iGWAS: Image-based genome-wide association of self-supervised deep phenotyping of retina fundus images.

Existing imaging genetics studies have been mostly limited in scope by using imaging-derived phenotypes defined by human experts. Here, leveraging new breakthroughs in self-supervised deep representation learning, we propose a new approach, image-based genome-wide association study (iGWAS), for identifying genetic factors associated with phenotypes discovered from medical images using contrastive learning. Using retinal fundus photos, our model extracts a 128-dimensional vector representing features of the retina as phenotypes. After training the model on 40,000 images from the EyePACS dataset, we generated phenotypes from 130,329 images of 65,629 British White participants in the UK Biobank. We conducted GWAS on these phenotypes and identified 14 loci with genome-wide significance (p<5×10-8 and intersection of hits from left and right eyes). We also did GWAS on the retina color, the average color of the center region of the retinal fundus photos. The GWAS of retina colors identified 34 loci, 7 are overlapping with GWAS of raw image phenotype. Our results establish the feasibility of this new framework of genomic study based on self-supervised phenotyping of medical images.

Synthetic BZLF1-targeted transcriptional activator for efficient lytic induction therapy against EBV-associated epithelial cancers.

The unique virus-cell interaction in Epstein-Barr virus (EBV)-associated malignancies implies targeting the viral latent-lytic switch is a promising therapeutic strategy. However, the lack of specific and efficient therapeutic agents to induce lytic cycle in these cancers is a major challenge facing clinical implementation. We develop a synthetic transcriptional activator that specifically activates endogenous BZLF1 and efficiently induces lytic reactivation in EBV-positive cancer cells. A lipid nanoparticle encapsulating nucleoside-modified mRNA which encodes a BZLF1-specific transcriptional activator (mTZ3-LNP) is synthesized for EBV-targeted therapy. Compared with conventional chemical inducers, mTZ3-LNP more efficiently activates EBV lytic gene expression in EBV-associated epithelial cancers. Here we show the potency and safety of treatment with mTZ3-LNP to suppress tumor growth in EBV-positive cancer models. The combination of mTZ3-LNP and ganciclovir yields highly selective cytotoxic effects of mRNA-based lytic induction therapy against EBV-positive tumor cells, indicating the potential of mRNA nanomedicine in the treatment of EBV-associated epithelial cancers.

Co-localization and analysis of miR477b with fiber length quantitative trait loci in cotton.

Cotton is an important cash crop for the textile industry. However, the understanding of natural genetic variation of fiber elongation in relation to miRNA is lacking. A miRNA gene (miR477b) was found to co-localize with a previously mapped fiber length (FL) quantitative trait locus (QTL). The miR477b was differentially expressed during fiber elongation between two backcross inbred lines (BILs) differing in FL and its precursor sequences. Bioinformatics and qRT-PCR analysis were further used to analyse the miRNA genes, which could produce mature miR477b. Cotton plants with virus-induced gene silencing (VIGS) constructs to over-express the allele of miR477b from the BIL with longer fibers had significantly longer fibers as compared with negative control plants, while the VIGS plants with suppressed miRNA expression had significantly shorter fibers. The expression level of the target gene (DELLA) and related genes (RDL1 and EXPA1 for DELLA through HOX3 protein) in the two BILs and/or the VIGS plants were generally congruent, as expected. This report represents one of the first comprehensive studies to integrate QTL linkage mapping and physical mapping of small RNAs with both small and mRNA transcriptome analysis, followed by VIGS, to identify candidate small RNA genes affecting the natural variation of fiber elongation in cotton.

Release and Degradation Mechanism of Modified Polyvinyl Alcohol-Based Double-Layer Coated Controlled-Release Phosphate Fertilizer.

