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ObjectiveChanges in serum thyroid hormone levels may affect cognitive functioning in euthyroid individuals. This study used representative data from the National Health and Nutrition Examination Survey (NHANES) to comprehensively examine the association of thyroid hormones with different tests of cognitive functioning among US elderly people aged ≥60 years.MethodsThis study was a cross-sectional preliminary study with a total of 734 participants from the NHANES 2011-2012 survey. Thyroid function was measured using competitive binding immune-enzymatic assays, while cognitive functioning was measured using a series of assessments, including the Consortium to Establish a Registry for Alzheimer’s Disease-Word Learning (CERAD W-L), Animal Fluency Test, and Digit Symbol Substitution Test (DSST). Weighted multiple linear regression models and binary logistic regression analyses were used to examine the association between thyroid hormone levels and cognitive functioning. All statistical analyses were performed using SPSS version 20.0, and R software.ResultsWeighted multivariable linear regression showed that FT3 was negatively associated with the Animal Fluency Test and DSST (β=-0.113, 95% CI: -3.279, -0.803, P=0.001; β=-0.062, 95% CI: -6.565, -0.470, P=0.024, respectively) after adjustment for potential covariates. subgroup analysis stratified by sex revealed a negative association between FT3 levels and the Animal Fluency Test in men (β=-0.163, 95% CI: -4.643, -1.153, P=0.001). For female participants, FT3 was negatively associated with not only the Animal Fluency Test but also DSST (β=-0.099, 95% CI: -3.543, -0.093, P=0.039; β=-0.093, 95% CI: -10.288, -1.326, P=0.011). Binary logistic regression showed that the significantly increased adjusted odds ratios (aORs) (95% CI) between the risk of impaired cognitive functioning and FT3 across Q3 and Q4 compared with Q1 were 2.025 (1.092, 3.753) and 2.365 (1.261, 4.433), respectively, for DSST in overall participants. Furthermore, there were significant differences between participants with and without impaired cognitive functioning for serum FT3 levels in overall participants based on DSST score (P=0.020).ConclusionsThere was a significant inverse relationship between FT3 levels within the normal range and cognitive functioning after adjusting for potential covariates. Future longitudinal cohort studies should be conducted to determine the causal relationship between thyroid hormone levels and cognitive functioning.

Peri-implantitis, a complex condition that can lead to dental implant failure, is characterized by inflammatory destruction resulting from immune dysregulation. Oral microbial dysbiosis and foreign body stimulation are the main factors contributing to such dysregulation, impairing immune cell function and triggering an inflammatory response. Immune dysregulation plays a critical role in the pathophysiology of peri-implantitis, impacting the balance of T cell subsets, the production of inflammatory factors, and immune-related molecular signaling pathways. Understanding the relationship between immune dysregulation and peri-implantitis is crucial for developing targeted strategies for clinical diagnosis and individualized treatment planning. This review explores the similarities and differences in the immune microenvironment of oral bacterial infections and foreign body rejection, analyzes the relevant molecular signaling pathways, and identifies new key targets for developing innovative immunotherapeutic drugs and effective and personalized treatment modalities for peri-implantitis. Additionally, it addresses the challenges and potential directions for translating immunotherapy into clinical practice for peri-implantitis, offering insights that bridge the gaps in current literature and pave the way for future research.

Within-sample variation in cotton fiber length is a major factor influencing the production and quality of yarns. The textile industry has been searching for approaches of improving the long fiber fraction and minimizing the short fiber fraction within a cotton sample to produce superior fiber and yarn quality. USTER® High Volume Instrument (HVI) has been widely used for a rapid assessment of cotton fiber length traits from a fiber bundle. However, its effectiveness for genetic studies has been questioned due to the indirect estimations of the cotton fiber traits that cannot be measured from a fiber bundle. To overcome the limits of the HVI fiber length traits, we utilized the Advanced Fiber Information System (AFIS) measuring fiber length traits directly from individual fibers based on weight or number. Comparative fiber length analyses showed AFIS provided higher sensitivity in detecting the fiber length variations within and among cotton samples than HVI. The weight-based AFIS length traits were strongly correlated with the corresponding HVI lengths, whereas the number-based AFIS mean length showed a relatively weaker correlation with the HVI lengths. Integrations of the weight based-length traits with genome-wide association studies (GWAS) enabled classifying the QTLs specifically associated with long, mean, or short fiber length traits and identified a false positive associated with the indirectly estimated HVI short fiber trait. Unlike the weight based-AFIS length traits, the number-based AFIS length trait did not show a negative correlation with a weight related-HVI property, and identified a single QTL that was not detected by the corresponding HVI trait. These results suggested that integrating the AFIS method with GWAS helped discoveries of the genome loci involved in the within-sample variation in cotton fiber length and characterizations of the fiber length QTLs.

BackgroundCockayne syndrome (CS) is a rare, multisystem, autosomal recessive disorder characterized by cachectic dwarfism, nervous system abnormalities, and premature aging. Mutations in the ERCC6 and ERCC8 genes are the predominant causes of Cockayne syndrome, with ERCC6 gene mutations present in approximately 75% of cases.MethodsTrio-based whole-exome sequencing (trio-WES) was employed to identify potential pathogenic variants associated with CS. Preimplantation genetic testing for monogenic disorders (PGT-M) was conducted to prevent the transmission of the pathogenic variant.ResultsTwo compound heterozygous mutations were identified in ERCC6—c.1297G>T (p. Glu433*) and c.1607T>G (p. Leu536Trp)—with c.1297G>T representing a novel mutation. Four blastocysts resulting from intracytoplasmic sperm injection were subjected to biopsy. Genetic analyses revealed that E1 harbored maternal mutations in diploid embryos, E2 and E3 carried both paternal and maternal mutations in non-diploid embryos, and E4 did not carry paternal or maternal mutations in diploid embryos. Following the transfer of the E4 embryos, a single successful pregnancy was achieved.ConclusionThe successful application of PGT-M in this family offers a potential approach for addressing other monogenic diseases. The findings of this study broaden the variant spectrum of ERCC6 and will contribute to the molecular diagnosis and genetic counseling of CS. This case highlights the feasibility and effectiveness of PGT-M in preventing CS and provides valuable insights for similarly affected families.

Diabetic nephropathy (DN) is a common and serious micro-vascular complication of diabetes and a leading cause of end-stage renal disease globally. This disease primarily affects middle-aged and elderly individuals, especially those with a diabetes history of over 10 years and poor long-term blood glucose control. Small ubiquitin-related modifiers (SUMOs) are a group of reversible post-translational modifications of proteins that are widely expressed in eukaryotes. SUMO proteins intervene in the progression of DN by modulating various signaling cascades, such as Nrf2-mediated oxidative stress, NF-κB, TGF-β, and MAPK pathways. Recent advancements indicate that natural products regulating SUMOylation hold promise as targets for intervening in DN. In a previous article published in 2022, we reviewed the mechanisms by which SUMOylation intervenes in renal fibrosis and presented a summary of some natural products with therapeutic potential. Therefore, this paper will focus on DN. The aim of this review is to elucidate the mechanism of action of SUMOylation in DN and related natural products with therapeutic potential, thereby summarising the targets and candidate natural products for the treatment of DN through the modulation of SUMOylation, such as ginkgolic acid, ginkgolide B, resveratrol, astragaloside IV, etc., and highlighting that natural product-mediated modulation of SUMOylation is a potential therapeutic strategy for the treatment of DN as a potential therapeutic strategy.

