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Abstract Objective N‐methyl‐D‐aspartate receptors are glutamate‐gated ion channels that play a crucial role in brain function. Numerous inherited or de novo variants in the GRIN2A gene, encoding the GluN2A subunit of the receptor, have been identified in patients with epilepsy. In addition, it is worth noting that GRIN2A variants exhibit a strong correlation with epilepsy‐aphasia syndromes, a group of age‐dependent epileptic, cognitive, and language disorders with a characteristic electroencephalographic pattern. Methods Whole exome sequencing was conducted in enrolled patients with epilepsy‐aphasia syndromes, and GRIN2A variants were screened. The conservation of substituted residues, conformational changes of mutant subunits, and in silico predictions of pathogenicity were thoroughly assessed in our study. Functional alterations of the variants were examined using whole‐cell voltage‐clamp current recordings while the relative surface expression levels of subunit proteins were assessed via immunofluorescence assays. A summary of previously published GRIN2A missense variants was conducted to investigate the genotypic‐phenotypic‐functional correlations. Results Two missense GRIN2A variants (c. 2482A >G/p. M828V, c. 2627 T >C/p. I876T) were identified, which are located in the transmembrane helix M4 and C‐terminus domain of the GluN2A subunit, respectively. Both variants exhibited reduced current density of NMDARs and surface/total expression levels of GluN2A subunits, while M828V showed a decreased extent of desensitization as well. A further summary of the previously reported GRIN2A variants demonstrated that more variable phenotypes were observed for variants situated in the C‐terminus domain or those with loss‐of‐function effects. Significance Our study expands the phenotypic and functional range of GRIN2A‐related disorders. In order to optimally establish the domain‐function‐phenotype correlations in GRIN2A variants, it is imperative to gather a more extensive set of clinical and functional data. Plain Language Summary This study has identified two genetic variants of the GRIN2A gene in patients with epilepsy‐aphasia syndrome. We assess the variants' harmfulness through a variety of functional experiments, including evaluating the expression level of the mutated protein and the resulting changes in electrophysiological activities. Also, we reviewed previously published papers about GRIN2A variants in epilepsy to learn more about the correlations between their locations, functional changes, and clinical manifestations.

Abstract There are no studies discussing the significance of neutrophil-to-lymphocyte ratio (NLR), neutrophil-percentage-to-albumin ratio (NPAR), and systemic immune-inflammation index (SII) in predicting poor prognosis in patients with metabolic dysfunction associated steatotic liver disease (MASLD); this study aimed to investigate the relationship between these three inflammatory markers and all-cause mortality and cardiovascular disease (CVD) mortality in patients with MASLD. Survival data for 3970 participants were obtained from National Death Index (NDI) records associated with the National Health and Nutrition Examination Survey (NHANES) dataset, the associations of NPAR, NLR, and SII with all-cause and CVD mortality were analyzed using multivariate COX regression modeling, restricted cubic spline (RCS) was used to explore nonlinear relationships and to determine the inflection point, regrouping was done according to the nonlinear inflection point, using multivariate COX regression modeling, subgroup analysis, and the Kaplan-Meier survival curves to evaluate differences in risk of death between the two groups. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to assess the predictive efficacy of NPAR, NLR, and SII on survival outcomes. Multivariate COX regression and RCS analyses revealed a positive linear correlation between NLR and all-cause and CVD mortality, whereas a nonlinear relationship was found between NPAR and SII and all-cause and CVD mortality. Further reclassified into two groups according to the inflection point, multivariate COX regression analyses showed a significant difference in the risk of death between the two NPAR groups (HR 1.37, 95% CI = (1.01, 1.86) for all-cause mortality and HR 2.03, 95% CI = (1.24, 3.32) for CVD mortality ) and no difference in the risk of death between the two SII groups (HR 1.11, 95% CI = (0.87, 1.42) for all-cause mortality and HR 1.35, 95% CI = (0.86, 2.12) for CVD mortality), and Kaplan-Meier survival curves showed that both all-cause and CVD mortality rates were higher in patients with MASLD above the NPAR inflection point (log-rank P 0.05). Also, COPD subgroups had a significant effect on the correlation between high levels of NPAR and CVD mortality (P interaction < 0.05). Time-dependent ROC show the predictive value of NPAR, NLR, and SII for all-cause and CVD mortality in MASLD patients. The correlation between NPAR and mortality was nonlinear, and NLR was linearly and positively correlated with mortality, Measuring NPAR and NLR may be useful in assessing risk and predicting prognosis in populations of patients with MASLD.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition and a leading cause of mortality, with acute exacerbations (AECOPD) significantly complicating its management and prognosis. Despite the development of various prognostic prediction models for patients with AECOPD, their performance and clinical applicability remain unclear, necessitating a systematic review to evaluate these models and provide guidance for their future improvement and clinical use. Method PubMed, Web of Science, CINAHL, Scopus, EMBASE, and Medline were searched for studies published from their inception until February 5, 2024. Data extraction and evaluation were conducted using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). The Prediction model Risk Of Bias Assessment Tool (PROBAST) was employed to assess the risk of bias and applicability of the models. Results After deduplication and screening 5942 retrieved articles, 46 studies comprising 53 models were included. Of these, 17 (37.0%) studies developed from studies conducted in China. All models were based on cohort studies. Mortality was the predicted outcome in 27 (50.9%) models. Logistic regression was used in 41 (77.4%) models, while machine learning methods were employed in 9 (17.0%) models. The median (minimum, maximum) sample size for model development was 672 (106, 150,035). The median (minimum, maximum) number of predictors per model was 5 (2, 42). Frequently used predictors included age (n = 28), dyspnea severity scores (n = 12), and PaCO2 (n = 11). The pooled AUC was 0.80 for mortality prediction models and 0.84 for hospitalization-related outcomes. 52 models have a high overall risk of bias, and all models were judged to have low concern regarding applicability. Major sources of bias included insufficient sample sizes (83.0%), reliance on univariate analysis for predictor selection (73.6%), inappropriate internal and external validation methods (54.7%), inappropriate inclusion and exclusion criteria for study subjects (50.9%) and so on. The only model with low bias was the PEARL score. Conclusion Current prognostic risk prediction models for patients with AECOPD generally exhibit high bias. Future efforts should standardize model development and validation methods, and develop widely usable clinical models.

Abstract Ermiao wan (EMW) is a classical traditional Chinese medicine formula, with two modified versions including Sanmiao wan (SMW) and Simiao wan (FMW). These Ermiao wan categorized formulas (ECFs) are traditionally used to treat gouty arthritis and hyperuricemia. However, their potential benefits and mechanisms on diabetes remain to be explored. This study aims to investigate the overall effects and biological differences of ECFs in high fat diet (HFD)-fed mice based on network pharmacology and transcriptomics. ECFs significantly reduced body weight, improved oral glucose tolerance, decreased fat accumulation, and lowered serum insulin and inflammatory cytokine levels in HFD-fed mice. FMW had better efficacy than EMW and SMW. Network pharmacology analysis revealed that ECFs targeted functional modules associated with chronic inflammation, lipid metabolism, and glucose metabolism. Transcriptome results also showed ECFs could inhibit genes associated with inflammation and upregulated some genes in lipid metabolism. Comprehensive analysis and QPCR verification indicated the beneficial effects of ECFs on diabetes might be attributed to the regulation of Ddit3, Ccl2, Esr1, and Cyp7a1. This study provides a theoretical basis for the clinical use of ECFs.