This study aims to improve the slow-release performance of a film material for a controlled-release fertilizer (CRF) while enhancing its biodegradability. A water-based biodegradable polymer material doped with biochar (BC) was prepared from modified polyvinyl alcohol (PVA) with polyvinylpyrrolidone (PVP) and chitosan (CTS), hereinafter referred to as PVA/PVP-CTSaBCb. An environmentally friendly novel controlled-release phosphate fertilizer (CRPF) was developed using PVA/PVP-CTS8%BC7% as the film. The effect of the PVA/PVP-CTS8%BC7% coating on the service life of the CRPF was investigated. The film was characterized via stress-strain testing, SEM, FTIR, XRD, and TGA analyses. The addition of the CTS modifier increased the stress of PVA/PVP-CTS8% by 7.6% compared with that of PVA/PVP owing to the decrease in the crystallinity of PVP/PVP-CTS8%. The hydrophilic -OH groups were reduced due to the mixing of CTS and PVA/PVP. Meanwhile, the water resistance of the PVA/PVP-CTS8%BC7% was improved. And the controlled-release service life of the CRPF was prolonged. Moreover, the addition of BC increased the crystallinity of the PVA/PVP-CTS8% by 10%, reduced the fracture elongation of the material, and further improved the biodegradability of the PVA/PVP-CTS8%BC7%. When the amount of BC added was 7%, the phosphorus release rate of the CRPF was 30% on the 28th day. Moreover, the degradation rate of the PVA/PVP-CTS8%BC7% polymer film was 35% after 120 days. This study provides basic data for applying water-based degradable polymer materials in CRFs.

Nutrient budgets and biogeochemical dynamics in the coastal regions of northern Beibu Gulf, South China Sea: Implication for the severe impact of human disturbance.

This study examined the nutrient budgets and biogeochemical dynamics in the coastal regions of northern Beibu Gulf (CNBG). Nutrient concentrations varied spatially and seasonally among the different bays. High nutrient levels were found in the regions with high riverine inputs and intensive mariculture. Using a three end-member mixing model, nutrient biogeochemistry within the ecosystem was estimated separately from complex physical mixing effects. Nutrient consumption dominated in most bays in summer, whereas nutrient regeneration dominated in winter, likely due to phytoplankton decomposition, vertical mixing and desorption. Through the Land-Ocean Interaction Coastal Zone (LOICZ) model, the robust nutrient budgets were constructed, indicating that the CNBG behaved as a sink of dissolved inorganic nitrogen, phosphorus and silicon. River-borne nutrient inputs were the dominant nutrient source, while residual flows and water exchange flows transported nutrient off the estuaries. This study could help us better understand nutrient cycles and nutrient sources/sinks in the CNBG.

A Novel Prolene Suture Pull-out Technique Combined with Anchor Technique for the Treatment of Tendinous Mallet Finger.

Background: Mallet finger deformity is a prevalent disability that causes discomfort and inconvenience to the patients. Despite the existence of various surgical approaches, surgical management remains a controversial subject. Methods: We retrospectively analyzed the clinical data of 26 patients with isolated tendinous mallet fingers who were admitted between January 2021 and June 2022. Among them, there were 18 men and eight women, aged between 20 and 56 years, with an average age of 38 years. The causes of injury were cutting injuries (15 cases), sports impact injuries (nine cases), and sprains (two cases). The time interval between injury and surgery ranged from 2 hours to 48 days, with an average of 12 days. During the surgical procedure, the distal interphalangeal joint was fixed in a mild dorsiflexion position using Kirschner wire. Absorbable anchors were used to assist in the reconstruction of the insertion point of the finger extensor tendon. Additionally, a 4-0 Prolene suture was used for reinforcement. Results: All 26 patients were followed up for a period ranging from 6 to 24 months, with an average follow-up duration of 9 months. The function of distal interphalangeal joint was preserved. According to the Crawford functional evaluation criteria, the function of the affected fingers was excellent in 15 cases, good in eight cases, fair in three cases, and poor in no cases. Conclusions: A novel Prolene suture pull-out technique is an effective approach to repair tendon mallet finger and reconstruct the tendon-bone anatomical unit. This treatment option provides favorable outcomes, with high rates of excellent and good functional results.

Genomic and co-expression network analyses reveal candidate genes for oil accumulation based on an introgression population in Upland cotton (Gossypium hirsutum).