Arachnoid cysts (ACs) are frequently encountered as incidental findings in the brain, with most cases being asymptomatic and not requiring intervention. However, severe brain malformations caused by ACs are rare. In this study, we describe the case of an 8-day-old female infant with a left mandibular mass that was diagnosed as an insular operculum, which has become disconnected and herniated into the parapharyngeal space through an incompletely ossified greater wing of the sphenoid, caused by a fetal Galassi Type III AC. The newborn also exhibited left hearing impairment, which did not improve at the 6-month follow-up after the cyst peritoneal shunt. This report highlights that ACs that manifest during the early fetal period may protrude from the cranial cavity through an unossified skull, potentially affecting the development of brain tissues.

BackgroundChimeric antigen receptor T-cell (CAR-T) therapy has offered new opportunities for patients with relapsed/refractory B-cell lymphoblastic leukemia (r/r B-ALL). However, cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are the two most common toxicities following CAR-T cell therapy. At present, whether the occurrence of CRS and ICANS will impact CAR-T activity remains unknown; this affects the therapeutic efficacy of CAR-T.MethodsIn this multicenter retrospective study, we enrolled 93 patients with r/r B-ALL receiving anti-CD19 CAR-T cell therapy at four medical centers. We evaluated their complete response (CR) rates, minimal residual disease (MRD)-negative CR rates, and survival outcomes.ResultsAmong the included patients, 76 (81.7%) developed CRS and 16 (5.3%) developed ICANS. Fifteen patients experienced concurrent CRS and ICANS. However, no significant differences were noted in CR or MRD-negative CR rates between patients with and without CRS/ICANS. Furthermore, no significant difference was noted in leukemia-free survival (LFS) (p = 0.869 for CRS and p = 0.276 for ICANS) or overall survival (OS) (p = 0.677 for CRS and p = 0.326 for ICANS) between patients with and without CRS/ICANS. Similarly, patients with concurrent CRS and ICANS exhibited no differences in OS and LFS when compared with other patients. Multivariate analysis showed that the development of CRS and ICANS was not associated with any difference in OS and LFS.ConclusionPatients with CRS/ICANS experience similar clinical outcomes compared with those without CRS/ICANS following anti-CD19 CAR-T therapy.

IntroductionMicroRNAs (miRNAs) have been recognized as promising diagnostic biomarkers for Diabetic Retinopathy (DR) due to their notable upregulation in individuals with the condition. However, the development of highly sensitive miRNAs assays for the rapid diagnosis of DR in clinical settings remains a challenging task.MethodsIn this study, we introduce an enhanced CRISPR/Cas12a assay, leveraging suboptimal PAM (sPAM)-mediated Cas12a trans-cleavage in conjunction with rolling circle amplification (RCA). sPAM was found to perform better than canonical PAM (cPAM) in the detection of Cas12a-mediated ssDNA detection at low concentrations and was used instead of canonical PAM (cPAM) to mediate the detection. The parameters of reactions have also been optimized.Results and discussionIn comparison with cPAM, sPAM has higher sensitivity in the detection of ssDNA at concentrations lower than 10 pM by Cas12a. By replacing cPAM with sPAM in the padlock template of RCA, ultra-high sensitivity for miR-183 detection is achieved, with a detection limit of 0.40 aM. within 25 min and a linear range spanning from 1 aM. to 1 pM. Our assay also exhibits exceptional specificity in detecting miR-183 from other miRNAs. Furthermore, the applicability of our assay for the sensitive detection of miR-183 in clinical serum samples is also validated. This study introduces a groundbreaking assay with excellent performance through a simple modification, which not only addresses existing diagnostic challenges, but also opens exciting new avenues for clinical diagnosis in the realm of DR.

Rice is one of the most important food crops in the world and is important for global food security. However, damage caused by striped stem borer (SSB) seriously threatens rice production and can cause significant yield losses. The development and use of resistant rice varieties or genes is currently the most effective strategy for controlling SSB. We genotyped 201 rice samples using 2849855 high-confidence single nucleotide polymorphisms (SNPs). We conducted a genome-wide association study (GWAS) based on observed variation data of 201 rice cultivars resistant to SSB. We obtained a quantitative trait locus (QTL)-qRSSB4 that confers resistance to SSB. Through annotation and analysis of genes within the qRSSB4 locus, as well as qRT-PCR detection in resistant rice cultivars, we ultimately selected the candidate gene LOC_Os04g34140 (named OsRSSB4) for further analysis. Next, we overexpressed the candidate gene OsRSSB4 in Nipponbare through transgenic methods, resulting in OsRSSB4 overexpressing lines (OsRSSB4OE). In addition, we evaluated the insect resistance of OsRSSB4OE lines using wild type (Nipponbare) as a control. The bioassay experiment results of live plants showed that after 20 days of inoculation with SSB, the withering heart rate of OsRSSB4OE-34 and OsRSSB4OE-39 lines was only 8.3% and 0%, with resistance levels of 1 and 0, respectively; however, the withering heart rate of the wild-type reached 100%, with a resistance level of 9. The results of the in vitro stem bioassay showed that, compared with the wild-type, the average corrected mortality rate of the SSB fed on the OsRSSB4OE line reached 94.3%, and the resistance reached a high level. In summary, we preliminarily confirmed that OsRSSB4 positively regulates the defense of rice against SSB. This research findings reveal new SSB resistance gene resources, providing an important genetic basis for SSB resistance breeding in rice crops.

BackgroundGlobally, early-life adversity (ELA) is linked to an increased risk of developing depression in adulthood; however, only a few studies have examined the specific effects of various types of ELA on depression in children and adolescents. This meta-analysis explores the association between the subtypes of ELA and the risk for youth-onset depression.MethodsWe searched three electronic databases for reporting types of ELA, namely, emotional abuse, physical abuse, sexual abuse, emotional neglect, physical neglect, family conflict/violence, divorce, low socioeconomic status, and left-behind experience, associated with depression before the age of 18 years. Our meta-analysis utilized the odds ratio (OR) and relied on a random effects model. Large heterogeneous effects were detected. Some factors moderated the association between ELA and depression in youths. The homogeneity of variance test and meta-regression analysis were used to detect these relationships.ResultsA total of 87 studies with 213,006 participants were ultimately identified via several strategies in this meta-analysis. Individuals who experienced ELA were more likely to develop depression before the age of 18 years old than those without a history of ELA (OR=2.14; 95% CI [1.93, 2.37]). The results of the subgroup analysis revealed a strong association between ELA and depression in youth, both in terms of specific types and dimensions. Specifically, emotional abuse (OR = 4.25, 95% CI [3.04, 5.94]) was more strongly related to depression in children and adolescents than other forms of ELA were. For both dimensions, threat (OR = 2.60, 95% CI [2.23, 3.02]) was more closely related to depression than deprivation was (OR = 1.76, 95% CI [1.55, 1.99]).ConclusionThis meta-analysis revealed that the adverse effects of a broader consideration of ELA on the risk of youth-onset depression vary according to the subtypes of ELA.Systematic review registationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023405803, identifier 42023405803.