Abstract Objective Early identification of modifiable risk factors is crucial for the prevention of constipation. This study systematically investigated the relationship between genetically predicted modifiable risk factors and constipation. Methods The inverse variance weighting (IVW) method was employed as the primary analytical approach. For similar exposure indicators, the multivariate Mendelian randomization (MVMR) method was used to adjust for potential biases in univariate MR analysis. The robustness of the results was further evaluated using the MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis. Bonferroni correction was applied to reduce the false positive rate in the results. Results The IVW analysis indicated a significant causal association between genetically predicted gastroesophageal reflux disease [OR (95% CI) = 1.192 (1.079–1.315), P = 0.0005], atorvastatin use [OR (95% CI) = 16.995 (3.327–86.816), P = 0.0007], and constipation. Additionally, there was a potential causal association between education level [OR (95% CI) = 0.859 (0.767–0.964), P = 0.009], major depressive disorder [OR (95% CI) = 1.206 (1.041–1.399), P = 0.013], hypothyroidism [OR (95% CI) = 2.299 (1.327–3.985), P = 0.003], and aspirin use [OR (95% CI) = 4.872 (1.174–20.221), P = 0.029] with constipation. No causal associations were found for the other included indicators. Sensitivity analysis demonstrated the absence of evidence for heterogeneity and pleiotropy in any positive results. Conclusion This study identified several risk factors that could be targeted for the prevention of constipation, offering valuable insights for public health policies.

Objectives: Mycobacterium abscessus complex (MABC) is the most common rapidly growing Mycobacterium species in structural pulmonary diseases and can be life-threatening. This study aimed to assess the clinical characteristics and drug-susceptibility statuses of different M. abscessus (MAB) subspecies in the Zhejiang Province. Methods: DNA sequencing was used to differentiate clinical MABC subspecies isolates. The Clinical and Laboratory Standards Institute guidelines were used to determine in vitro susceptibility of imipenem-relebactam (IMP-REL), omadacycline, and other conventional antibiotics. Patient clinical characteristics were collected and analysed. Results: In total, 139 M. abscessus, 39 Mycobacterium massiliense, and 1 Mycobacterium bolletii isolates were collected, accounting for 77.7%, 21.8%, and 0.5% of the MABC isolates, respectively. Patients with M. abscessus pulmonary disease (M.ab-PD) had higher proportions of older adults, tuberculosis history, chronic pulmonary disease, and malignancy than those with M. massiliense pulmonary disease (M.ma-PD). Patients with M.ab-PD had higher rates of bilateral middle- and lower-lobe involvement than patients with M.ma-PD. Both subspecies showed high resistance rates to doxycycline and moxifloxacin, and clarithromycin-induced resistance was more common in M.ab than in M.ma. IMP-REL resulted in a twofold reduction in the minimum inhibitory concentration (MIC) value compared with imipenem alone among MAB; furthermore, the MIC was lower in M.ab than in M.ma. Omadacycline and tigecycline had comparable in vitro susceptibility, and the MIC showed no statistically significant difference between M.ab and M.ma. Conclusions: M.ab is the most prevalent MABC subspecies in the Zhejiang Province. Patients with M.ab-PD have complex underlying diseases and broader lobar lesions. IMP-REL and omadacycline are promising antibiotics for MABC infection treatment.

Abstract RNA-binding proteins (RBPs) play critical roles in genome regulation. In this study, we explored the latent function of KPNA2, which is an essential member of the RBP family, in the regulation of alternative splicing (AS) in gastric cancer (GC). We analyzed the role of KPNA2 in regulating differential expression and AS via RNA sequencing (RNA-seq) and improved RNA immunoprecipitation sequencing (iRIP-seq). Clinical specimens were used to analyze the associations between KPNA2 expression and clinicopathological characteristics. CCK8 assays, transwell assays and wound healing assays were performed to explore the effect of KPNA2/WDR62 on GC cell progression. KPNA2 was shown to be highly expressed in GC cells and tissues and associated with lymph node metastases. KPNA2 promoted the proliferation, migration and invasion of GC cells and primarily regulated exon skipping, alternative 3's splice sites (A3SSs), alternative 5' splice sites (A5SSs), and cassette exons. We further revealed that KPNA2 participated in biological processes related to cell proliferation, and the immune response in GC via the regulation of transcription. In addition, KPNA2 preferentially bound to intron regions. Notably, KPNA2 regulated the A3SS AS mode of WDR62, and upregulation of WDR62 reversed the KPNA2 downregulation-induced inhibition of GC cell proliferation, migration and invasion. Finally, we discovered that the AS of immune-related molecules could be regulated by KPNA2. Overall, our results demonstrated for the first time that KPNA2 functions as an oncogenic splicing factor in GC that regulated the AS and differential expression of GC-related genes, and KPNA2 may be a potential target for GC treatment.

Collagen, as a commercial functional protein, is widely applied in food, cosmetics, biomedicine and other industries, and swim bladder is regarded as an ideal source of raw materials due to its rich collagen content. Chu’s croaker (Nibea coibor), as an economical fish that can produce high-grade swim bladder, is popularly farmed, however, its high fishmeal demand limits the development of the feed industry. Therefore, it is worth thinking about how to reduce the use of fish meal without affecting the swim bladder quality. Given that, an 8-week feeding trial was conducted to investigate the effects of fish meal partially replaced (0.0%, 5.0%, 10.0%, 15.0%, 20.0%) with composite proteins (CPs, consisted of corn protein meal and hydrolyzed feather meal) on growth, antioxidant capacity and swim bladder quality (texture and collagen deposition) of chu’s croaker. Results showed that although growth performance decrease with the increase of CPs’ replacement level, it did not compromise the swim bladder quality. Specifically, 5% - 10% CPs did not affect the growth significantly, but can improve antioxidant capacity, protein content, collagen synthesis and texture quality of swim bladder. The enhancement of swim bladder texture, including hardness, chewiness, springiness, and adhesiveness may be caused by changes in the expression of related genes, such as colga1t1, col12a1, cyp27a1, etc. These results indicated that appropriate fish meal replaced by CPs could be applied during aquaculture practice after comprehensive consideration of feed cost, growth rate and quality of swim bladder. This study provides support for the development of cost-effective feed formulations that improve the sustainability and economic viability of chu’s croaker culture.

Artificial intelligence (AI) technology is deeply changing our lives and provides impetus for improving production and living efficiency as an important emerging tool. Digitalization and intelligent development have also become the development direction of the sports industry, bringing new requirements to the transformation of physical education (PE) and the improvement of the quality of PE teachers. PE is an important part of the public health system, and AI can deeply participate in the formulation of teaching strategies, the tracking of teaching processes and the evaluation of teaching results, effectively improving the quality of teaching. Research on the application of AI technology in PE has been carried out. This paper comprehensively reviews the existing research and conducts a comprehensive analysis of the research progress and status. The potential application areas of AI in PE are discussed to better promote the intelligent and digital upgrading of PE. We found that the research on the application of AI in PE is still in its early stages, and the research content needs to be strengthened in terms of breadth and depth. Furthermore, this paper analyzes the challenges faced by PE teacher development and training in the context of educational transformation in the era of AI, and explores the necessary skills and knowledge related to AI technology that future PE teachers should master in order to effectively achieve the improvement of teaching level and the sustainable development of public health system. The review of this paper provides valuable guidance for educators and policymakers to formulate high-quality teacher development and training mechanisms, and provides a new reference for the application and development of AI in sports.

Taste quality is one of the most important indicators for assessing the quality of rice. However, there has been a lack of systematic studies investigating the impact factors of taste quality. In this study, chromosomal segment substitution lines (CSSLs) with notable differences in physicochemical properties were obtained by screening the CSSL population. A correlation analysis between the physicochemical properties and the taste qualities of rice revealed that amylose and protein content are significantly negatively correlated with the taste value of both freshly cooked and rehydrated instant rice. The alkali spreading value (ASV) had limited impact on the taste value of rice, but low-ASV rice is more resistant to cooking. Grain chalkiness played a critical role in maintaining the integrity of freshly cooked rice and instant rice grains after rehydration. In summary, our study provides crucial insights and guidance for rice breeding, with the goal of developing excellent quality and enhancing the processing of instant rice.