KEY MESSAGE: Integrated QTL mapping and WGCNA condense the potential gene regulatory network involved in oil accumulation. A glycosyl hydrolases gene (GhHSD1) for oil biosynthesis was confirmed in Arabidopsis, which will provide useful knowledge to understand the functional mechanism of oil biosynthesis in cotton. Cotton is an economical source of edible oil for the food industry. The genetic mechanism that regulates oil biosynthesis in cottonseeds is essential for the genetic enhancement of oil content (OC). To explore the functional genomics of OC, this study utilized an interspecific backcross inbred line population to dissect the quantitative trait locus (QTL) interlinked with OC. In total, nine OC QTLs were identified, four of which were novel, and each QTL explained 3.62-34.73% of the phenotypic variation of OC. The comprehensive transcript profiling of developing cottonseeds revealed 3,646 core genes differentially expressed in both inbred parents. Functional enrichment analysis determined 43 genes were annotated with oil biosynthesis processes. Implementation of weighted gene co-expression network analysis showed that 803 differential genes had a significant correlation with the OC phenotype. Further integrated analysis identified seven important genes located in OC QTLs. Of which, the GhHSD1 gene located in stable QTL qOC-Dt3-1 exhibited the highest functional linkages with the other network genes. Phylogenetic analysis showed significant evolutionary differences in the HSD1 sequences between oilseed- and starch- crops. Furthermore, the overexpression of GhHSD1 in Arabidopsis yielded almost 6.78% higher seed oil. This study not only uncovers important genetic loci for oil accumulation in cottonseed, but also provides a set of new candidate genes that potentially influence the oil biosynthesis pathway in cottonseed.

Aptamer-based flares hybridized with single-stranded DNA-conjugated MoS2 nanosheets for ratiometric fluorescence sensing and imaging of potassium ions and adenosine triphosphate in human fluids and living cells.

Addressing the limitations observed in previous studies, where the quantitative range of nanoprobes for detecting K+ and adenosine triphosphate (ATP) did not cover concentrations found within living cells, the present study aimed to develop ratiometric nanoprobes that can accurately sense changes in K+ and ATP levels in living cells and quantify them in human fluids. The proposed nanoprobes consisted of recognition flares modified with 6-carboxyfluorescein (FAM) and 5-carboxytetramethylrhodamine (TAMRA), along with thiolate single-stranded DNA (ssDNA) and molybdenum disulfide nanosheets (MoS2 NSs). The thiolate ssDNA acts as a linker between the flares and the MoS2 NSs, directly forming a functional nanostructure at room temperature. The direct conjugation of labeled flares to the MoS2 NSs simplifies the fabrication process. In the absence of K+ and ATP, the hybridization of flares and thiolate ssDNA caused FAM to move away from TAMRA, suppressing the fluorescence resonance energy transfer (FRET) process. However, upon the introduction of K+ and ATP, the flares undergo a structural transformation via the formation of G-quadruplex formation and the generation of hairpin-shaped structures, respectively. This structural change leads to the release of the flares from the ssDNA-conjugated nanosheet surface. The release of the flares brings FAM and TAMRA into close proximity, allowing FRET to occur, leading to FRET and static quenching. By monitoring the ratio between the fluorescence intensities of FAM and TAMRA, the concentration of K+ (5-100 mM) and ATP (0.3-5 mM) can be accurately determined by the proposed nanoprobes. The advantages of these nanoprobes lie in their ability to provide ratiometric measurements, which enhance the accuracy and reliability of the quantification process. The proposed nanoprobes offer potential applications as ratiometric imaging probes for monitoring K+ and ATP-related reactions in living cells, providing valuable insights into cellular processes. Additionally, they can be employed for determining the levels of K+ and ATP in human fluids, offering potential diagnostic applications in various clinical settings.

Effectiveness of Telecare Interventions on Depression Symptoms Among Older Adults: Systematic Review and Meta-Analysis.

