities and gene expression of the phenylpropanoid pathway demonstrated that the accumulation of phenolics in blood oranges during storage was highly related to the activation of the phenylpropanoid pathway. These results demonstrate that on-tree storage is a potential approach for extending the supply period of blood orange from the perspective of phenolic compounds.

Abstract Background Acupuncture or moxibustion has been proven to be effective for patients with primary dysmenorrhea (PDM). However, the respective advantages and potential central mechanism of acupuncture and moxibustion are worthy of investigating to promote their further application. Methods In this randomized controlled neuroimaging trial, 72 patients with PDM will be randomly assigned to three groups: acupuncture treatment group, moxibustion treatment group, and waiting list group. The acupuncture treatment group and moxibustion treatment group will receive acupuncture or moxibustion, respectively, for a total of 3 sessions over 3 consecutive menstrual cycles, and the waiting list group will not take acupuncture or moxibustion during these 3 menstrual cycles. The COX Menstrual Symptom Scale (CMSS), visual analog scale (VAS), and Pain Catastrophizing Scale (PCS) will be used to evaluate the clinical efficacy. The Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and 36-Item Short Form Health Survey (SF-36) will be used to assess the mental state and quality of life at baseline and at the end of treatment. Functional magnetic resonance imaging (fMRI) will be performed for detecting the cerebral activity changes at baseline and at the end of the treatment. The clinical data and imaging data will be analyzed among the groups. Correlation analysis will be conducted to investigate the relationship between brain functional changes and symptom improvement. Discussion The application of the randomized controlled neuroimaging trial will provide objective and valid evidence about how acupuncture and moxibustion treatment relieve menstrual pain. The results of this study would be useful to confirm the potential similarities and differences between acupuncture and moxibustion in clinical efficacy and central mechanism for patients with PDM. Trial registration Chinese Clinical Trial Registry ChiCTR2100043732 . Registered on 27 February 2021

Introduction: Post-transplant diabetes mellitus (PTDM) is a known side effect in transplant recipients administered immunosuppressant drugs, such as tacrolimus. This study aimed to investigate the risk factors related to PTDM, and establish a risk prediction model for PTDM. In addition, we explored the effect of PTDM on the graft survival rate of kidney transplantation recipients. Methods: Patients with pre-diabetes mellitus before kidney transplant were excluded, and 495 kidney transplant recipients were included in our study, who were assigned to the non-PTDM and PTDM groups. The cumulative incidence was calculated at 3 months, 6 months, 1 year, 2 years, and 3 years post-transplantation. Laboratory tests were performed and the tacrolimus concentration, clinical prognosis, and adverse reactions were analyzed. Furthermore, binary logistic regression analysis was used to identify the independent risk factors of PTDM. Results: Age ≥ 45 years (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 1.14–3.92; P = 0.015), body mass index (BMI) > 25 kg/m2 (aOR 3.12, 95% CI 2.29–5.43, P 10 ng/mL during the first 3 months post-transplantation (aOR 2.46, 95%CI 1.41–7.38; P 25 kg/m2, tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation, transient hyperglycemia, DGF and acute rejection.

Abstract Background Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, with a high prevalence and significant influence on the quality of life (QoL). Either acupuncture or moxibustion is effective for dyspepsia, which is confirmed by both ancient documents and modern research. However, the therapeutic advantage and underlying mechanism between acupuncture and moxibustion for FD remain unclear. Methods This randomized controlled fMRI trial aims to (i) evaluate the therapeutic advantages of acupuncture and moxibustion treatment for FD, (ii) investigate the similarities and differences in cerebral activity elicited by acupuncture and moxibustion, and (iii) analyze the possible correlations between brain responses and clinical variables thus to explore the potential central mechanism of acupuncture and moxibustion for treating FD. Ninety-two FD patients will be randomly assigned to either the acupuncture group or the moxibustion group in a 1:1 ratio. Twenty sessions of acupuncture or moxibustion treatment over 4 weeks will be performed on each patient. The short form Leeds Dyspepsia Questionnaire, the Nepean Dyspepsia Index, etc., are used to evaluate the therapeutic effects. The heart rate variability will be analyzed to investigate the autonomic nerve function. Thirty-six FD patients in each group will be randomly selected for the fMRI scan to detect cerebral activity changes. Discussion We expect the results will deepen our knowledge on the clinical value and underlying mechanism of acupuncture and moxibustion and provide a reference for a better selection of interventions for treating FD. Trial registration Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100049496. Registered on 2 August 2021