BackgroundEpilepsy, a common neurological disorder, has been increasingly associated with neuroinflammation, especially microglia activation. To gain insights into the research trends and patterns in this intersection, we conducted a bibliometric analysis of studies published between 2005 and 2024. Using the Web of Science Core Collection, we identified 1,229 relevant articles and reviews, focusing on the relationship between epilepsy and microglia.MethodsWe employed the Bibliometrix R package and VOSviewer to analyze the data. Our search strategy combined epilepsy-related terms with microglia and microglial cell keywords. The analysis encompassed publication trends, country and institutional contributions, journal sources, authors, keywords, and thematic evolution.ResultsThe number of publications has steadily increased, particularly after 2019, indicating growing research interest. The United States, China, and Germany emerged as the most productive countries, with extensive collaboration between China and the United States. Epilepsia and Journal of Neuroinflammation were the most influential journals. Aronica E, Vezzani A, and Engel T were the most prolific authors. Thematic analysis revealed clusters focused on temporal lobe epilepsy, epilepsy-related disorders, and microglia activation. Over the past several years, research has shifted from fundamental brain function studies to in-vivo investigations of specific molecular mechanisms. The CSTB (−) mouse model and NF-κB signaling pathway both merit further in-depth investigation.ConclusionIn conclusion, this bibliometric study reveals a surge in epilepsy-microglia research, led by key countries, journals, and researchers. Temporal lobe epilepsy, epilepsy-related disorders, and microglia activation are focal themes. Future directions include exploring microglia activation mechanisms, utilizing animal models, and interdisciplinary approaches.

In future regenerative medicine, far-infrared radiation (FIR) may be an essential component of optical therapy. Many studies have confirmed or validated the efficacy and safety of FIR in various diseases, benefiting from new insights into FIR mechanisms and the excellent performance of many applications. However, the lack of consensus on the biological effects and therapeutic parameters of FIR limits its practical applications in the clinic. In this review, the definition, characteristics, and underlying principles of the FIR are systematically illustrated. We outline the therapeutic parameters of FIR, including the wavelength range, power density, irradiation time, and distance. In addition, the biological effects, potential molecular mechanisms, and preclinical and clinical applications of FIR are discussed. Furthermore, the future development and applications of FIR are described in this review. By applying optimal therapeutic parameters, FIR can influence various cells, animal models, and patients, eliciting diverse underlying mechanisms and offering therapeutic potential for many diseases. FIR could represent a superior alternative with broad prospects for application in future regenerative medicine.

Abstract Peptides and proteins encoded by noncanonical open reading frames (ORFs) of circRNAs have recently been recognized to play important roles in disease progression, but the biological functions and mechanisms of these peptides and proteins are largely unknown. Here, we identified a potential coding circular RNA, circTRIM1, that was upregulated in doxorubicin-resistant TNBC cells by intersecting transcriptome and translatome RNA-seq data, and its expression was correlated with clinicopathological characteristics and poor prognosis in patients with TNBC. CircTRIM1 possesses a functional IRES element along with an 810 nt ORF that can be translated into a novel endogenously expressed protein termed TRIM1-269aa. Functionally, we demonstrated that TRIM1-269aa, which is involved in the biological functions of circTRIM1, promoted chemoresistance and metastasis in TNBC cells both in vitro and in vivo. In addition, we found that TRIM1-269aa can be packaged into exosomes and transmitted between TNBC cells. Mechanistically, TRIM1-269aa enhanced the interaction between MARCKS and calmodulin, thus promoting the calmodulin-dependent translocation of MARCKS, which further initiated the activation of the PI3K/AKT/mTOR pathway. Overall, circTRIM1, which encodes TRIM1-269aa, promoted TNBC chemoresistance and metastasis by enhancing MARCKS translocation and PI3K/AKT/mTOR activation. Our investigation has yielded novel insights into the roles of protein-coding circRNAs and supported circTRIM1/TRIM1-269aa as a novel promising prognostic and therapeutic target for patients with TNBC.

Abstract Presurgical evaluation is still challenging for MRI‐negative epilepsy patients. As non‐invasive modalities are the easiest acceptable and economic methods in determining the epileptogenic zone, we analyzed the localization value of common non‐invasive methods in MRI‐negative epilepsy patients. In this study, we included epilepsy patients undergoing presurgical evaluation with presurgical negative MRI. MRI post‐processing was performed using a Morphometric Analysis Program (MAP) on T1‐weighted volumetric MRI. The relationship between MAP, magnetoencephalography (MEG), scalp electroencephalogram (EEG), and seizure outcomes was analyzed to figure out the localization value of different non‐invasive methods. Eighty‐six patients were included in this study. Complete resection of the MAP‐positive regions or the MEG‐positive regions was positively associated with seizure freedom (p = 0.028 and 0.007, respectively). When an area is co‐localized by MAP and MEG, the resection of the area was significantly associated with seizure freedom (p = 0.006). However, neither the EEG lateralization nor the EEG localization showed statistical association with the surgical outcome (p = 0.683 and 0.505, respectively). In conclusion, scalp EEG had a limited role in presurgical localization and predicting seizure outcome, combining MAP and MEG results can significantly improve the localization of epileptogenic lesions and have a positive association with seizure‐free outcome. Plain Language Summary Due to the lack of obvious structure abnormalities on neuroimaging examinations, the identification of epilepsy lesions in MRI‐negative epilepsy patients can be difficult. In this study, we intended to use non‐invasive examinations to explore the potential epileptic lesions in MRI‐negative epilepsy patients and to determine the results accuracy by comparing the neuroimaging results with the epilepsy surgery outcomes. A total of 86 epilepsy patients without obvious structure lesions on MRI were included, and we found that the combinations of different non‐invasive examinations and neuroimaging post‐processing methods are significantly associated with the seizure freedom results of epilepsy surgery.

Abstract Triple‐negative breast cancer (TNBC) is the most malignant subtype of breast cancer. TP53, which has a mutation rate of ≈70%–80% in TNBC patients, plays oncogenic roles when mutated. However, whether circRNAs can exert their effects on TNBC through regulating mutant TP53 has not been well evaluated. In this study, circCFL1, which is highly expressed in TNBC cells and tissues and has prognostic potential is identified. Functionally, circCFL1 promoted the proliferation, metastasis and stemness of TNBC cells. Mechanistically, circCFL1 acted as a scaffold to enhance the interaction between HDAC1 and c‐Myc, further promoting the stability of c‐Myc via deacetylation‐mediated inhibition of K48‐linked ubiquitylation. Stably expressed c‐Myc further enhanced the expression of mutp53 in TNBC cells with TP53 mutations by directly binding to the promoter of TP53, which promoted the stemness of TNBC cells via activation of the p‐AKT/WIP/YAP/TAZ pathway. Moreover, circCFL1 can facilitate the immune escape of TNBC cells by promoting the expression of PD‐L1 and suppressing the antitumor immunity of CD8+ T cells. In conclusion, the results revealed that circCFL1 plays an oncogenic role by promoting the HDAC1/c‐Myc/mutp53 axis, which can serve as a potential diagnostic biomarker and therapeutic target for TNBC patients with TP53 mutations.