BACKGROUND: Depression is the most common psychiatric disorder among older adults. Despite the effectiveness of pharmacological and psychological therapies, many patients with late-life depression (LLD) are unable to access timely treatment. Telecare has been shown to be effective in addressing patients' psychosocial issues, while its effectiveness in serving patients with LLD remains unclear. OBJECTIVE: This study aimed to evaluate the effectiveness of telecare in reducing depression and anxiety symptoms and improving quality of life (QoL) in patients with LLD. METHODS: Databases including the Cochrane Library, Web of Science, PubMed, Embase, and EBSCO were searched for randomized controlled trials (RCTs) evaluating the effectiveness of telecare for LLD from database establishment to December 28, 2022. RESULTS: A total of 12 RCTs involving 1663 participants were identified in this study. The meta-analysis showed that (1) telecare significantly reduced depressive symptoms in patients with LLD compared to those in usual care (UC; standardized mean difference [SMD]=-0.46, 95% CI -0.53 to -0.38; P<.001), with the best improvement observed within 3 months of intervention (SMD=-0.72, 95% CI -1.16 to -0.28; P<.001); (2) other scales appeared more effective than the Patient Health Questionnaire-9 for LLD in telecare interventions (SMD=-0.65, 95% CI -0.96 to -0.35; P<.001); (3) telecare was more effective than telephone-based interventions for remote monitoring of LLD (SMD=-1.13, 95% CI -1.51 to -0.76; P<.001); (4) the reduction of depressive symptoms was more pronounced in patients with LLD with chronic conditions (SMD=-0.67, 95% CI -0.89 to -0.44; P<.001); (5) telecare was more effective for LLD in Europe and the Americas than in other regions (SMD=-0.73, 95% CI -0.99 to -0.47; P<.001); (6) telecare significantly reduced anxiety symptoms in patients with LLD (SMD=-0.53, 95% CI -0.73 to -0.33; P=.02); and (7) there was no significant improvement in the psychological components of QoL in patients with LLD compared to those receiving UC (SMD=0.30, 95% CI 0.18-0.43; P=.80). CONCLUSIONS: Telecare is a promising modality of care for treatment, which can alleviate depression and anxiety symptoms in patients with LLD. Continued in-depth research into the effectiveness of telecare in treating depression could better identify where older patients would benefit from this intervention.

Oral Troxerutin Alleviates Depression Symptoms in Mice by Modulating Gut Microbiota and Microbial Metabolism.

SCOPE: A growing body of evidence suggests that the harmful gut microbiota in depression patients can play a role in the progression of depression. There is limited research on troxerutin's impact on the central nervous system (CNS), especially in depression. The study finds that troxerutin effectively alleviates depression and anxiety-like behavior in mice by increasing the abundance of beneficial bacteria like Lactobacillus and Firmicutes while decreasing the abundance of harmful bacteria like Proteobacteria, Bacteroides, and Actinobacteria in the gut. Furthermore, the research reveals that troxerutin regulates various metabolic pathways in mice, including nucleotide metabolism, caffeine metabolism, purine metabolism, arginine biosynthesis, histidine metabolism, 2-oxocarboxylic acid metabolism, biosynthesis of amino acids, glycine, serine and threonine metabolism, and Arginine and proline metabolism. CONCLUSIONS: In conclusion, the study provides compelling evidence for the antidepressant efficacy of troxerutin. Through the investigation of the role of intestinal microorganisms and metabolites, the study identifies these factors as key players in troxerutin's ability to prevent depression. Troxerutin achieves its neuroprotective effects and effectively prevents depression and anxiety by modulating the abundance of gut microbiota, including Proteobacteria, Bacteroides, and Actinobacteria, as well as regulating metabolites such as creatine.

EB1C forms dimer and interacts with protein phosphatase 2A (PP2A) to regulate fiber elongation in upland cotton (Gossypium hirsutum).