BackgroundNeuroimaging studies have identified aberrant activity patterns in multiple brain regions in functional dyspepsia (FD) patients. However, due to the differences in study design, these previous findings are inconsistent, and the underlying neuropathological characteristics of FD remain unclear.MethodsEight databases were systematically searched for literature from inception to October 2022 with the keywords “Functional dyspepsia” and “Neuroimaging.” Thereafter, the anisotropic effect size signed the differential mapping (AES-SDM) approach that was applied to meta-analyze the aberrant brain activity pattern of FD patients.ResultsA total of 11 articles with 260 FD patients and 202 healthy controls (HCs) were included. The AES-SDM meta-analysis demonstrated that FD patients manifested increased activity in the bilateral insula, left anterior cingulate gyrus, bilateral thalamus, right precentral gyrus, left supplementary motor area, right putamen, and left rectus gyrus and decreased functional activity in the right cerebellum compared to the HCs. Sensitivity analysis showed that all these above regions were highly reproducible, and no significant publication bias was detected.ConclusionThe current study demonstrated that FD patients had significantly abnormal activity patterns in several brain regions involved in visceral sensation perception, pain modulation, and emotion regulation, which provided an integrated insight into the neuropathological characteristics of FD.

IntroductionTraditional acupuncture with reinforcing-reducing manipulation is essential for clinical effectiveness, whereas the underlying central mechanism of it remains unknown. This study with multiple-channels functional near-infrared spectroscopy (fNIRS) aims to explore cerebral-response modes during acupuncture with reinforcing-reducing manipulations.Materials and methodsFunctional near-infrared spectroscopy data were recorded from 35 healthy participants during the lifting-thrusting reinforcing manipulation, the lifting-thrusting reducing manipulation, and the even reinforcing-reducing manipulation with lifting-thrusting. The general linear model based (GLM) cortical activation analysis and the functional connectivity (FC) based on region of interest (ROI) analysis were combined to be conducted.ResultsIn comparison with the baseline, the results showed that three acupuncture with reinforcing-reducing manipulations similarly induced the hemodynamic responses in the bilateral dorsolateral prefrontal cortex (DLPFC) and increased FC between the DLPFC and primary somatosensory cortex (S1). Specifically, the even reinforcing-reducing manipulation deactivated the bilateral DLPFC, the frontopolar area (FP), the right primary motor cortex (M1), the bilateral S1, and the bilateral secondary somatosensory cortex (S2); The reducing manipulation deactivated the bilateral DLPFC; The reinforcing manipulation activated the bilateral DLPFC, the left S1, and the right S2. The between-group comparisons indicated that the reinforcing-reducing manipulation induced opposite hemodynamic responses in the bilateral DLPFC and the left S1 and exhibited different FC patterns in the left DLPFC-S1, within the right DLPFC, and between the left S1 and the left orbitofrontal cortex (OFC).ConclusionThese findings verified the feasibility of fNIRS for investigating cerebral functional activities of acupuncture manipulations, suggesting that the regulations on the DLPFC-S1 cortex may be the potential central mechanism for the realization of acupuncture with reinforcing-reducing manipulation’s effect.Clinical trial registrationClinicalTrials.gov, identifier, ChiCTR2100051893.