Abstract Objective The right posterior parietal cortex is the core brain region of emotional processing and executive control network in the human brain, and the function of the right posterior parietal cortex is decreased in patients with major depressive disorder. This study aims to preliminarily investigate whether the excitation of the right posterior parietal cortex by transcranial direct current stimulation (tDCS) could improve their clinical symptoms. Methods In this study, 12 patients with major depressive disorder were given tDCS treatment at Xuanwu Hospital of Capital Medical University and the First Hospital of Hebei Medical University. The stimulating electrode (anode) was placed on the patients’ right parietal cortex, whereas the reference electrode (cathode) was placed on the patients’ left mastoid. The stimulation intensity was set as 2.0 mA. The patients with depressive disorder were treated for 20 min at a time twice a day for 14 consecutive days. The severity of the clinical symptoms was evaluated using the Hamilton Depression Rating Scale‐17 (HDRS‐17) and the Hamilton Anxiety Rating Scale (HARS) at before and right after treatment. Results The HDRS‐17 scores of patients with depressive disorder decreased significantly following the tDCS treatment compared with those before treatment (p

Background and objectiveExtracellular adenosine (eAdo) bridges tumor metabolism and immune regulation. CD39-CD73-eAdo/A2aR axis regulates tumor microenvironment (TME) and immunotherapy response. In the era of immunotherapy, exploring the impact of the CD39-CD73-eAdo/A2aR axis on TME and developing targeted therapeutic drugs to enhance the efficacy of immunotherapy are the current research hotspots. This study summarizes and explores the research trends and hotspots of the adenosine axis in the field of TME to provide ideas for further in-depth research.MethodsLiterature information was obtained from the Web of Science core collection database. The VOS viewer and the bibliometric tool based on R were used to quantify and identify cooperation information and individual influence by analyzing the detailed information of the global annual publication volume, country/region and institution distribution, article authors and co-cited authors, and journal distribution of these articles. At the same time, the distribution of author keywords and the co-occurrence of author keywords, highly cited articles, and highly co-cited references of CD39-CD73-eAdo/A2aR in the field of TME were analyzed to determine research hotspots and trends.Result1,721 articles published in the past ten years were included in this study. Through bibliometric analysis, we found that (1) 69 countries and regions explored the effect of the CD39-CD73-eAdo/A2aR on TME, and the research was generally on the rise. Researchers in the United States dominated research in this area, with the highest total citation rate. China had the most significant number of publications. (2) Harvard University has published the most articles in this field. (3) 12,065 authors contributed to the publication of papers in this field, of which 23 published at least eight papers. STAGG J had significant academic influence, with 24 published articles and 2,776 citations. Co-cited authors can be clustered into three categories. Stagg J, Allard B, Ohta A, and Antonioli, L occupied a central position in the network. (4) 579 scholarly journals have published articles in this field. The journal FRONTIERS IN IMMUNOLOGY published the most significant number of papers, with 97 articles and a total of 2,317 citations, and the number of publications increased year by year. (5) “The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets” was the most frequently local cited article (163 times). The “A2A adenosine receptor protects tumors from antitumor T cells” was the most co-cited reference (224 times). (6) Through the analysis of author keywords, we found that the relationship between adenosine and immunotherapy was a core concept for many researchers in this field. Breast cancer, melanoma, colorectal cancer, ovarian cancer, glioblastoma, pancreatic cancer, hepatocellular carcinoma, and lung cancer were the most frequent cancer types in adenosine-related tumor studies. Immunotherapy, immunosuppression, immune checkpoint, and immune checkpoint inhibitors were the hot keywords in the research, reflecting the importance of the adenosine metabolic pathway in tumor immunotherapy. The keywords such as Immunogenic cell death, T cells, Sting, regulatory T cells, innate immunity, and immune infiltration demonstrated the pathways by which adenosine affected the TME. The famous author keywords in recent years have been immunotherapy, immunogenic cell death, inflammation, lung cancer, and gastric cancer.ConclusionThe effect of CD39-CD73-eAdo/A2aR on the infiltration and function of various immune cells in TME, tumor immunotherapy response, and patient prognosis has attracted the attention of researchers from many countries/regions. American scholars still dominate the research in this field, but Chinese scholars produce the most research results. The journal FRONTIERS IN IMMUNOLOGY has published the wealthiest research in the field. Stagg J was a highly influential researcher in this field. Further exploration of targeted inhibition of CD39-CD73-eAdo/A2aR alone or in combination with other immunotherapy, radiotherapy, and chemotherapy in treating various cancer types and developing effective clinical therapeutic drugs are continuous research hotspots in this field.

As two spatial geographic units that are both independent of each other and closely linked, the land and sea have complex spatial interactions. Therefore, China implements the land-sea coordination policy (LSC) needs to be approached from a more macroscopic, systematic and comprehensive perspective. Based on the interregional externality theory, this study takes the land-sea coordination policy of China as an example, and focuses on the interaction process and manifestation between land and sea, and then explores the connotation and realization path of LSC. Firstly, we delineated the spatial unit and analyzed the land-sea interactions (LSI) using Vensim software. Secondly, the characteristics and manifestations of LSI are summarized from the perspective of interregional externalities. Finally, this study elucidates the foundational concept of implementing LSC and further propose actionable pathways for promoting land and sea development in a coordinated way, aimed at offering supportive decision-making insights for achieving LSC within the broader framework of China’s territorial spatial planning. Initiating LSC implementation involves strategies such as source control, process management, and interaction interface optimization. Deepening LSC effectiveness entails strengthening positive interregional externalities while mitigating negative interregional externalities.

ObjectiveThe study aims to identify the drugs associated with drug withdrawal syndrome in the Food and Drug Administration Adverse Event Reporting System (FAERS) and estimate their risks of causing withdrawal syndrome.MethodsAll the data were collected from FAERS from the first quarter of 2004 to the third quarter of 2023. Disproportionality analyses of odds ratio (ROR) and proportional reported ratio were conducted to identify potential adverse effects signal of drug withdrawal syndrome.ResultsA total of 94,370 reports related to withdrawal syndrome from the data. The top 50 drugs with most frequency reported were analyzed, and 29 exhibited a positive signal based on the number of reports. The top three categories of drugs with positive signals included opioids, antidepressant drugs and antianxiety drugs. Other classifications included opioid antagonist, muscle relaxant, antiepileptic drugs, analgesics, hypnotic sedative drugs and antipsychotic drugs.ConclusionOur analysis of FAERS data yielded a comprehensive list of drugs associated with withdrawal syndrome. This information is vital for healthcare professionals, including doctors and pharmacists, as it aids in better recognition and management of withdrawal symptoms in patients undergoing treatment with these medications.

Molecular-assisted breeding is an effective way to improve targeted agronomic traits. dep1 (dense and erect panicle 1) is a pleiotropic gene that regulates yield, quality, disease resistance, and stress tolerance, traits that are of great value in rice (Oryza sativa L.) breeding. In this study, a colorimetric LAMP (loop-mediated isothermal amplification) assay was developed for the detection of the dep1 allele and tested for the screening and selection of the heavy-panicle hybrid rice elite restorer line SHUHUI498, modified with the allele. InDel (Insertion and Deletion) primers (DEP1_F and DEP1_R) and LAMP primers (F3, B3, FIP, and BIP) for genotyping were designed using the Primer3 Plus (version 3.3.0) and PrimerExplore (version 5) software. Our results showed that both InDel and LAMP markers could be used for accurate genotyping. After incubation at a constant temperature of 65 °C for 60 min with hydroxynaphthol blue (HNB) as a color indicator, the color of the LAMP assay containing the dep1 allele changed to sky blue. The SHUHUI498 rice line that was detected in our LAMP assay displayed phenotypes consistent with the dep1 allele such as having a more compact plant architecture, straight stems and leaves, and a significant increase in the number of effective panicles and spikelets, demonstrating the effectiveness of our method in screening for the dep1 allele in rice breeding.