IntroductionCoastal marine ecosystems are among the most ecologically and socio-economically dynamic regions on Earth, and the study of eukaryotic planktonic communities is an important aspect of aquatic ecology. It is essential to monitor plankton biodiversity and identify influencing factors in order to measure human effects on coastal waters and help contribute to ecosystem preservation. Environmental DNA (eDNA) metabarcoding analysis is an advanced toolfor detecting the presence of aquatic organisms, which has revolutionary significance for biodiversity monitoring and real-time detection of wild environments.MethodsIn this study, eDNA metabarcoding was used to study seasonal changes in eukaryotic plankton communities in subtropical coastal waters of the northern South China Sea, to explore how various trophic groups affect the complexity and stability of the species network.ResultsThe results showed that the summer interaction network is looser and had has reduce biodiversitycompared to the spring interaction network. As an important part of the planktonic community, the abundance and diversity of algae reflect the interactions between different species and the influence of environmental factors on the dominant species, particularly temperature and nutrients. In addition, producer diversity set the basis for species network complexity and indirectly affected network stability, while consumer diversity and its flexible predation strategies may directly lead to differences in network stability across seasons. There were close correlations among species interaction, environmental factors and species diversity.DiscussionThis study can help us understand the ecosystem functions throughout the year and the complex interactions of planktonic communities from a multiple trophic level perspective, and provide effective methods for sustainable resource utilization and ecological environmental protection in the future.

BackgroundDisorders of lipid metabolism play a key role in the initiation and progression of chronic kidney disease (CKD). Recently, research on lipid metabolism in CKD has rapidly increased worldwide. However, comprehensive bibliometric analyses in this field are lacking. Therefore, this study aimed to evaluate publications in the field of lipid metabolism in CKD over the past 20 years based on bibliometric analysis methods to understand the important achievements, popular research topics, and emerging thematic trends.MethodsLiterature on lipid metabolism in CKD, published between 2004 and 2023, was retrieved from the Web of Science Core Collection. The VOSviewer (v.1.6.19), CiteSpace (v.6.3 R1), R language (v.4.3.2), and Bibliometrix (v.4.1.4) packages (https://www.bibliometrix.org) were used for the bibliometric analysis and visualization. Annual output, author, country, institution, journal, cited literature, co-cited literature, and keywords were also included. The citation frequency and H-index were used to evaluate quality and influence.ResultsIn total, 1,285 publications in the field of lipid metabolism in CKD were identified in this study. A total of 7,615 authors from 1,885 institutions in 69 countries and regions published articles in 466 journals. Among them, China was the most productive (368 articles), and the United States had the most citations (17,880 times) and the highest H-index (75). Vaziri Nosratola D, Levi Moshe, Fornoni Alessia, Zhao Yingyong, and Merscher Sandra emerged as core authors. Levi Moshe (2,247 times) and Vaziri Nosratola D (1,969 times) were also authors of the top two most cited publications. The International Journal of Molecular Sciences and Kidney International are the most published and cited journals in this field, respectively. Cardiovascular disease (CVD) and diabetic kidney disease (DKD) have attracted significant attention in the field of lipid metabolism. Oxidative stress, inflammation, insulin resistance, autophagy, and cell death are the key research topics in this field.ConclusionThrough bibliometric analysis, the current status and global trends in lipid metabolism in CKD were demonstrated. CVD and DKD are closely associated with the lipid metabolism of patients with CKD. Future studies should focus on effective CKD treatments using lipid-lowering targets.

BackgroundCotton pests have a major impact on cotton quality and yield during cotton production and cultivation. With the rapid development of agricultural intelligence, the accurate classification of cotton pests is a key factor in realizing the precise application of medicines by utilize unmanned aerial vehicles (UAVs), large application devices and other equipment.MethodsIn this study, a cotton insect pest classification model based on improved Swin Transformer is proposed. The model introduces the residual module, skip connection, into Swin Transformer to improve the problem that pest features are easily confused in complex backgrounds leading to poor classification accuracy, and to enhance the recognition of cotton pests. In this study, 2705 leaf images of cotton insect pests (including three insect pests, cotton aphids, cotton mirids and cotton leaf mites) were collected in the field, and after image preprocessing and data augmentation operations, model training was performed.ResultsThe test results proved that the accuracy of the improved model compared to the original model increased from 94.6% to 97.4%, and the prediction time for a single image was 0.00434s. The improved Swin Transformer model was compared with seven kinds of classification models (VGG11, VGG11-bn, Resnet18, MobilenetV2, VIT, Swin Transformer small, and Swin Transformer base), and the model accuracy was increased respectively by 0.5%, 4.7%, 2.2%, 2.5%, 6.3%, 7.9%, 8.0%.DiscussionTherefore, this study demonstrates that the improved Swin Transformer model significantly improves the accuracy and efficiency of cotton pest detection compared with other classification models, and can be deployed on edge devices such as utilize unmanned aerial vehicles (UAVs), thus providing an important technological support and theoretical basis for cotton pest control and precision drug application.

BackgroundReactivate the T cell immunity by PD-1/PD-L1 checkpoint blockade is widely used in non-small cell lung cancer (NSCLC) patients, while the post-translational modification of Programmed death ligand-1 (PD-L1) is commonly existed in various cancer cells, thus increases the complexity and difficulty in therapy development. Ginsenoside Rg3 is an active component of traditional Chinese herb Ginseng with multiple pharmacological effects including immune regulation. However, the effect on the glycosylation of PD-L1 is unknown.MethodsNSCLC cell lines were tested for glycosylation of PD-L1, and the potential mechanisms were investigated. Tumor cell-T cell coculture experiment was conducted and the activation of T cells and cytotoxicity were measured by flow cytometry. In vivo xenograft mouse tumor model was used to investigate the effects of Rg3 on PD-L1-mediated immunosuppression and tumor growth.ResultsHere, we identified PD-L1 is widely N-linked glycosylated in NSCLC cell lines, while Rg3 could inhibit the glycosylation of PD-L1 by downregulating the EGFR signaling and further activate GSK3b-mediated degradation, thus resulted in reduced PD-L1 expression. Moreover, the inhibition of PD-L1 glycosylation promoted the activation and cytotoxicity of T cells under coculture condition. In addition, Rg3 could decrease the tumor volume and enhance anti-tumor T cell immunity as evidence by the upregulated expression of Granzyme B and perforin in CD8+T cells, along with elevated serum IL-2, IFN-g and TNF-a level in Rg3-treated mice.ConclusionsThese results suggest that Rg3 inhibits PD-L1 glycosylation and thus enhance anti-tumor immunity, which provide new therapeutic insight into drug discovery.

ObjectivesDepressive symptoms are the most prevalent comorbidity in individuals with obsessive-compulsive disorder (OCD). The objective of this study was to investigate the dynamic characteristics of resting-state neural activities in OCD patients with depressive symptoms.MethodsWe recruited 29 OCD patients with depressive symptoms, 21 OCD patients without depressive symptoms, and 27 healthy controls, and collected data via structural and functional magnetic resonance imaging (fMRI). We analyzed the fMRI results using the dynamic amplitude of low-frequency fluctuation (dALFF) and support vector machine (SVM) techniques.ResultsCompared with OCD patients without depressive symptoms, OCD patients with depressive symptoms exhibited an increased dALFF in the left precuneus and decreased dALFF in the right medial frontal gyrus. The SVM indicated that the integration of aberrant dALFF values in the left precuneus and right medial frontal gyrus led to an overall accuracy of 80%, a sensitivity of 79%, and a specificity of 100% in detecting depressive symptoms among OCD patients.ConclusionTherefore, our study reveals that OCD patients with depressive symptoms display neural activities with unique dynamic characteristics in the resting state. Accordingly, abnormal dALFF values in the left precuneus and right medial frontal gyrus could be used to identify depressive symptoms in OCD patients.