Heat stress (HS) triggers mammary gland degradation, accompanied by apoptosis and autophagy in bovine mammary epithelial cells, negatively affecting milk performance and mammary gland health. Ferroptosis is iron-mediated regulated cell death caused by over production of lipid peroxides, however, the relationship between ferroptosis and HS in bovine mammary epithelial cells has not been clarified. Methionine (Met) plays a notable role in alleviating HS affecting the mammary glands in dairy cows, but the underlying mechanisms require further exploration. Therefore, we evaluated the regulatory effect and mechanism of Met in alleviating HS-induced ferroptosis by using bovine mammary epithelial cell line (MAC-T) as an in vitro model. The results showed that Met improved cell vitality, restored mitochondrial function; reduced the content of various reactive oxygen species (ROS), especially hydrogen peroxide (H2O2) and superoxide anion (O2·-); had positive effects on antioxidant enzyme activity, namely glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). More importantly, Met reduced labile iron protein (LIP) levels; increased iron storage and simultaneously decreased the levels of lipid reactive oxygen species (lipid ROS) and malondialdehyde (MDA), which all caused by HS in MAC-T. Mechanistically, Met increased the protein expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7, member 11 (SLC7A11) and ferritin heavy chain 1 (FTH1) by activating nuclear factor E2-related factor 2 (Nrf2) expression. Additionally, the protection effect of Met was cut off in MAC-T cells after interference with Nrf2, manifesting in decresing the protein expression levels of GPX4, SLC7A11 and FTH1,and increasing the levels of LIP and lipid ROS. Our findings indicate that Met eases HS-induced ferroptosis in MAC-T through the Nrf2 pathway, revealing that Met produces a marked effect on easing HS-induced bovine mammary gland injury in dairy cows.

We suggest that behind the black hole information paradox is a new and universal radiation mechanism, Gravity Induced Spontaneous Radiation, or GISR hereafter. This mechanism happens to all kinds of compositional objects and it requires only their microscopic structure as the basis. It's always accompanied with such inner structures' variation and allows for explicitly hermitian hamiltonian description. For black holes, by Wigner-Wiesskopf approximation we show that such a radiation has a thermal spectrum exactly the same as hawking radiation; while through numeric integration, we show that the variation of the radiation particles' entropy exhibits all features of Page curve as expected. We also provide exact and analytic solutions to the Einstein equation describing microscopic structures required by the GISR of black holes and show that, after quantisation the degeneracy of wave functions corresponding with those solutions are consistent with the area law formula of Bekenstein-Hawking entropy.

Abstract Humans and plants have become enfolded and inseparable. Abiotic stresses in particular oxidative stress caused by heavy‐metal ions or high‐level salt contamination deleteriously impact plants’ growth process and have become a major threat to sustaining food security. Sprouting is the first step in plants’ growth process. When plant sprouts endure oxidative stress induced by toxic heavy‐metal ions or high‐level salt, accelerated generation of reactive oxygen species (e.g., H2O2) occurs inside plant sprouts; hence in‐situ H2O2 in plant sprouts could serve as the in‐vivo biomarker for tracking the oxidative stress in plant sprouts. Herein, we design an activatable probe CT‐XA‐H2O2 to track the oxidative stress in plant sprouts via in vivo NIR‐II fluorescent imaging. In CT‐XA‐H2O2, cyano‐thiazole acts as the electron‐accepting moiety and xanthane‐aminodiphenyl as the electron‐donating moiety, and dioxaborolane as the biomarker‐responsive unit and fluorescence quencher. The probe CT‐XA‐H2O2 shows weak fluorescent emission. When H2O2 is present, the dioxaborolane in the probe is cleaved, consequently, the dye CT‐XA‐OH is generated and brings about significant fluorescent signals for detecting and imaging the in‐situ biomarker. Moreover, the aminodiphenyl group endues the chromophore (the activated probe) with aggregation‐induced emission characteristics, which ensures stronger fluorescence in the aggregated state in the aqueous milieu. The probe CT‐XA‐H2O2 has been employed in the Cd2+‐ion or high‐level salt (NaCl) induced oxidative stress models of soybean sprouts and peanut sprouts, and the experimental results evidently reveal the probe's ability for in‐situ biomarker‐activatable in‐vivo detection and imaging in the plants' sprouts.