Summary: The 2022 mpox outbreak led the World Health Organization (WHO) to declare it a public health emergency of international concern (PHEIC). There is a need to develop more effective and safer mpox virus (MPXV)-specific vaccines in response to the mpox epidemic. The mRNA vaccine is a promising platform to protect against MPXV infection. In this study, we construct two bivalent MPXV mRNA vaccines, designated LBA (B6R-A29L) and LAM (A35R-M1R), and a quadrivalent mRNA vaccine, LBAAM (B6R-A35R-A29L-M1R). The immunogenicity and protective efficacy of these vaccines alone or in combination were evaluated in a lethal mouse model. All mRNA vaccine candidates could elicit potential antigen-specific humoral and cellular immune responses and provide protection against vaccinia virus (VACV) infection. The protective effect of the combination of two bivalent mRNA vaccines and the quadrivalent vaccine was superior to that of the individual bivalent mRNA vaccine. Our study provides valuable insights for the development of more efficient and safer mRNA vaccines against mpox.

Initial indications propose that repetitive transcranial magnetic stimulation (rTMS) could mitigate clinical manifestations in patients with autism spectrum disorder (ASD). Nevertheless, the precise mechanisms responsible for these therapeutic and behavioral outcomes remain elusive. We examined alterations in effective connectivity induced by rTMS using concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) in children with ASD. TMS-EEG data were acquired from 12 children diagnosed with ASD both before and following rTMS treatment. The rTMS intervention regimen included delivering 5-s trains at a frequency of 15 Hz, with 10-min intervals between trains, targeting the left parietal lobe. This was conducted on each consecutive weekday over 3 weeks, totaling 15 sessions. The dynamic EEG network analysis revealed that following the rTMS intervention, long-range feedback connections within the brains of ASD patients were strengthened (e.g., frontal to parietal regions, frontal to occipital regions, and frontal to posterior temporal regions), and short-range connections were weakened (e.g., between the bilateral occipital regions, and between the occipital and posterior temporal regions). In alignment with alterations in network connectivity, there was a corresponding amelioration in fundamental ASD symptoms, as assessed through clinical scales post-treatment. According to our findings, people with ASD may have increased long-range frontal-posterior feedback connection on application of rTMS to the parietal lobe.

Background Anorexia nervosa (AN) has been characterised as a psychiatric disorder associated with increased control. Currently, it remains difficult to predict treatment response in patients with AN. Their cognitive abilities are known to be resistant to treatment. It has been established that the frontoparietal control network (FPCN) is the direct counterpart of the executive control network. Therefore, the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in AN.Aims The study aimed to investigate the association between resting-state functional connectivity (RSFC) of the FPCN, clinical symptoms and treatment response in patients with AN.Methods In this case-control study, 79 female patients with AN and no prior treatment from the Shanghai Mental Health Center and 40 matched healthy controls (HCs) were recruited from January 2015 to March 2022. All participants completed the Questionnaire Version of the Eating Disorder Examination (version 6.0) to assess the severity of their eating disorder symptoms. Additionally, RSFC data were obtained from all participants at baseline by functional magnetic resonance imaging. Patients with AN underwent routine outpatient treatment at the 4th and 12th week, during which time their clinical symptoms were evaluated using the same measures as at baseline.Results Among the 79 patients, 40 completed the 4-week follow-up and 35 completed the 12-week follow-up. The RSFC from the right posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (dlPFC) increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety symptoms. By multiple linear regression, the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image, after controlling for age, age of onset and body mass index. The RSFC in the dlPFC to the middle temporal gyrus and the superior frontal gyrus may be significant factors in the treatment response to binge eating and loss of control/overeating in patients with AN.Conclusions Alterations in RSFC in the FPCN appear to affect self-reported eating disorder symptoms and treatment response in patients with AN. Our findings offer new insight into the pathogenesis of AN and could promote early prevention and treatment.

IntroductionGestational diabetes mellitus (GDM) is a form of gestational diabetes mellitus characterized by insulin resistance and abnormal function of pancreatic beta cells. In recent years, genomic association studies have revealed risk and susceptibility genes associated with genetic susceptibility to GDM. However, genetic predisposition cannot explain the rising global incidence of GDM, which may be related to the increased influence of environmental factors, especially the gut microbiome. Studies have shown that gut microbiota is closely related to the occurrence and development of GDM. This paper reviews the relationship between gut microbiota and the pathological mechanism of GDM, in order to better understand the role of gut microbiota in GDM, and to provide a theoretical basis for clinical application of gut microbiota in the treatment of related diseases.MethodsThe current research results on the interaction between GDM and gut microbiota were collected and analyzed through literature review. Keywords such as "GDM", "gut microbiota" and "insulin resistance" were used for literature search, and the methodology, findings and potential impact on the pathophysiology of GDM were systematically evaluated.ResultsIt was found that the composition and diversity of gut microbiota were significantly associated with the occurrence and development of GDM. Specifically, the abundance of certain gut bacteria is associated with an increased risk of GDM, while other changes in the microbiome may be associated with improved insulin sensitivity. In addition, alterations in the gut microbiota may affect blood glucose control through a variety of mechanisms, including the production of short-chain fatty acids, activation of inflammatory pathways, and metabolism of the B vitamin group.DiscussionThe results of this paper highlight the importance of gut microbiota in the pathogenesis of GDM. The regulation of the gut microbiota may provide new directions for the treatment of GDM, including improving insulin sensitivity and blood sugar control through the use of probiotics and prebiotics. However, more research is needed to confirm the generality and exact mechanisms of these findings and to explore potential clinical applications of the gut microbiota in the management of gestational diabetes. In addition, future studies should consider the interaction between environmental and genetic factors and how together they affect the risk of GDM.

External verification based on ground-based data is commonly used to assess the accuracy of satellite products for total ozone. However, the spatial representativeness of ground-based observations at the pixel scale and the effects of the spatial mismatch between ground observations and satellite pixels are often overlooked. Therefore, this study focused on an Ozone Monitoring Instrument (OMI) and proposed a novel method to evaluate spatial representativeness using the total ozone product itself without relying on higher spatial resolution imagery from other sensors. A Pixel-level Spatial Mismatch Index (PSMI) was developed to quantify the peaks and stable intervals of the spatial response to the relative deviation of total ozone observations. The analysis revealed that increased uncertainty at the pixel edges can cause significant relative deviation, with the peak deviation occurring within a range of 4–7 km near the pixel boundary. The position of the high precision interval in PSMI was found to be 10 km, with mean values of 3.70 % and standard deviations of 3.45 % for the relative deviation. This interval is spatially distance-independent and can be observed on both sides of the pixel boundary. These findings highlight the importance of considering spatial patterns between satellite pixels and ground stations for external validation. Furthermore, avoiding a spatial response peak of the relative deviation at the pixel edge is crucial. Overall, this research provides new perspectives and insights for the verification of total ozone products. By considering these factors mentioned above, future verification of total ozone products can be improved, leading to enhanced their evaluation systems.