Cotton is the most economically important natural fiber crop grown in more than sixty-five countries of the world. Fiber length is the main factor affecting fiber quality, but the existing main varieties are short in length and cannot suit the higher demands of the textile industry. It is necessary to discover functional genes that enable fiber length improvement in cotton through molecular breeding. In this study, overexpression of GhEB1C in Arabidopsis thaliana significantly promotes trichomes, tap roots, and root hairs elongation. The molecular regulation of GhEB1C involves its interactions with itself and GhB'ETA, and the function of GhEB1C regulation mainly depends on the two cysteine residues located at the C-terminal. In particular, the function activity of GhEB1C protein triggered with the regulation of protein phosphatase 2A, while silencing of GhEB1C in cotton significantly influenced the fiber protrusions and elongation mechanisms., Further, influenced the expression of MYB-bHLH-WD40 complex, brassinosteroids, and jasmonic acid-related genes, which showed that transcriptional regulation of GhEB1C is indispensable for cotton fiber formation and elongation processes. Our study analyzed the brief molecular mechanism of GhEB1C regulation. Further elucidated that GhEB1C can be a potential target gene to improve cotton fiber length through transgenic breeding.

Exploration of the mechanism of reinfusion of fresh autologous blood in type 2 diabetes mice to induce macrophage polarization and inhibit erythrocyte damage.

AIMS/INTRODUCTION: Type 2 diabetes triggers an inflammatory response that can damage red blood cells. M2 macrophages have inhibitory effects on inflammation, and play an important role in tissue damage repair and fibrosis. Autologous blood transfusion has the potential to inhibit red blood cell damage by mediating macrophage polarization. MATERIALS AND METHODS: Swiss mice were used to establish a suitable type 2 diabetes model, and autologous blood transfusion was carried out. The mice were killed, the blood of the mice was collected and CD14+ monocytes were sorted. The expression levels of phenotypic molecules CD16, CD32 and CD206 in CD14+ monocytes were analyzed by flow cytometry. The proportion of M1 and M2 macrophages were analyzed by flow cytometry. The Q value, P50 , 2,3-diphosphoglycerate and Na+ -K+ -ATPase of red blood cells were detected. The red blood cell osmotic fragility test analyzed the red blood cell osmotic fragility. Western blot analysis was used to analyze the expression changes of erythrocyte surface membrane proteins or transporters erythrocyte membrane protein band 4.1, sphingosine-1-phosphate, glycolipid transfer protein and signal peptide peptidase-like 2A. RESULTS: Autologous blood transfusion induced a significant increase in the number of macrophages. The state and capacity of blood cells improved with autologous blood transfusion. Reinfusion of fresh autologous blood in type 2 diabetes mice made erythrocytes shrink. The expression of erythrocyte-related proteins proved that the erythrocyte injury in the reinfusion of fresh autologous blood + type 2 diabetes group was significantly reduced. CONCLUSION: The reinfusion of fresh autologous blood into the body of patients with type 2 diabetes can induce macrophage polarization to M2, thereby inhibiting red blood cell damage.

miR-29c-3p acts as a tumor promoter by regulating ß-catenin signaling through suppressing DNMT3A, TET1 and HBP1 in ovarian carcinoma.

Ovarian Carcinoma (OvCa) is characterized by rapid and sustained growth, activated invasion and metastasis. Studies have shown that microRNAs recruit and alter the expression of key regulators to modulate carcinogenesis. Here, we find that miR-29c-3p is increased in benign OvCa and malignant OvCa compared to normal ovary. Univariate and multivariate analyses report that miR-29c-3p overexpression is associated with poor prognosis in OvCa. Furthermore, we investigate that expression of miR-29c-3p is inversely correlated to DNA methyltransferase (DNMT) 3 A and Ten-Eleven-Translocation enzyme TET1. The high-throughput mRNA sequencing, bioinformatics analysis and pharmacological studies confirm that aberrant miR-29c-3p modulates tumorigenesis in OvCa cells, including epithelial-mesenchymal transition (EMT), proliferation, migration, and invasion. This modulation occurs through the regulation of ß-catenin signaling by directly targeting 3'UTR of DNMT3A, TET1 and the HMG box transcription factor HBP1 and suppressing their expression. The further 3D spheres assay clearly shows the regulatory effects of miR-29c-3p on OvCa tumorigenesis. Additionally, the receiver operating characteristic (ROC) curve analysis of miR-29c-3p and the clinical detection/diagnostic biomarker CA125 suggests that miR-29c-3p may be conducive for clinical diagnosis or co-diagnosis of OvCa. These findings support miR-29c-3p functions as a tumor promoter by targeting its functional targets, providing new potential biomarker (s) for precision medicine strategies in OvCa.