Immune-mediated inflammatory diseases (IMIDs) represent a diverse group of diseases and challenges remain for the current medications. Herein, we present an activatable and targeted nanosystem for detecting and imaging IMIDs foci and treating them through blocking NF-κB/NLRP3 pathways. A ROS-activatable prodrug BH-EGCG is synthesized by coupling a near-infrared chromophore with the NF-κB/NLRP3 inhibitor epigallocatechin-3-gallate (EGCG) through boronate bond which serves as both the fluorescence quencher and ROS-responsive moiety. BH-EGCG molecules readily form stable nanoparticles in aqueous medium, which are then coated with macrophage membrane to ensure the actively-targeting capability toward inflammation sites. Additionally, an antioxidant precursor N-acetylcysteine is co-encapsulated into the coated nanoparticles to afford the nanosystem BH-EGCG&NAC@MM to further improve the anti-inflammatory efficacy. Benefiting from the inflammation-homing effect of the macrophage membrane, the nanosystem delivers payloads (diagnostic probe and therapeutic drugs) to inflammatory lesions more efficiently and releases a chromophore and two drugs upon being triggered by the overexpressed in-situ ROS, thus exhibiting better theranostic performance in the autoimmune hepatitis and hind paw edema mouse models, including more salient imaging signals and better therapeutic efficacy via inhibiting NF-κB pathway and suppressing NLRP3 inflammasome activation. This work may provide perceptions for designing other actively-targeting theranostic nanosystems for various inflammatory diseases.

The fresh postharvest golden needle mushroom (Flammulina velutipes) sporocarp has a high moisture content and crisp texture, but it still has high physiological activity and respiration, leading to senescence and quality deterioration. Treatments with 1-methylcyclopropene (1-MCP) and polypropylene (PP) crispers were used to study the changes of lignification and softening of F. velutipes during storage. The main findings were as follows: the crisper packaging could effectively prolong the storage time of F. velutipes; either the 1-MCP treatment, crisper packaging or the combination of the two treatments could significantly inhibit the accumulation of lignin and the decreases in the contents of cellulose and pectin, and had certain inhibitory effects on the activities of enzymes involved in lignification and softening including phenylalanine ammonia-lyase (PAL), cinnamyl alcohol dehydrogenase (CAD), cellulase (Cx), pectin methylesterase (PME) and polygalacturonase (PG). Among them, the inhibitory effect of the crisper packaging was higher than the 1-MCP treatment, while the combination of the two treatments was the best. The results of transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed that the crisper packaging in combination with the 1-MCP treatment could effectively maintain the integrity and stability of the F. velutipes cellular structure and inhibit the emergence of plasmolysis to prevent cell membrane rupture. The transcription levels showed that the crisper packaging and the combination of the 1-MCP treatment and crisper packing could effectively affect the expression of genes for enzymes related to lignification and softening of F. velutipes. In conclusion, 1-MCP and PP crispers could delay the lignification and softening of F. velutipes during storage.

Background: Acupuncture reinforcing-reducing manipulation (ARRM) is a necessary procedure of traditional Chinese acupuncture and an essential factor affecting the therapeutic effect of acupuncture. Shaoshanhuo reinforcing method (SSH) and Toutianliang reducing method (TTL) are the most representative ARRMs. They integrate six single ARRMs and pose distinguished therapeutic effects of acupuncture. However, due to the complexity, diversity, and variation, investigating the mechanism of these two classic manipulations is insufficient. The neuroimaging technique is an important method to explore the central mechanism of SSH and TTL. This study attempted to design a randomized crossover trial based on functional near-infrared spectroscopy (fNIRS) to explore the mechanism of SSH and TTL, meanwhile, provide valuable methodological references for future studies.Methods: A total of 30 healthy subjects were finally included and analyzed in this study. fNIRS examination was performed to record the neural responses during the two most representative ARRMs. The cortical activation and the inter-network functional connectivity (FC) were explored.Results: The results found that SSH and TTL could elicit significant cerebral responses, respectively, but there was no difference between them.Conclusion: Neuroimaging techniques with a higher spatiotemporal resolution, combinations of therapeutic effects, and strict quality control are important to neuroimaging studies on SSH and TTL.

Dasatinib, a second-generation tyrosine kinase inhibitor, is recommended as first-line treatment for patients newly diagnosed with chronic myeloid leukemia (CML) and second-line treatment for those who are resistant or intolerant to therapy with imatinib. Dasatinib is superior to imatinib in terms of clinical response; however, the potential pulmonary toxicities associated with dasatinib, such as pulmonary arterial hypertension and pleural effusion, may limit its clinical use. Appropriate management of dasatinib-related severe events is important for improving the quality of life and prognosis of patients with CML. This review summarizes current knowledge regarding the characteristics, potential mechanisms, and clinical management of adverse reactions occurring after treatment of CML with dasatinib.