BackgroundGeneralized pustular psoriasis (GPP) is a severe type of psoriasis. The current treatment primarily relies on corticosteroids and immunosuppressants. In recent years, biologics have been increasingly utilized in the treatment of this disease, and have demonstrated good clinical efficacy. However, children and adolescents are primarily treated with immunosuppressants, which have limited clinical application due to the serious side effects they may cause. At the same time, the effectiveness of current treatments is unsatisfactory. Secukinumab has been widely reported to be effective and safe in treating this disease. However, there are still insufficient data on its use in treating GPP in children.ObjectiveTo conduct a systematic review of the existing literature on the use of secukinumab for treating generalized pustular psoriasis in children and adolescents, and to evaluate its clinical effectiveness and safety.MethodsWe conducted a systematic review of all the literature reporting on the treatment of GPP in children and adolescents with secukinumab.ResultsA total of 7 papers (46 patients) were included in this study. After 12 weeks of treatment, all 46 participants were able to achieve a GPPASI score of 90 or higher, with approximately 96% of patients achieving complete clearing of the lesions (GPPASI 100 or JDA0). Adverse events were reported in 8 patients, the rate of adverse reactions was approximately 17%.ConclusionThe treatment of GPP in children and adolescents with secukinumab has a rapid onset of action and a high safety profile. However, the results of the literature may be influenced by publication bias.

ContextFew studies have directly compared the cognitive characteristics of patients with mild autonomous cortisol secretion (MACS) and Cushing’s syndrome (CS). The effect of surgical or conservative treatment on cognitive function in patients with MACS is still unclear.ObjectiveTo compare the differences in cognitive function between patients with MACS and CS and evaluate the effect of surgery or conservative treatment on cognitive function.MethodsWe prospectively recruited 59 patients with nonfunctional adrenal adenoma (NFA), 36 patients with MACS, and 20 patients with adrenal CS who completed the global cognition and cognitive subdomains assessments. Seventeen MACS patients were re-evaluated for cognitive function after a 12-month follow-up period; of these, eleven underwent laparoscopic adrenalectomy and six received conservative treatment.ResultsPatients with MACS and CS performed worse in the global cognition and multiple cognitive domains than those with NFA (all P

Regulatory T cells (Tregs), characterized by the expression of Forkhead Box P3 (FOXP3), constitute a distinct subset of T cells crucial for immune regulation. Tregs can exert direct and indirect control over immune homeostasis by releasing inhibitory factors or differentiating into Th-like Treg (Th-Treg), thereby actively contributing to the prevention and treatment of autoimmune diseases. The epigenetic regulation of FOXP3, encompassing DNA methylation, histone modifications, and post-translational modifications, governs the development and optimal suppressive function of Tregs. In addition, Tregs can also possess the ability to maintain homeostasis in diverse microenvironments through non-suppressive mechanisms. In this review, we primarily focus on elucidating the epigenetic regulation of Tregs as well as their multifaceted roles within diverse physiological contexts while looking forward to potential strategies involving augmentation or suppression of Tregs activity for disease management, particularly in light of the ongoing global COVID-19 pandemic.

The quality traceability of agricultural products is an important and challenging is issue due to it involves multiple activities carried out by farmers and other stakeholders who must manage multiple heterogeneous data sources collected and generated through a variety of applications, services and devices. An agricultural product information integration and quality traceability model is proposed based on knowledge graph (KG). Through modeling, extraction, fusion, storage, calculation, reasoning and application of knowledge of agricultural products, KG is constructed to integrate the knowledge of agricultural production and monitoring process. In KG, nodes represent agricultural products and their foods, and their related specific things or their property values, lines connect to the agricultural products, food, and their properties, forming network, each node and the relationship has uniqueness, the KG of agricultural products and food is stored in the Neo4j database in graph structure, which is clear and easy to reuse. The 100 batches of carrot pesticide residue test results show that the proposed method is feasible for quality traceability of agricultural products. It provides a technical approach for the quality and safety management of agricultural products “from field to Table”.

BackgroundThis prospective study aimed to investigate the influence of weight difference between implanted prosthesis and removed bone in cementless total hip arthroplasty (THA) on hip awareness and patient-reported outcomes.MethodsA total of 48 patients (56 hips) who underwent primary THA were prospectively enrolled. Implanted prosthesis and removed bone were weighed intraoperatively. Forgotten Joint Score (FJS) and Western Ontario and McMaster Universities (WOMAC) scores were obtained before and at 1 and 3 months after surgery. Patients were divided into groups A, B, and C according to the percentile of the weight difference.ResultsThe mean weight difference of the implanted prosthesis and removed bone was 117.97 ± 47.35 g. A negative correlation was found among the weight differences of the three groups and 1- and 3-month postoperative FJS (correlation coefficients, −0.331 and −0.734, respectively). A positive correlation was found among the weight difference of the three groups and 3-month postoperative WOMAC (correlation coefficient, 0.403). A significant difference in 3-month postoperative FJS and WOMAC scores was found among the three groups. The mean 3-month postoperative FJS (79.00) of group C was significantly lower than that of group A (93.32) (P

ObjectiveThis study aimed to evaluate the role of absent in melanoma 2 (AIM2) inflammasome-mediated pyroptosis in the pathogenesis of acute gouty arthritis (AGA) and asymptomatic hyperuricemia(AHU).MethodsA cohort of 30 AGA patients, 30 AHU individuals, and 30 healthy controls (HC) was assembled. Demographic and biochemical data, along with blood samples, were collected. Serum double-stranded DNA (dsDNA) levels were quantified using a fluorescent assay. Transcriptomic and proteomic analysis of AIM2, Caspase-1, GSDMD, IL-1β, and IL-18 in peripheral blood mononuclear cells was performed using qRT-PCR and Western blot. Enzyme-linked immunosorbent assay (ELISA) was employed to measure serum IL-1β and IL-18. Spearman correlation analysis was utilized to assess relationships between variables.ResultsBoth AGA and AHU groups demonstrated elevated metabolic indicators and serum levels of dsDNA, IL-1β, and IL-18 compared to the HC group. AGA patients exhibited higher inflammatory markers than the AHU group. In the AGA group, there was a significant increase in the mRNA and protein levels of AIM2, Caspase-1, GSDMD, IL-1β, and IL-18 (P0.05). In contrast, Caspase-1 and IL-18 proteins were significantly higher in the AHU group (P

In eukaryotes, histone acetylation and deacetylation play an important role in the regulation of gene expression. Histone acetylation levels are reversibly regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Increasing evidence highlights histone acetylation plays essential roles in the regulation of gene expression in plant response to environmental stress. In this review, we discussed the recent advance of histone acetylation in the regulation of abiotic stress responses including temperature, light, salt and drought stress. This information will contribute to our understanding of how plants adapt to environmental changes. As the mechanisms of epigenetic regulation are conserved in many plants, research in this field has potential applications in improvement of agricultural productivity.

Paris polyphylla var. yunnanensis is one of the famous Chinese herbs, in which two saponins (polyphyllin II and polyphyllin VII) have anticancer effects. The endangerment of Paris polyphylla var. yunnanensis, makes the study of optimizing the extraction of polyphyllin II and polyphyllin VII from the leaves of Paris polyphylla var. yunnanensis more important. The study established and optimized the process of ultrasound-assisted extraction for polyphyllin II and polyphyllin VII using the Box Behnken Design method of response surface methodology. The results showed that the optimum extraction conditions for polyphyllin II and polyphyllin VII are ethanol concentration of 73 and 70%, extraction temperature of 43 and 50°C, and number of extraction 3, respectively. Under the above conditions, the contents of polyphyllin II and polyphyllin VII were measured to be 6.427 and 19.015 mg/g (DW). The results showed that the experimental model fitted well, and the response surface methodology (RSM) was feasible to optimize the extraction process of polyphyllin II and polyphyllin VII from Paris polyphylla var. yunnanensis leaves. This method provides an effective approach for the comprehensive development and utilization of non-medicinal parts of Paris polyphylla var. yunnanensis.