Background and objectiveAberrant epigenetic regulation and increased oxidative stress in the placenta play a significant role in placental pathophysiology and fetal programming in preeclampsia, a hypertensive disorder in human pregnancy. The purpose of the study is to investigate if hypermethylation of histone H3K9 occurs in placental trophoblasts from preeclampsia.MethodsTrophoblasts were isolated and cultured from 14 placentas, 7 from normotensive pregnant women and 7 from preeclamptic pregnancies. Methylated H3K9 expression and antioxidant superoxide dismutase expression were determined by Western blot. We also examined consequences of oxidative stress and the downstream effects of histone methyltransferase inhibition on H3K9 expression associated with antioxidant CuZn-SOD and Mn-SOD expression in placental trophoblasts.ResultsWe found that expression of mono-, di-, and tri-methylation of histone H3 lysine 9 (H3K9me1, H3K9me2 and H3K9me3) was significantly increased, p

Abstract High heritability and strong correlation have been observed in breast and ovarian cancers. However, their shared genetic architecture remained unclear. Linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics (ρ-HESS) were applied to estimate heritability and genetic correlations. Bivariate causal mixture model (MiXeR) was used to qualify the polygenic overlap. Then, stratified-LDSC (S-LDSC) was used to identify tissue and cell type specificity. Meanwhile, the adaptive association test called MTaSPUsSet was performed to identify potential pleiotropic genes. The Single Nucleotide Polymorphisms (SNP) heritability was 13% for breast cancer and 5% for ovarian cancer. There was a significant genetic correlation between breast and ovarian cancers (rg=0.21). Breast and ovarian cancers exhibited polygenic overlap, sharing 0.4 K out 2.8 K of causal variants. Tissue and cell type specificity displayed significant enrichment in female breast mammary, uterus, kidney tissues, and adipose cell. Moreover, the 74 potential pleiotropic genes were identified between breast and ovarian cancers, which were related to the regulation of cell cycle and cell death. We quantified the shared genetic architecture between breast and ovarian cancers and shed light on the biological basis of the co-morbidity. Ultimately, these findings facilitated the understanding of disease etiology.

The inverse model based multi-objective evolutionary algorithm (IM-MOEA) generates offspring by establishing probabilistic models and sampling by the model, which is a new computing schema to replace crossover in MOEAs. In this paper, an active learning Gaussian modeling based multi-objective evolutionary algorithm using population guided weight vector evolution strategy (ALGM-MOEA) is proposed. To properly cope with multi-objective problems with different shapes of Pareto front (PF), a novel population guided weight vector evolution strategy is proposed to dynamically adjust search directions according to the distribution of generated PF. Moreover, in order to enhance the search efficiency and prediction accuracy, an active learning based training sample selection method is designed to build Gaussian process based inverse models, which chooses individuals with the maximum amount of information to effectively enhance the prediction accuracy of the inverse model. The experimental results demonstrate the competitiveness of the proposed ALGM-MOEA on benchmark problems with various shapes of Pareto front.

Deciphering the genetic mechanisms underlying key agronomic and quality traits in potato (Solanum tuberosum L.) is essential for advancing varietal improvement. Phenotypic instability in early clonal generations and inbreeding depression, coupled with the complexity of tetrasomic inheritance, pose significant challenges in constructing mapping populations for the genetic dissection of complex traits. Genome-wide association studies (GWASs) offer an efficient method to establish trait–genome associations by analyzing genetic recombination and mutation events in natural populations. This review systematically examines the application of GWASs in identifying agronomic traits in potato, such as plant architecture, yield components, tuber shape, and resistance to early and late blight and nematodes, as well as quality traits including dry matter, starch, and glycoalkaloid content. Some key chromosomal hotspots identified through GWASs include chromosome 5 associated with tuber yield, starch content, and late blight resistance; chromosome 4 and 10 associations with tuber shape and starch content; chromosomes 1, 9, and 11 associated with plant height, tuber number, glycoalkaloid content, and pest resistance. It elucidates the advantages and limitations of GWASs for genetic loci identification in this autotetraploid crop, providing theoretical insights and a reference framework for the precise localization of key genetic loci and the discovery of underlying genes using GWASs.

Background: An antidiabetic medication regimen is crucial for maintaining glycemic control. Type 2 diabetes mellitus (T2DM) and cognitive dysfunction have a bidirectional relationship. This study aims to explore the impact that adjusting antidiabetic medication regimens has on medication adherence, glycemic control, and cognitive function in patients with T2DM and mild cognitive impairment (MCI). Methods: This is an observational cross-sectional analysis that includes 364 consecutive inpatients with T2DM. Clinical data were collected, medication adherence was assessed using the Medication Adherence Report Scale (MARS-5), and cognitive status was evaluated using the Chinese version of the Montreal Cognitive Assessment (MoCA) and Mini-mental State Examination (MMSE). These data were obtained both during hospitalization and at a three-month follow-up. Multivariable logistic regression analysis was applied to determine the association between changes in medication regimens and medication adherence, glycemic control, and cognitive function. Results: Baseline medication adherence was high across all three different cognitive status groups, with no significant difference in MARS-5 scores. At the 3-month follow-up, the group with a high adjustment ratio of antidiabetic medication regimens showed an increase in their hemoglobin A1c (HbA1c) level compared to the baseline, while the group with a low adjustment ratio showed a decrease in this level. In addition, the MoCA, MMSE, and MARS-5 scores of the high-adjustment group were significantly lower than those of the low-adjustment group. Conclusions: A high ratio of medication adjustment was significantly associated with worse medication adherence and glycemic control in T2DM patients with MCI. Patients with a low ratio of medication adjustment had good adherence and better glycemic control. Clinicians should take cognitive status into account when adjusting antidiabetic regimens for T2DM patients and may need to provide additional guidance to patients with cognitive impairment to improve adherence and glycemic outcomes.

Background: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is an effective treatment for refractory epilepsy; however, seizure outcome varies among individuals. Identifying a reliable noninvasive biomarker to predict good responders would be helpful. Objectives: To test whether the functional connectivity between the ANT-DBS sites and the seizure foci correlates with effective seizure control in refractory epilepsy. Methods: We performed a proof-of-concept pilot study of patients with focal refractory epilepsy receiving ANT-DBS. Using normative human connectome data derived from 1000 healthy participants, we investigated whether intrinsic functional connectivity between the seizure foci and the DBS site was associated with seizure outcome. We repeated this analysis controlling for the extent of seizure foci, distance between the seizure foci and DBS site, and using functional connectivity of the ANT instead of the DBS site to test the contribution of variance in DBS sites. Results: Eighteen patients with two or more seizure foci were included. Greater functional connectivity between the seizure foci and the DBS site correlated with more favorable outcome. The degree of functional connectivity accounted for significant variance in clinical outcomes (DBS site: |r| = 0.773, p

Abstract Background Dietary carotenoids have been proven to improve intestinal disorders like inflammatory bowel disease and colon cancer, yet little is known about the link between dietary carotenoids and constipation. This study aims to examine the relationship between dietary carotenoids intake and constipation, using data from the National Health and Nutrition Examination Survey (NHANES) 2005–2010. Methods A total of 11,722 participants were enrolled. Chronic constipation was defined as type 1 (separate hard lumps, like nuts) and type 2 (sausage-like, but lumpy) in the Bristol stool form scale (BSFS). Carotenoids intake was obtained from the average of two 24-hour dietary recall questionnaires (if only one 24-hour was available, we used it) and divided into quartiles (Q). The prevalence of constipation was calculated across men and women individuals. The relationship between dietary carotenoids intake and constipation in men and women was assessed with weighted logistic regression and smoothed curve fitting after adjusting confounders, with results displayed as weighted odds ratio (OR) with 95% confidence intervals (95% CI). The model was further stratified by age, race, and HEI 2015 scores (with median as cutoff) among men and women. Results The total weighted prevalence of chronic constipation in this study was 8.08%, 11.11% in women and 5.18% in men. After multivariable adjustment, compared with the lowest intake, participants with the highest dietary lycopene intake (ORQ4 vs. Q1= 0.55, 95% CI: 0.36–0.84, p for trend = 0.01) and total lycopene intake (ORQ4 vs. Q1 = 0.52, 95% CI: 0.34–0.80, p for trend = 0.01) were negatively associated with the risk of chronic constipation in men, whereas increased dietary α-carotene intake reduced the risk of chronic constipation in women (ORQ4 vs. Q1 = 0.69, 95% CI: 0.48–0.98, p for trend = 0.04). Smoothing curve fitting further supported these results and provided evidence of dose-response effects. No association was found between other types of carotenoids and chronic constipation in men and women. Conclusions Increasing lycopene intake may improve bowel function in men while increased α-carotene intake may reduce the risk of chronic constipation in women. Further studies are essential to explore the role that the intake of carotenoids plays in chronic constipation.