Co-delivery of indomethacin and uricase as a new strategy for inflammatory diseases associated with high uric acid.

Uric acid is the final metabolite in humans. High level of uric acid chronically induces urate deposition, aggravates kidney damage, and concomitantly causes an increase in inflammatory factors. Alleviating acute inflammation and decreasing uric acid levels are the key points in the treatment of inflammatory diseases associated with high uric acid. However, a drug delivery system that combines anti-inflammatory and uric acid reduction functions at the same time remains a challenge to be settled. Here, we designed a nanocrystal-based co-delivery platform, IND Nplex, characterized by loading of indomethacin (IND) and uricase. Compared with free IND or uricase, IND Nplex possessed a better anti-inflammatory effect by restraining the release of inflammation-related factors in vitro. In addition, pharmacokinetic and biodistribution studies revealed that IND Nplex significantly prolonged the retention time in vivo and was more concentrated in the kidney. In acute gouty arthritis model rats, IND Nplex markedly relieved ankle joint swelling and mitigated synovial inflammation. In acute kidney injury model rats, IND Nplex indicated better biocompatibility and significant amelioration of renal fibrosis. Moreover, IND Nplex showed the effect of anti-inflammatory and improved renal function via determination of inflammatory factors and biochemical markers in the serum and kidney. In conclusion, these results indicate that IND Nplex exerts anti-inflammatory activity and uric acid-lowering effect and could become a promising candidate for the treatment of uric acid-related diseases. In this study, a stable neutral co-delivery platform (IND Nplex) was fabricated by using a co-delivery strategy, allowing for a combination of the anti-inflammation drug IND and the metabolic enzyme uricase. IND Nplex showed a good therapeutic effect on rats with acute gouty arthritis or acute kidney injury due to the dual effects of anti-inflammatory and uric acid lowering. This platform provided a novel strategy for high uric acid-related illnesses.

Oil candidate genes in seeds of cotton (Gossypium hirsutum L.) and functional validation of GhPXN1.

BACKGROUND: Cottonseed oil is a promising edible plant oil with abundant unsaturated fatty acids. However, few studies have been conducted to explore the characteristics of cottonseed oil. The molecular mechanism of cottonseed oil accumulation remains unclear. RESULTS: In the present study, we conducted comparative transcriptome and weighted gene co-expression network (WGCNA) analysis for two G. hirsutum materials with significant difference in cottonseed oil content. Results showed that, between the high oil genotype 6053 (H6053) and the low oil genotype 2052 (L2052), a total of 412, 507, 1,121, 1,953, and 2,019 differentially expressed genes (DEGs) were detected at 10, 15, 20, 25, and 30 DPA, respectively. Remarkably, a large number of the down-regulated DEGs were enriched in the phenylalanine metabolic processes. Investigation into the dynamic changes of expression profiling of genes associated with both phenylalanine metabolism and oil biosynthesis has shed light on a significant competitive relationship in substrate allocation during cottonseed development. Additionally, the WGCNA analysis of all DEGs identified eight distinct modules, one of which includes GhPXN1, a gene closely associated with oil accumulation. Through phylogenetic analysis, we hypothesized that GhPXN1 in G. hirsutum might have been introgressed from G. arboreum. Overexpression of the GhPXN1 gene in tobacco leaf suggested a significant reduction in oil content compared to the empty-vector transformants. Furthermore, ten other crucial oil candidate genes identified in this study were also validated using quantitative real-time PCR (qRT-PCR). CONCLUSIONS: Overall, this study enhances our comprehension of the molecular mechanisms underlying cottonseed oil accumulation.

Endocytosis-mediated entry of a caterpillar effector into plants is countered by Jasmonate.