BackgroundSchisanlactone E, also known as XueTongSu (XTS), is an active compound extracted from the traditional Tujia medicine Kadsura heteroclita (“XueTong”). Recent studies highlight its anti-inflammatory and antioxidant properties, yet the mechanisms of XTS’s therapeutic effects on Alzheimer’s disease (AD) are unclear. This study aims to elucidate the therapeutic efficacy and mechanisms of XTS in AD.MethodsTen C57BL/6 mice were assigned to the control group (NC), and twenty APP/PS1 transgenic mice were randomly divided into the model group (M) (10 mice) and the XTS treatment group (Tre) (10 mice). After an acclimatization period of 7 days, intraperitoneal injections were administered over a 60-day treatment period. The NC and M groups received saline, while the Tre group received XTS at 2 mg/kg. Learning and memory abilities were assessed using the Morris Water Maze (MWM) test. Histopathological changes were evaluated using hematoxylin and eosin (HE) and Nissl staining, and immunofluorescence was used to assess pathological products and glial cell activation. Cytokine levels (IL-1β, IL-6, TNF-α) in the hippocampus were quantified by qPCR. 16S rDNA sequencing analyzed gut microbiota metabolic alterations, and metabolomic analysis was performed on cortical samples. The KEGG database was used to analyze the regulatory mechanisms of XTS in AD treatment.ResultsXTS significantly improved learning and spatial memory in APP/PS1 mice and ameliorated histopathological changes, reducing Aβ plaque aggregation and glial cell activation. XTS decreased the expression of inflammatory cytokines IL-1β, IL-6, and TNF-α. It also enhanced gut microbiota diversity, notably increasing Akkermansia species, and modulated levels of metabolites such as isosakuranetin, 5-KETE, 4-methylcatechol, and sphinganine. Pathway analysis indicated that XTS regulated carbohydrate metabolism, neuroactive ligand-receptor interactions, and alanine, aspartate, and glutamate metabolism, mitigating gut microbiota dysbiosis and metabolic disturbances.ConclusionXTS ameliorates cognitive deficits, pathological changes, and inflammatory responses in APP/PS1 mice. It significantly modulates the gut microbiota, particularly increasing Akkermansia abundance, and influences levels of key metabolites in both the gut and brain. These findings suggest that XTS exerts anti-AD effects through the microbial-gut-brain axis (MGBA).

ObjectiveThis study aimed to investigate the impact of radiation therapy and radiation enteritis on intestinal flora, providing insights for treatment and prevention.MethodsFecal samples were collected from 16 patients undergoing pelvic radiotherapy at Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital). Samples were collected before and after radiotherapy (27–30Gy), and analyzed using DNA sequencing and biostatistical methods.ResultsPatients with radiation enteritis showed increased α-diversity and β-diversity of intestinal flora compared to those without radiation enteritis. Differences in flora composition were observed, with higher abundance of secondary pathways such as amino acid metabolism, carbohydrate metabolism, cofactors and vitamins metabolism, and lipid metabolism.ConclusionThe study revealed that patients developing radiation enteritis during pelvic radiation therapy had increased diversity and abundance of intestinal flora compared to those who did not develop radiation enteritis. Additionally, patients without radiation enteritis showed significantly higher diversity and abundance of intestinal flora post-radiation compared to pre-radiation.

ObjectiveThe circulating tumor cells (CTCs) could be captured by the peptide functionalized magnetic nanoparticles (Pep@MNP) detection system in pancreatic ductal adenocarcinoma (PDAC). CTCs and the CXCR4 expression were detected to explore their clinical significance. The CXCR4+ CTCs, this is highly metastatic-prone stem cell-like subsets of CTCs (HM-CTCs), were found to be associated with the early recurrence and metastasis of PDAC.MethodsCTCs were captured by Pep@MNP. CTCs were identified via immunofluorescence with CD45, cytokeratin antibodies, and the CXCR4 positive CTCs were assigned to be HM-CTCs.ResultsThe over-expression of CXCR4 could promote the migration of pancreatic cancer cell in vitro and in vivo. In peripheral blood (PB), CTCs were detected positive in 79.0% of all patients (49/62, 9 (0–71)/2mL), among which 63.3% patients (31/49, 3 (0–23)/2mL) were HM-CTCs positive. In portal vein blood (PVB), CTCs were positive in 77.5% of patients (31/40, 10 (0–40)/2mL), and 67.7% of which (21/31, 4 (0–15)/2mL) were HM-CTCs positive CTCs enumeration could be used as diagnostic biomarker of pancreatic cancer (AUC = 0.862), and the combination of CTCs positive and CA19–9 increase shows improved diagnostic accuracy (AUC = 0.963). in addition, PVB HM-CTCs were more accurate to predict the early recurrence and liver metastasis than PB HM-CTCs (AUC 0.825 vs. 0.787 and 0.827 vs. 0.809, respectively).ConclusionsThe CTCs identified by Pep@MNP detection system could be used as diagnostic and prognostic biomarkers of PDAC patients. We identified and defined the CXCR4 over-expressed CTC subpopulation as highly metastatic-prone CTCs, which was proved to identify patients who were prone to suffering from early recurrence and metastasis.

IntroductionMany probiotics have the ability to produce extracellular polysaccharides (EPS). EPS derived from these probiotics has been confirmed to regulate the host intestinal microecological balance and alleviate the symptoms of diseases caused by gastrointestinal microecological imbalance.ResultsLactic acid bacteria (LAB) strain with good exopolysaccharide (EPS) producing ability, namely, Lacticaseibacillus paracasei ZFM54 (L. paracasei ZFM54) was screened. The fermentation conditions of L. paracasei ZFM54 for EPS production were optimized. The EPS54 was characterized by chemical component and monosaccharide composition determination, UV, FT-IR and NMR spectra analysis. Cango red, SEM, AFM and XRD analysis were conducted to characterize the structure of EPS54. The EPS54 effectively reduced the colonization of Helicobacter pylori to AGS cells and recovered the cell morphology. EPS54 could also effectively alleviate the gastritis in the H. pylori-infected mice by down-regulating the mRNA expression levels of pro-inflammatory cytokines IL-6, IL-8, IL-1β and TNF-α and up-regulating the mRNA expression of inflammatory cytokine IL-10 in gastric cells. EPS54 was also found to be able to positively regulate the structure of gastric microbiota.ConclusionThe EPS 54 from L. paracasei ZFM54 can alleviate gastritis in H. pylori-infected mice by modulating the gastric microbiota.