Abstract Background Several previous studies investigated the associations between temperature and influenza in a single city or region without a national picture. The attributable risk of influenza due to temperature and the corresponding driving factors were unclear. This study aimed to evaluate the spatial distribution characteristics of attributable risk of Influenza-like illness (ILI) caused by adverse temperatures and explore the related driving factors in the United States. Methods ILI, meteorological factors, and PM2.5 of 48 states in the United States were collected during 2011–2019. The time-stratified case-crossover design with a distributed lag non-linear model was carried out to evaluate the association between temperature and ILI at the state level. The multivariate meta-analysis was performed to obtain the combined effects at the national level. The attributable fraction (AF) was calculated to assess the ILI burden ascribed to adverse temperatures. The ordinary least square model (OLS), spatial lag model (SLM), and spatial error model (SEM) were utilized to identify driving factors. Results A total of 7,716,115 ILI cases were included in this study. Overall, the temperature was negatively associated with ILI risk, and lower temperature gave rise to a higher risk of ILI. AF ascribed to adverse temperatures differed across states, from 49.44% (95% eCI: 36.47% ~ 58.68%) in Montana to 6.51% (95% eCI: -6.49% ~ 16.46%) in Wisconsin. At the national level, 29.08% (95% eCI: 27.60% ~ 30.24%) of ILI was attributable to cold. Per 10,000 dollars increase in per-capita income was associated with the increment in AF (OLS: β = -6.110, P = 0.021; SLM: β = -5.496, P = 0.022; SEM: β = -6.150, P = 0.022). Conclusion The cold could enhance the risk of ILI and result in a considerable proportion of ILI disease burden. The ILI burden attributed to cold varied across states and was higher in those states with lower economic status. Targeted prevention programs should be considered to lower the burden of influenza.

ABSTRACT: Objectives: Faropenem has antituberculosis activity in vitro but its utility in treating patients with tuberculosis (TB) is unclear. Methods: We conducted an open-label, randomized trial in China, involving newly diagnosed, drug-susceptible pulmonary TB. The control group was treated with the standard 6-month regimen. The experimental group replaced ethambutol with faropenem for 2 months. The primary outcome was the treatment success rate after 6 months of treatment. Noninferiority was confirmed if the lower limit of a 95% one-sided confidence interval (CI) of the difference was greater than −10%. Results: A total of 227 patients eligible for the study were enrolled in the trial group and the control group in a ratio of 1:1. Baseline characteristics of participants were similar in both groups. In the modified intention-to-treat population, 88.18% of patients in the faropenem group achieved treatment success, and 85.98% of those in the control group were successfully treated, with a difference of 2.2% (95% CI, −6.73-11.13). In the per-protocol population, treatment success was 96.04% in the faropenem group and 95.83% in the control group, with a difference of 2.1% (95% CI, −5.31-5.72). The faropenem group showed noninferiority to the control group in the 6-month treatment success rates. The faropenem group had significantly fewer adverse events (P

BackgroundThe common clinical symptoms and immunopathological mechanisms have been observed among multiple autoimmune diseases (ADs), but the shared genetic etiology remains unclear.MethodsGWAS summary statistics of seven ADs were downloaded from Open Targets Genetics and Dryad. Linkage disequilibrium score regression (LDSC) was applied to estimate overall genetic correlations, bivariate causal mixture model (MiXeR) was used to qualify the polygenic overlap, and stratified-LDSC partitioned heritability to reveal tissue and cell type specific enrichments. Ultimately, we conducted a novel adaptive association test called MTaSPUsSet for identifying pleiotropic genes.ResultsThe high heritability of seven ADs ranged from 0.1228 to 0.5972, and strong genetic correlations among certain phenotypes varied between 0.185 and 0.721. There was substantial polygenic overlap, with the number of shared SNPs approximately 0.03K to 0.21K. The specificity of SNP heritability was enriched in the immune/hematopoietic related tissue and cells. Furthermore, we identified 32 pleiotropic genes associated with seven ADs, 23 genes were considered as novel genes. These genes were involved in several cell regulation pathways and immunologic signatures.ConclusionWe comprehensively explored the shared genetic architecture across seven ADs. The findings progress the exploration of common molecular mechanisms and biological processes involved, and facilitate understanding of disease etiology.

Background: Observational studies have previously demonstrated a significant relationship among both metabolic syndrome (Mets) and colorectal cancer (CRC). Whether there is a causal link remains controversial. Objective: To clarify whether Mets and their components have a causal effect on colorectal cancer, we have carried out a bidirectional Mendelian randomization analysis (MR). Methods: This study started from genome-wide association data for Mets and its 5 components (hypertension, waist circumference, fasting blood glucose, serum triglycerides, and serum high-density lipoprotein cholesterol) and colorectal cancer. Mendelian randomization (MR) techniques were used in the study to examine their associations. Results: After Benjamini-Hochberg multiple corrections, genetically predicted significant causal link exists between WC (waist circumference) and CRC. The OR was 1.35 (95 % CI: 1.08–1.69; p = 0.0096). Other Mets components (HBP, FBG, TG, HDL), on the other hand, found no evidence of a genetic link between CRC and Mets. In addition, MR results showed that CRC was not causally related to either Mets or the components. We get the same result in the validated dataset. Conclusion: According to the bidirectional MR investigation shows a significant causal relationship among obesity and CRC in the Mets component but no causal relationship in the opposite direction.

Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and its pathophysiological mechanisms remain unknown. IRSp53 family members, such as BAIAP2L1, participate in the progression of multiple tumors. However, the role of BAIAP2L2 in HCC remains unclear. This study comprehensively analyzed the potential role of BAIAP2L2 in HCC using bioinformatic techniques. The expression of BAIAP2L2 in HCC was analyzed using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), and Human Protein Atlas (HPA) databases and in vitro experiments. In addition, the prognostic value of BAIAP2L2 in HCC was analyzed using the TCGA database. TCGA and GEO database were used to analyze the role of BAIAP2L2 in immune features. We also explored the function of BAIAP2L2 in methylation and cuprotosis. The CellMiner database was used to analyze the relationship between BAIAP2L2 expression and drug sensitivity. Our study revealed that BAIAP2L2 is overexpressed in HCC and promotes the migration and invasion of HCC cells. BAIAP2L2 may affect the prognosis of HCC by regulating immunity, methylation, and cuprotosis. BAIAP2L2 is a novel HCC prognostic gene involved in immune infiltration associated with cuprotosis and may be a potential prognosis and therapeutic target for HCC.

Osteosarcoma(OS) is a common primary malignant bone tumor, which mostly occurs in children and adolescents. Currently, chemotherapy drugs for the clinical treatment of OS have high side effects and patients are prone to chemotherapy resistance, which reduces the therapeutic effect. Therefore, the development of new therapeutic drugs is very important to reduce the toxicity and adverse reactions of drugs and improve the survival rate of patients. At present, the antitumor activity of traditional Chinese medicine monomers has received extensive attention because of its safety and efficacy. Asiatic acid (AA) is a naturally pentacyclic triterpenoids extracted from Centella asiatica. The aim of this study was to evaluate the effect and mechanism of AA on OS cells in vitro and in vivo. In vitro results showed that AA inhibited the proliferation, migration and invasion of OS cells and was able to induce apoptosis and cycle arrest. In vivo results showed that AA inhibited the growth of OS and the size of lung metastasis in nude mice. Network pharmacology, molecular docking and in vitro experiments prove that AA may play a role in the treatment of OS by inhibiting PI3K/AKT and NF-κB signaling pathways. Our study shows that AA can act on multiple targets of OS and regulate multiple pathways to intervene in the occurrence and development of OS, which may provide reference for the clinical application and development of AA.