Insects and pathogens release effectors into plant cells to weaken the host defense or immune response. While the imports of some bacterial and fungal effectors into plants have been previously characterized, the mechanisms of how caterpillar effectors enter plant cells remain a mystery. Using live cell imaging and real-time protein tracking, we show that HARP1, an effector from the oral secretions of cotton bollworm (Helicoverpa armigera), enters plant cells via protein-mediated endocytosis. The entry of HARP1 into a plant cell depends on its interaction with vesicle trafficking components including CTL1, PATL2, and TET8. The plant defense hormone jasmonate (JA) restricts HARP1 import by inhibiting endocytosis and HARP1 loading into endosomes. Combined with the previous report that HARP1 inhibits JA signaling output in host plants, it unveils that the effector and JA establish a defense and counter-defense loop reflecting the robust arms race between plants and insects.

Effects of Tai Chi on depression of middle-aged and older adults: an updated systematic review and meta-analysis.

AIM: The objective of this study was to evaluate the efficacy of Tai Chi, a mind-body movement therapy originating from China, on depression in middle-aged and older adults. METHODS: A systematic search was conducted in seven databases (Embase, Cochrane, Medline, Wanfang, SinoMed, Weipu date, CNKI) for Randomized Controlled Trials (RCTs) published until Apr 16, 2023. The quality assessment, heterogeneity analysis, subgroup analysis, and sensitivity analysis of 12 RCTs selected from the literature were performed. Meta-analyses were conducted using RevMan 5.4 software. RESULTS: The study included 12 trials comprising 731 participants that met the inclusion criteria. The findings revealed that Tai Chi significantly improved depression in middle-aged and older adults [SMD = -1.21, 95% CI (-1.59, -0.83), I2 = 87.6%, P < 0.001]. Subgroup analysis revealed that the number of exercise weeks within the specified range, the total duration of exercise, and Tai Chi maneuvers had the greatest benefits on depression in middle-aged and elderly people. The results demonstrated that interventions lasting more than 24 weeks were more effective [SMD = -1.66, 95% CI (-2.28, -1.04), P < 0.05] than those lasting only 12 weeks [SMD = -0.73, 95% CI (-1.08, -0.38), P < 0.05]. The effect size was more significant when the total duration of the intervention was more than 2400 min [SMD = -1.31, 95% CI (-1.71, -0.92), P < 0.001], and when the 24-style Tai Chi exercise was selected [SMD = -1.06, 95% CI (-1.37, -0.75), P < 0.001], the difference was also statistically significant. Funnel plots combined with sensitivity analyses, Begg's and Egger's tests indicated no publication bias. CONCLUSION: The study suggests that Tai Chi can be an alternative therapy for reducing depression in middle-aged and older adults. It is recommended to prolong the Tai Chi exercise period to more than 24 weeks, with a total exercise duration of more than 2400 min, and 24-style Tai Chi should be selected to achieve the best therapeutic effect in middle-aged and older adults with depression. It should be noted that there may be lower-quality studies in the RCT literature analyzed, which may limit the general applicability and credibility of the conclusions.

Phenolics and Terpenoids Profiling in Diverse Loquat Fruit Varieties and Systematic Assessment of Their Mitigation of Alcohol-Induced Oxidative Stress.

To compare and investigate the phenolic compounds in the peel and flesh of loquat (Eriobotrya japonica) and evaluate their ability to protect against alcohol-induced liver oxidative stress, we employed a combination of ultra-performance liquid chromatography (UPLC) and high-resolution mass spectrometry (HRMS) to qualitatively and quantitatively analyze 22 phenolics and 2 terpenoid compounds in loquat peel and flesh extracts (extraction with 95% ethanol). Among these, six compounds were identified for the first time in loquat, revealing distinct distribution patterns based on variety and tissue. Various chemical models, such as DPPH, FRAP, ORAC, and ABTS, were used to assess free radical scavenging and metal ion reduction capabilities. The results indicate that peel extracts exhibited higher antioxidant capacity compared with flesh extracts. Using a normal mouse liver cell line, AML-12, we explored the protective effects of loquat extracts and individual compounds against ethanol-induced oxidative stress. The findings demonstrate the enhanced cell viability and the induction of antioxidant enzyme activity through the modulation of Nrf2 and Keap1 gene expression. In a C57/BL6 mouse model of alcohol-induced liver damage, loquat extract was found to alleviate liver injury induced by alcohol. The restoration of perturbed serum liver health indicators underscored the efficacy of loquat extract in reclaiming equilibrium. The culmination of these findings significantly bolsters the foundational knowledge necessary to explore the utilization of loquat fruit extract in the creation of health-focused products.