IntroductionThe effects of continuous cropping and rotation cropping, two important tobacco cultivation practices, on soil microbial communities at different stages remain unclear. Different planting patterns have been shown to influence soil physical and chemical properties, which in turn can affect the composition and diversity of soil microbial communities.MethodsIn order to investigate the impact of different planting methods on soil microbial community structure, we selected two representative planting methods: continuous cropping (tobacco) and rotational cropping (tobacco-maize). These methods were chosen as the focal points of our research to explore the potential effects on soil microbial communities. High-throughput sequencing technology was employed to investigate the structure of soil microbial communities, as well as their relationships with soil environmental factors, by utilizing the 16S rRNA, ITS, and 18S genes. Furthermore, the interaction among microorganisms was explored through the application of the Random Matrix Theory (RMT) molecular ecological network approach.ResultsThere was no significant difference in α diversity, but significant difference in β diversity based on Jaccard distance test. Compared to continuous cropping, crop rotation significantly increased the abundance of beneficial prokaryotes Verrucomicrobia and Rhodanobacter. These findings indicate that crop rotation promotes the enrichment of Verrucomicrobia and Rhodanobacter in the soil microbial community. AP and NH4-N had a greater effect on the community structure of prokaryotes and fungi in tobacco soil, while only AP had a greater effect on the community structure of protist. Molecular ecological network analysis showed that the network robustness and Cohesion of rotation were significantly higher than that of continuous cropping, indicating that the complexity and stability of molecular ecological networks were higher in the rotational, and the microbial communities cooperated more effectively, and the community structure was more stable.DiscussionFrom this point of view, rotational cropping is more conducive to changing the composition of soil microbial community, enhancing the stability of microbial network structure, and enhancing the potential ecological functions in soil.

BackgroundDevelopmental Dysplasia of the Hip (DDH) is a skeletal disorder where late-presenting forms often escape early diagnosis, leading to limb and pain in adults. The genetic basis of DDH is not fully understood despite known genetic predispositions.MethodsWe employed Whole Genome Sequencing (WGS) to explore the genetic factors in late-presenting DDH in two unrelated families, supported by phenotypic analyses and in vitro validation.ResultsIn both cases, a novel de novo heterozygous missense mutation in RAF1 (c.193A>G [p.Lys65Glu]) was identified. This mutation impacted RAF1 protein structure and function, altering downstream signaling in the Ras/ERK pathway, as demonstrated by bioinformatics, molecular dynamics simulations, and in vitro validations.ConclusionThis study contributes to our understanding of the genetic factors involved in DDH by identifying a novel mutation in RAF1. The identification of the RAF1 mutation suggests a possible involvement of the Ras/ERK pathway in the pathogenesis of late-presenting DDH, indicating its potential role in skeletal development.

BackgroundFunctional dyspepsia is a highly prevalent digestive disorder. The limited effectiveness of current pharmaceutical interventions necessitates the exploration of alternative therapeutic options for functional dyspepsia. Xiangsha liujunzi decoction, a well-known traditional Chinese medicine formulation, has been widely employed in the treatment of functional dyspepsia in China. Nevertheless, the effectiveness of Xiangsha liujunzi decoction in the treatment of functional dyspepsia remains uncertain.ObjectiveTo examine the effectiveness and safety of Xiangsha liujunzi decoction for treating functional dyspepsia.MethodsWe retrieved seven databases containing randomized controlled trials on functional dyspepsia published up until 31 July 2023. The quality of these studies was evaluated using the Cochrane Risk of Bias assessment tool. The analysis of data was performed using the software RevMan 5.4. The total clinical effectiveness rate was evaluated as the primary outcome. In addition, gastric emptying rate, symptom score and safety evaluation were evaluated as the secondary outcomes.ResultsThe meta-analysis included 23 studies, involving 2,101 individuals. Xiangsha liujunzi decoction demonstrated a significantly higher clinical effectiveness rate compared to the control group (RR 1.27; 95% CI 1.21, 1.33; p < 0.00001). Moreover, it exhibited superior gastric emptying rate and symptom score improvement compared to the control group. Nevertheless, no remarkable differences were detected in safety between Xiangsha liujunzi decoction and the control group (RR 0.67; 95% CI 0.16, 2.76; p = 0.58).ConclusionThe findings of this study suggest that Xiangsha liujunzi decoction exhibits effectiveness and no significant adverse events observed. However, because of the low quality of the enrolled studies, more high-quality and strict design randomized controlled trials are required in the future.

Pyruvate kinase M2 (PKM2), a rate limiting enzyme in glycolysis, is a cellular regulator that has received extensive attention and regards as a metabolic regulator of cellular metabolism and energy. Kidney is a highly metabolically active organ, and glycolysis is the important energy resource for kidney. The accumulated evidences indicates that the enzymatic activity of PKM2 is disturbed in kidney disease progression and treatment, especially diabetic kidney disease and acute kidney injury. Modulating PKM2 post-translational modification determines its enzymatic activity and nuclear translocation that serves as an important interventional approach to regulate PKM2. Emerging evidences show that PKM2 and its post-translational modification participate in kidney disease progression and treatment through modulating metabolism regulation, podocyte injury, fibroblast activation and proliferation, macrophage polarization, and T cell regulation. Interestingly, PKM2 activators (TEPP-46, DASA-58, mitapivat, and TP-1454) and PKM2 inhibitors (shikonin, alkannin, compound 3k and compound 3h) have exhibited potential therapeutic property in kidney disease, which indicates the pleiotropic effects of PKM2 in kidney. In the future, the deep investigation of PKM2 pleiotropic effects in kidney is urgently needed to determine the therapeutic effect of PKM2 activator/inhibitor to benefit patients. The information in this review highlights that PKM2 functions as a potential biomarker and therapeutic target for kidney diseases.

Researchers have found that there may be a correlation between physical activity, executive function, and depression for college students with depression. However, there is limited information available regarding the relationship and interaction between subclinical depression, physical activity, and executive function among college students with subclinical depression. The purpose of this study is to assess the correlation and interaction between subclinical depression, physical activity, and executive function in female college students with subclinical depression. The ActiGraph GT3X was utilized to measure physical activity time, and the colour-word Stroop task was employed to evaluate the executive function of the participants. The findings revealed that female college students with subclinical depression had a significantly lower time for moderate-intensity physical activity compared to healthy female college students. Additionally, the subclinical depression group took significantly longer to complete the colour-word Stroop task compared to the healthy group of female college students. The results of correlation and mediation analyses suggest a negative correlation between BDI-II scores and physical activity time and executive function in female college students with subclinical depression. Moreover, executive function appears to play a partial mediating role in the relationship between physical activity and subclinical depression.

Pandemics caused by respiratory viruses, such as the SARS-CoV-1/2, influenza virus, and respiratory syncytial virus, have resulted in serious consequences to humans and a large number of deaths. The detection of such respiratory viruses in the early stages of infection can help control diseases by preventing the spread of viruses. However, the diversity of respiratory virus species and subtypes, their rapid antigenic mutations, and the limited viral release during the early stages of infection pose challenges to their detection. This work reports a multiplexed microfluidic immunoassay chip for simultaneous detection of eight respiratory viruses with noticeable infection population, namely, influenza A virus, influenza B virus, respiratory syncytial virus, SARS-CoV-2, human bocavirus, human metapneumovirus, adenovirus, and human parainfluenza viruses. The nanomaterial of the nanozyme (Au@Pt nanoparticles) was optimized to improve labeling efficiency and enhance the detection sensitivity significantly. Nanozyme-binding antibodies were used to detect viral proteins with a limit of detection of 0.1 pg/mL with the naked eye and a microplate reader within 40 min. Furthermore, specific antibodies were screened against the conserved proteins of each virus in the immunoassay, and the clinical sample detection showed high specificity without cross reactivity among the eight pathogens. In addition, the microfluidic chip immunoassay showed high accuracy, as compared with the RT-PCR assay for clinical sample detection, with 97.2%/94.3% positive/negative coincidence rates. This proposed approach thus provides a convenient, rapid, and sensitive method for simultaneous detection of eight respiratory viruses, which is meaningful for the early diagnosis of viral infections. Significantly, it can be widely used to detect pathogens and biomarkers by replacing only the antigen-specific antibodies.