Gastrointestinal cancer is a common malignancy with high mortality and poor prognosis. Therefore, developing novel effective markers and therapeutic targets for gastrointestinal cancer is currently a challenging and popular topic in oncology research. Accumulating studies have reported that N6-methyladenosine is the most abundant epigenetic modification in eukaryotes. N6-methyladenosine plays an essential role in regulating RNA expression and metabolism, including splicing, translation, stability, decay, and transport. FTO, the earliest demethylase discovered to maintain the balance of N6-adenosine methylation, is abnormally expressed in many tumors. In this review, we discuss the molecular structure and substrate selectivity of FTO. we focus on the role of FTO in gastrointestinal tumor proliferation, migration, invasion, apoptosis, autophagy, immune microenvironment, and its molecular mechanisms. We also discuss its potential in the treatment of gastrointestinal cancers.

PurposeThe lymphocyte/C-reactive protein (LCR) is a novel immunoinflammatory score and prognostic marker, but the relationship between lymphocyte/C-reactive proteins and clinical outcomes in patients with upper gastrointestinal cancers remains controversial. This study aimed to evaluate the relationship between LCR and the prognosis of upper gastrointestinal cancer by systematic evaluation and meta-analysis.MethodsWe systematically searched PubMed, EMBASE, Cochrane, and Web of Science databases to obtain related studies on the relationship between LCR and esophageal cancer (EC), gastric cancer (GC), and esophagogastric junction cancers (EGJ), and used hazard ratio (HR), 95% confidence interval (95%CI) to evaluate the prognostic value of LCR. Outcome measures included overall survival (OS) and disease-free survival (DFS).ResultsEight retrospective cohort studies with 2838 patients were included. Meta-analysis showed that patients with low LCR cancers had poor overall survival OS and disease-free survival DFS (HR=2.18, 95%CI=1.87-2.55; HR=1.88, 95%CI=1.56-2.26). Subgroup analysis based on cancer type, treatment modality, gender, T stage, TNM stage, country, and LCR threshold showed that lower LCR levels were all associated with worse OS and DFS (P

Thermoelectric technology directly enables both power generation and electronic cooling. Here, the authors realize high-performance SnSe crystals with promising device efficiencies by modulating crystal and band structures.

Abstract Aberrant expression of circRNAs is closely associated with the progression of gastric cancer; however, the specific mechanisms involved remain unclear. Our aim was to identify new gastric cancer biomarkers and explore the molecular mechanisms of gastric cancer progression. Therefore, we analyzed miRNA and circRNA microarrays of paired early-stage gastric cancer samples. Our study identified a new circRNA called hsa_circ_0069382, that had not been reported before and was expressed at low levels in gastric cancer tissues. Our study also included bioinformatics analyses which determined that the high expression of hsa_circ_0069382 regulated the BTG anti-proliferation factor 2 (BTG2)/ focal adhesion kinase (FAK) axis in gastric cancer lines by sponging for miR-15a-5p. Therefore, proliferation, invasion, and migration of gastric cancer is impacted. miR-15a-5p overexpression partially restored the effects of hsa_circ_0069382. This study provides potential new therapeutic options and a future direction to explore for gastric cancer treatment, and biomarkers. Graphical Abstract

Soybean (Glycine max (L.) Merr.) is a globally significant crop, widely cultivated for oilseed production and animal feeds. In recent years, the rapid growth of multi-omics data from thousands of soybean accessions has provided unprecedented opportunities for researchers to explore genomes, genetic variations, and gene functions. To facilitate the utilization of these abundant data for soybean breeding and genetic improvement, the SoybeanGDB database (https://venyao.xyz/SoybeanGDB/) was developed as a comprehensive platform. SoybeanGDB integrates high-quality de novo assemblies of 39 soybean genomes and genomic variations among thousands of soybean accessions. Genomic information and variations in user-specified genomic regions can be searched and downloaded from SoybeanGDB, in a user-friendly manner. To facilitate research on genetic resources and elucidate the biological significance of genes, SoybeanGDB also incorporates a variety of bioinformatics analysis modules with graphical interfaces, such as linkage disequilibrium analysis, nucleotide diversity analysis, allele frequency analysis, gene expression analysis, primer design, gene set enrichment analysis, etc. In summary, SoybeanGDB is an essential and valuable resource that provides an open and free platform to accelerate global soybean research.

Abstract Mood disorders are associated with elevated inflammation, and the reduction of symptoms after multiple treatments is often accompanied by pro-inflammation restoration. A variety of neuromodulation techniques that regulate regional brain activities have been used to treat refractory mood disorders. However, their efficacy varies from person to person and lack reliable indicator. This review summarizes clinical and animal studies on inflammation in neural circuits related to anxiety and depression and the evidence that neuromodulation therapies regulate neuroinflammation in the treatment of neurological diseases. Neuromodulation therapies, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES), electroconvulsive therapy (ECT), photobiomodulation (PBM), transcranial ultrasound stimulation (TUS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS), all have been reported to attenuate neuroinflammation and reduce the release of pro-inflammatory factors, which may be one of the reasons for mood improvement. This review provides a better understanding of the effective mechanism of neuromodulation therapies and indicates that inflammatory biomarkers may serve as a reference for the assessment of pathological conditions and treatment options in anxiety and depression.

Background: The periosteum plays a crucial role in the development and injury healing process of bone. The purpose of this study was to construct a biomimetic periosteum with a double cell sheet for bone tissue regeneration. Methods: In vitro, the human amniotic mesenchymal stem cells (hAMSCs) sheet was first fabricated by adding 50 ​μg/ml ascorbic acid to the cell sheet induction medium. Characterization of the hAMSCs sheet was tested by general observation, microscopic observation, live/dead staining, scanning electron microscopy (SEM) and hematoxylin and eosin (HE) staining. Afterwards, the osteogenic cell sheet and vascular cell sheet were constructed and evaluated by general observation, alkaline phosphatase (ALP) staining, Alizarin Red S staining, SEM, live/dead staining and CD31 immunofluorescent staining for characterization. Then, we prepared the double cell sheet. In vivo, rat calvarial defect model was introduced to verify the regeneration of bone defects treated by different methods. Calvarial defects (diameter: 4 ​mm) were created of Sprague–Dawley rats. The rats were randomly divided into 4 groups: the control group, the osteogenic cell sheet group, the vascular cell sheet group and the double cell sheet group. Macroscopic, micro-CT and histological evaluations of the regenerated bone were performed to assess the treatment results at 8 weeks and 12 weeks after surgery. Results: In vitro, hAMSCs sheet was successfully prepared. The hAMSCs sheet consisted of a large number of live hAMSCs and abundant extracellular matrix (ECM) that secreted by hAMSCs, as evidenced by macroscopic/microscopic observation, live/dead staining, SEM and HE staining. Besides, the osteogenic cell sheet and the vascular cell sheet were successfully prepared, which were verified by general observation, ALP staining, Alizarin Red S staining, SEM and CD31 immunofluorescent staining. In vivo, the macroscopic observation and micro-CT results both demonstrated that the double cell sheet group had better effect on bone regeneration than other groups. In addition, histological assessments indicated that large amounts of new bone had formed in the calvarial defects and more mature collagen in the double cell sheet group. Conclusion: The double cell sheet could promote to repair calvarial defects of rats and accelerate bone regeneration. The translational potential of this article: We successfully constructed a biomimetic cell-sheet-engineered periosteum with a double cell sheet by a simple, low-cost and effective method. This biomimetic periosteum may be a promising therapeutic strategy for the treatment of bone defects, which may be used in clinic in the future.