Microbiome epidemiology is an emerging field for the discovery of novel disease biomarkers or intervention targets in human epidemiological studies. The determinants and consequences of human microbiome variations, especially for the gut microbiome, are both important and unsolved research questions, while the majority of findings of prior research are based on small-scale human studies with limited statistical power and a lack of replication/generalizability across different populations. Here, we initiated the Westlake Gut (WeGut) project, a consortium of gut microbiome-based human cohort studies in China. The WeGut project aims to provide a platform for the integration of gut microbiome data across different cohort studies, including two major components: 1) cohorts for healthy ageing and 2) cohorts for healthy pregnancy. The WeGut consortium includes seven core/foundation cohorts involving over 32,000 participants with gut microbiome and rich phenotype data across 17 provinces/megacities in China. Within the WeGut framework, we hope to disentangle the interplay among diet, lifestyle factors, host genetics and the gut microbiome in human health and explore the role of the gut microbiome for the precision prevention of chronic diseases in Chinese populations.

Fluorescent imaging in the second biological window has advantages for in vivo applications. Here, the authors synthesise a molecular nanoprobe which activates upon binding H2O2, generating both strong fluorescent NIR-II emission and ultrasound signal for multi-mode imaging of inflammatory diseases.

Abstract With global warming, heat stress has become an important challenge for the global dairy industry. Sirtuin 3 (SIRT3), an important mitochondrial NAD+dependent decarboxylase and a major regulator of cellular energy metabolism and antioxidant defense, is integral to maintaining normal mitochondrial function. The aim of this study was to assess the protective effect of SIRT3 on damage to bovine mammary epithelial cells (BMECs) induced by heat stress and to explore its potential mechanism. Our results indicate that SIRT3 is significantly downregulated in heat-stressed mammary tissue and high-temperature-treated BMECs. SIRT3 knockdown significantly increased the expression of HSP70, Bax, and cleaved-caspase 3 and inhibited the production of antioxidases, thus promoting ROS production and cell apoptosis in BMECs. In addition, SIRT3 knockdown can aggravate mitochondrial damage by mediating the expression of genes related to mitochondrial fission and fusion, including dynamin-related protein 1, mitochondrial fission 1 protein, and mitochondrial fusion proteins 1and 2. In addition, SIRT3 knockdown substantially decreased AMPK phosphorylation in BMECs. In contrast, SIRT3 overexpression in high-temperature treatment had the opposite effect to SIRT3 knockdown in BMECs. SIRT3 overexpression reduced mitochondrial damage and weakened the oxidative stress response of BMECs induced by heat stress and promoted the phosphorylation of AMPK. Taken together, our results indicate that SIRT3 can protect BMECs from heat stress damage through the AMPK signaling pathway. Therefore, the reduction of oxidative stress by SIRT3 may be the primary molecular mechanism underlying resistance to heat stress in summer cows.

Abstract Aims/Introduction The current literature suggests that men with diabetes have a lower prostate‐specific antigen concentration than men without diabetes, but the causal association remains unclear. We aimed to investigate the association between serum prostate‐specific antigen concentrations and the risk of type 2 diabetes mellitus in a cohort study of a Chinese population. Materials and Methods We designed a cohort study that comprised 16,811 initially non‐diabetic Chinese men who received annual health checkups between 2009 and 2016. The outcome of this study was type 2 diabetes mellitus, identified by medical diagnosis, self‐reportage, medication use, fasting glucose, 2‐h post oral glucose or glycated hemoglobin measurements. Cox proportional hazards models were carried out to evaluate the association. Results During a median follow‐up period of 3.8 years (interquartile range 1.91–5.73 years), 1,260 participants developed incident type 2 diabetes mellitus. The multivariable model, adjusted for various potential confounders, showed that serum prostate‐specific antigen concentrations were inversely related to type 2 diabetes mellitus risk (P for trend = 0.014). Compared with the lowest quartile of serum prostate‐specific antigen, the hazard ratio and 95% confidence intervals of type 2 diabetes mellitus risk for quartile 2–4 were 0.84 (0.66–1.07), 0.75 (0.59–0.94) and 0.77 (0.62–0.96), respectively. Subgroup analyses suggested the inverse relationship was more prominent in overweight or obese participants (P for interaction = 0.013). Conclusions High serum prostate‐specific antigen concentration was associated with a low risk of type 2 diabetes mellitus in Chinese men. Future studies are required to confirm these findings and investigate underlying mechanisms.