Identification of New Antiseizure Medication Candidates in Preclinical Animal Studies.

Epilepsy is a multifactorial neurologic disease that often leads to many devastating disabilities and an enormous burden on the healthcare system. Until now, drug-resistant epilepsy has presented a major challenge for approximately 30% of the epileptic population. The present article summarizes the validated rodent models of seizures employed in pharmacological researches and comprehensively reviews updated advances of novel antiseizure candidates in the preclinical phase. Newly discovered compounds that demonstrate antiseizure efficacy in preclinical trials will be discussed in the review. It is inspiring that several candidates exert promising antiseizure activities in drug-resistant seizure models. The representative compounds consist of derivatives of hybrid compounds that integrate multiple approved antiseizure medications, novel positive allosteric modulators targeting subtype-selective γ-Aminobutyric acid type A receptors, and a derivative of cinnamamide. Although the precise molecular mechanism, pharmacokinetic properties, and safety are not yet fully clear in every novel antiseizure candidate, the adapted approaches to design novel antiseizure medications provide new insights to overcome drug-resistant epilepsy.

Associations between the inflammatory potential of diets with adherence to plant-based dietary patterns and the risk of new-onset cardiometabolic diseases in Chinese adults: findings from a nation-wide prospective cohort study.

Aims: convincing evidence is still limited for the validation of associations between the inflammatory potential of diets, based on the dietary inflammatory index (DII), and cardiometabolic outcomes. We aimed to investigate the associations between the DII with adherence to plant-based dietary patterns and the risk of new-onset cardiometabolic diseases (CMDs), including stroke, type 2 diabetes mellitus (T2DM) and myocardial infarction (MI). Methods: adults (N = 14 652) from the China Health and Nutrition Survey (1997-2015) were included in the current analysis. Dietary intake data were collected using a combination of 3 day consecutive 24 h dietary recalls and the food weighing method. The DII was calculated with established and validated methods. CMDs were identified using validated self-reported questionnaires. The Cox proportional hazard regression model was used for statistical analysis. Results: during a mean follow-up of 10 years, a total of 404 new-onset stroke, 1051 new-onset T2DM and 280 new-onset MI cases were identified. Lower PDI, hPDI, ERD, WISH and PHDI scores and higher uPDI scores were associated with higher DII scores (all P-trend < 0. 0001). A pro-inflammatory diet, as reflected by relatively higher DII scores, was positively associated with an increased risk of stroke (Q5 vs. Q1: HR = 1.90; 95% CI: 1.26-2.88; P-trend = 0.0006), T2DM (Q5 vs. Q1: HR = 2.08; 95% CI: 1.61-2.69; P-trend < 0.0001) and MI (Q5 vs. Q1: HR = 1.70; 95% CI: 1.04-2.76; P-trend = 0.0114) in the entire cohort. Sex and BMI significantly modified the association between the DII and the risk of T2DM, and sex significantly modified the association between the DII and the risk of MI. Conclusions: lower adherence to healthy and sustainable plant-based dietary patterns and higher adherence to unhealthy plant-based dietary patterns were associated with higher DII scores. With the use of the DII, we reported long-term positive associations between a pro-inflammatory diet and an increased risk of new-onset stroke, T2DM and MI in Chinese adults who were free from CMDs and cancer at the baseline. These findings provided evidence for the validation of associations between the DII and cardiometabolic health, and contributed to the current literature suggesting careful evaluations of whether the DII should be incorporated into dietary guidelines and utilized as an effective tool for improving the diet quality and CMD prevention in the Chinese population.