With continued expansion of the aged population, the number of patients with retinal degeneration, which is a leading cause of vision loss worldwide, is growing. Stem cell therapies offer hope for regeneration and repair of damaged retinal tissue. Recent reports have highlighted stem cell-derived paracrine mediators, such as exosomes, which appear to exert a therapeutic benefit similar to their cell of origin and do not carry the risk of cell transplantation. One speculated role is that exosomes likely mediate intercellular communication and material exchange. This review depicts the molecular mechanisms underlying exosome-based therapy, especially in retina degeneration diseases. In the future, the use of stem cell-derived exosomes could be considered a novel and cell-free therapeutic strategy in regenerative medicine.

BackgroundPrevious studies showed conflicting evidence on the association between the intake of dietary branched-chain amino acid (BCAA) and the risk of cardiovascular disease (CVD). However, this relationship has not been studied in patients with type 2 diabetes. Therefore, we evaluated the effects of total and individual dietary BCAA (leucine, isoleucine, and valine) intake on CVD risk among individuals with type 2 diabetes in China.Materials and methodsA total of 419 patients with type 2 diabetes who have been diagnosed with CVD (within 2 weeks) were recruited between March 2013 and September 2015 in China. Cases with CVD were 1:1 matched to controls with type 2 diabetes but without CVD by age (±5 years) and sex. A validated 79-item semiquantitative food frequency questionnaire (FFQ) was administered to assess the participants' dietary data. Total dietary BCAA per individual was the summation of the daily intake of isoleucine, leucine, and valine. OR and corresponding CIs were computed by conditional logistic regression models adjusted for potential confounders.ResultsMedian values of the daily intake of total BCAA were 11.87 g, with an interquartile range of 10.46–13.15 g for cases, and 12.47 g, with an interquartile range of 11.08–13.79 g for controls (P = 0.001). Dietary BCAA was inversely related to CVD risk after multivariable adjustment (OR Q4−Q1 = 0.23, 95%CI = 0.10, 0.51, P trend

IntroductionAcupuncture is an effective and safe therapy for patients with migraine without aura (MwoA), but only 41–59% of patients show improvement with this treatment. Screening positive responders to acupuncture treatment for MwoA can ensure that healthcare resources can be appropriately targeted to specific patients who would most benefit. The objective of this study is to determine whether the structure and functional activity in certain brain regions can predict analgesia response in patients with MwoA who receive acupuncture treatment.Methods and analysisA total of 72 patients with MwoA and 72 healthy controls (HCs) will be enrolled in this study. Resting-state structural and functional magnetic resonance imaging (MRI) data will be collected from each participant at baseline. Patients with MwoA will undergo 12 sessions of acupuncture treatment for 8 weeks, twice per week in the first 4 weeks and once per week for the last 4 weeks. The follow-up will be 12 weeks. The number of days with migraine, frequency of migraine attacks, and average visual analog scale scores will be recorded in detail at weeks 0, 4, 8, 12, and 16 and at the end of follow-up (week 20). The positive response rate will be calculated as the proportion of patients with ≥50% reduction in the number of migraine days during follow-up compared with baseline. Machine learning methods will be applied to classify patients with MwoA and HCs and predict patients with response or non-response to acupuncture treatment based on multimodal MRI parameters, such as gray matter volume, regional homogeneity, amplitude of low-frequency fluctuation, fractional anisotropy, and mean diffusivity.DiscussionThis study aims to establish brain structural and functional characteristics that can identify patients with MwoA who will derive analgesia benefits from acupuncture treatment.Trial registration numberhttp://www.chictr.org.cn/showproj.aspx?proj=65443, identifier: ChiCTR2100042915.