BackgroundMembers of the ACR gene family are commonly involved in various physiological processes, including amino acid metabolism and stress responses. In recent decades, significant progress has been made in the study of ACR genes in plants. However, little is known about their characteristics and function in maize.MethodsIn this study, ACR genes were identified from the maize genome, and their molecular characteristics, gene structure, gene evolution, gene collinearity analysis, cis-acting elements were analyzed. qRT-PCR technology was used to verify the expression patterns of the ZmACR gene family in different tissues under salt stress. In addition, Ectopic expression technique of ZmACR5 in Arabidopsis thaliana was utilized to identify its role in response to salt stress.ResultsA total of 28 ZmACR genes were identified, and their molecular characteristics were extensively described. Two gene pairs arising from segmented replication events were detected in maize, and 18 collinear gene pairs were detected between maize and 3 other species. Through phylogenetic analysis, three subgroups were revealed, demonstrating distinct divergence between monocotyledonous and dicotyledonous plants. Analysis of ZmACR cis-acting elements revealed the optional involvement of ZmACR genes in light response, hormone response and stress resistance. Expression analysis of 8 ZmACR genes under salt treatment clearly revealed their role in the response to salt stress. Ectopic overexpression of ZmACR5 in Arabidopsis notably reduced salt tolerance compared to that of the wild type under salt treatment, suggesting that ZmACR5 has a negative role in the response to salt stress.ConclusionTaken together, these findings confirmed the involvement of ZmACR genes in regulating salt stress and contributed significantly to our understanding of the molecular function of ACR genes in maize, facilitating further research in this field.

BackgroundWhether the estimated pulse wave velocity (ePWV) in Chinese patients with hypertension can serve as an independent predictor of cardiovascular and all-cause mortality remains unknown. Therefore, this study investigated the associations between ePWV and cardiovascular and all-cause mortalities and explored potential effect modifiers influencing these relationships. Finally, we compared the ePWV with the brachial-ankle pulse wave velocity (baPWV) to determine which parameter better predicts mortality.MethodsThe population of this longitudinal cohort study was selected from the China H-type Hypertension Registry Study. The exposure and outcome variables were ePWV and all-cause and cardiovascular mortalities, respectively. The Cox proportional hazard regression model was applied to assess the associations between ePWV and all-cause and cardiovascular mortalities. The performances of ePWV and baPWV in predicting death were compared using the receiver operating characteristic (ROC) curve area, net reclassification improvement index (NRI), and integrated discrimination improvement index (IDI).ResultsThis prospective study enrolled 14,232 patients with hypertension. Following an average follow-up of 48 months, 806 individuals succumbed to all-cause mortality, with 397 cases specifically attributed to cardiovascular diseases. The Cox proportional regression analysis revealed a significant association between a 1 m/s increase in ePWV and a 37% higher risk of all-cause mortality (hazard ratio [HR]: 1.37, 95% confidence interval [CI]: 1.31–1.43) as well as a 52% higher risk of cardiovascular mortality (HR: 1.52, 95% CI: 1.43–1.62) in the fully adjusted model. The findings for ePWV according to quartile demonstrated hazard ratios for all-cause mortality for Q2 (10.25

BackgroundImmune checkpoint inhibitors (ICPis) induce autoimmune diseases, including autoimmune polyendocrine syndrome type 2 (APS-2), which is defined as a combination of at least two of the following endocrinopathies: autoimmune thyroid disease, type 1 diabetes, and Addison’s disease. Cases with the full triad are rare. We present a case of an elderly woman who developed APS-2 with the complete triad shortly after starting anti-programmed cell death 1 (anti-PD1) treatment and review the related literature.CaseA 60-year-old woman, without any personal or family history of autoimmune and endocrine diseases, started the immunotherapy of anti-PD1 (camrelizumab) for squamous cell carcinoma of the urethral meatus. She developed primary hypothyroidism with elevated antibodies to thyroid peroxidase and thyroglobulin after 25 weeks of treatment, and developed primary adrenal insufficiency with adrenal crisis and fulminant type 1 diabetes with ketoacidosis after 45 weeks. Therefore, this patient met the diagnosis of APS-2 and was given multiple hormone replacement including glucocorticoid, levothyroxine and insulin therapy. Continuous improvement was achieved through regular monitoring and titration of the dosage.ConclusionsDifferent components of APS-2 may appear at different time points after anti-PD1 administration, and can be acute and life-threatening. A good prognosis can be obtained by appropriate replacement with multiple hormones.InsightsWith the clinical application of ICPis to APS-2, the complexity of its treatment should be paid enough attention.

ObjectiveAccording to the World Alzheimer’s Disease Report in 2015,there were 9.9 million new cases of dementia in the world every year. At present, the number of patients suffering from dementia in China has exceeded 8 million, and it may exceed 26 million by 2040.Mild cognitive impairment (MCI) refers to the pathological state of pre-dementia with the manifestation of the progressive decline of memory or other cognitive functions but without decline of activities of daily life. It is particularly important to prevent or prolong the development of MCI into dementia. Research showing effects of rhythmic auditory stimulation based-movement training(RASMT) interventions on cognitive function is also emerging. Therefore, the present meta-analysis briefly summarize findings regarding the impacts of RASMT programs on cognitive impairment.MethodsData from Pubmed, Embase, and Cochrane Library were utilized. The impact of RASMT on cognitive functions was evaluated using indicators such as overall cognitive status, memory, attention, and executive functions. The REVMAN5.3 software was employed to analyze bias risks integrated into the study and the meta-analysis results for each indicator.ResultsA total of 1,596 studies were retrieved, of which 1,385 non-randomized controlled studies and 48 repetitive studies were excluded. After reviewing titles and abstracts of the remaining 163 articles, 133 irrelevant studies were excluded, 30 studies were downloaded and read the full text. Among 30 articles, 18 articles that did not meet the inclusion criteria were excluded, the other 12 studies were included in this meta-analysis. Utilizing the Cochrane Collaborative Network Bias Risk Assessment Scale, it was found that 11 studies explained the method of random sequence generation, nine studies did not describe allocation concealment, four were single-blinded to all researchers, and eight reported single-blinding in the evaluation of experimental results. In the meta-analysis, the main outcomes showed statistically significant differences in overall cognitive status [MD = 1.19, 95%CI (0.09, 2.29), (p

BackgroundUstekinumab (UST) is approved as an effective therapy for Crohn's disease (CD) in adults. Off-label use is increasing in the pediatric population, more data on safety and efficacy in pediatric patients with CD is urgently needed.AimsThis study aimed to evaluate the clinical efficacy and safety of UST in children and adolescents with Crohn's disease.MethodsThis multicenter retrospective study carried out at three tertiary care centers, and identified children who received their first dose of UST at 18 years old or younger and followed up for a minimum of 24 weeks. Data on demographics, disease behavior, location and activity, treatment history were collected. The primary outcomes were clinical remission at weeks 24–32 and weeks 48–56 of UST therapy. Secondary outcomes were clinical response at the same time points, endoscopic remission, changes in C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin and fecal calprotectin, improvement in growth parameters, and rate of adverse events.ResultsSixteen patients were included, and 11/13 (84.6%) continued to receive UST after 1 year. Our data demonstrate that the clinical remission rates were 41.7% at weeks 24∼32 with the Weighted pediatric CD activity index (wPCDAI) was lower than baseline (43.8, IQR: 31.3–51.9 vs.15, IQR: 5.6–25, p

Virus-induced genomic remodeling and altered gene expression contribute significantly to cancer development. Some oncogenic viruses such as Human papillomavirus (HPV) specifically trigger certain cancers by integrating into the host’s DNA, disrupting gene regulation linked to cell growth and migration. The effect can be through direct integration of viral genomes into the host genome or through indirect modulation of host cell pathways/proteins by viral proteins. Viral proteins also disrupt key cellular processes like apoptosis and DNA repair by interacting with host molecules, affecting signaling pathways. These disruptions lead to mutation accumulation and tumorigenesis. This review focuses on recent studies exploring virus-mediated genomic structure, altered gene expression, and epigenetic modifications in tumorigenesis.

IntroductionAnaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL). Patients with ALK+ LBCLs have poor response and survival outcomes when treated with traditional chemotherapy regiments. The efficacy of second- and third-generation ALK inhibitors has been reported in treating ALK+ LBCLs. Additionally, owing to the plasmablastic morphology and immune features observed in ALK+ LBCLs, plasma cell tumor therapies may be effective for this patient population. In this case report, we utilized a myeloma-like therapy combined with a third-generation ALK inhibitor for a newly diagnosed ALK+ LBCL patient.Case presentationWe reported a 32-year-old male patient diagnosed with ALK+ LBCL. Immunohistochemistry (IHC) analysis revealed a plasma cell immunophenotype characterized by CD138 positivity but negativity for mature B lymphocyte markers. The patient received six cycles of VRD (bortezomib 1.3 mg/m2 d1, 4, 8, and 11; lenalidomide 25 mg qd d1–14; dexamethasone 20 mg d1–2, d4–5, d8–9, and d11–12) and cyclophosphamide (1.0 g q3w) treatment. Lorlatinib (100 mg once daily) was added starting from the second cycle of treatment onwards. After four cycles of treatment, the patient achieved complete remission, which was maintained for more than 6 months after completing chemotherapy, without any significant safety concerns.ConclusionVRD and cyclophosphamide combined with a third-generation ALK inhibitor resulted in durable complete remission for an individual with ALK+ LBCL, suggesting it as a therapeutic option for patients with this subtype.

Studying how populations in various environments differ genetically is crucial for gaining insights into the evolution of biodiversity. In order to pinpoint potential indicators of divergence and adaptation to diverse environments, we conducted a comprehensive analysis of 3,491,868 single nucleotide polymorphisms (SNPs) derived from five populations of Brachymystax lenok. We discovered significant geographic divergence among these 5 populations, which lack evidence of gene flow among them. Our results further demonstrated that the current distribution pattern of Brachymystax lenok are driven by geographical isolation and changes in oceans and rivers. We also performed genome-wide scan and identified the genes evolved to adapt the different environments, including stress response. In general, these results provide genomic support for high-level genetic divergence and the genetic basis of adaptation to different environments.

BackgroundAs a damage-associated molecular pattern protein, high mobility group box 1 (HMGB1) is associated with kidney and systemic inflammation. The predictive and therapeutic value of HMGB1 as a biomarker has been confirmed in various diseases. However, its value in diabetic kidney disease (DKD) remains unclear. Therefore, this study aimed to investigate the correlation between serum and urine HMGB1 levels and DKD progression.MethodsWe recruited 196 patients with type 2 diabetes mellitus (T2DM), including 109 with DKD and 87 T2DM patients without DKD. Additionally, 60 healthy participants without T2DM were also recruited as controls. Serum and urine samples were collected for HMGB1 analysis. Simultaneously, tumor necrosis factor receptor superfamily member 1A (TNFR-1) in serum and kidney injury molecule (KIM-1) in urine samples were evaluated for comparison.ResultsSerum and urine HMGB1 levels were significantly higher in patients with DKD than in patients with T2DM and healthy controls. Additionally, serum HMGB1 levels significantly and positively correlated with serum TNFR-1 (R2 = 0.567, p

ObjectiveWe sought to develop and validate a mortality prediction model for heart transplantation (HT) using nutrition-related indicators, which clinicians could use to identify patients at high risk of death after HT.MethodThe model was developed for and validated in adult participants in China who received HT between 1 January 2015 and 31 December 2020. 428 subjects were enrolled in the study and randomly divided into derivation and validation cohorts at a ratio of 7:3. The likelihood-ratio test based on Akaike information was used to select indicators and develop the prediction model. The performance of models was assessed and validated by area under the curve (AUC), C-index, calibration curves, net reclassification index, and integrated discrimination improvement.ResultThe mean (SD) age was 48.67 (12.33) years and mean (SD) nutritional risk index (NRI) was 100.47 (11.89) in the derivation cohort. Mortality after HT developed in 66 of 299 patients in the derivation cohort and 28 of 129 in the validation cohort. Age, NRI, serum creatine, and triglyceride were included in the full model. The AUC of this model was 0.76 and the C statistics was 0.72 (95% CI, 0.67–0.78) in the derivation cohort and 0.71 (95% CI, 0.62–0.81) in the validation cohort. The multivariable model improved integrated discrimination compared with the reduced model that included age and NRI (6.9%; 95% CI, 1.8%–15.1%) and the model which only included variable NRI (14.7%; 95% CI, 7.4%–26.2%) in the derivation cohort. Compared with the model that only included variable NRI, the full model improved categorical net reclassification index both in the derivation cohort (41.8%; 95% CI, 9.9%–58.8%) and validation cohort (60.7%; 95% CI, 9.0%–100.5%).ConclusionThe proposed model was able to predict mortality after HT and estimate individualized risk of postoperative death. Clinicians could use this model to identify patients at high risk of postoperative death before HT surgery, which would help with targeted preventative therapy to reduce the mortality risk.

Utilizing flowering cherries to enhance suburban landscapes and attract public recreation holds significant economic and social value. However, the current quality of the cherry landscape is compromised due to the absence of variety selection and planning in planting and design. Based on the analysis of public preference, there is significant importance in boosting the sustainability of cherry blossom landscape. However, related research in this domain still needs to be explored. This study examined four representative cherry blossom landscapes in Fujian Province to assess the landscape quality and growth of existing cherry varieties. Subsequently, an improvement model of cherry blossom landscape quality was developed based on image semantic segmentation, aiming to quantify landscape elements. The findings indicated that: (1) There were a total of 46 cherry varieties blooming from January to March in the four representative cherry blossom landscapes. The health grades distribution was as follow: Grade I accounted for 41.3%, Grade II for 39.1%, Grade III for 8.7%, Grade IV for 6.5%, and Grade V for 4.4%. (2) The highest marginal benefit for flake planting was observed when the flowering ratio exceeded 60% or was less than 15%. In contrast, the optimal flowering ratio for the linear cherry blossom landscape for maximum marginal benefit was over 30.0%. (3) The outcomes of the scenic beauty model revealed that the five major factors influencing the scenic beauty were the scene cleanliness (38.04%), plant color composition (25.59%), road (17.79%), plant type (12.88%) and building (2.70%). The results of this study provide valuable objective data references for the planning, design and management of cherry blossom landscapes.

PurposeDepression considerably influences the clinical outcomes, treatment compliance, quality of life, and mortality of hemodialysis patients. Exercise plays a beneficial role in depressive patients, but its quantitative effects remain elusive. This study aimed to summarize the effects of exercise training on depression in patients with end-stage renal disease undergoing hemodialysis.MethodsThe PUBMED, EMBASE, and Cochrane Library databases were systematically searched from inception to April 2023 to identify published articles reporting the effect of exercise training on the depression level of patients with End-Stage Renal Disease undergoing hemodialysis. Data were extracted from the included studies using predefined data fields by two independent researchers. The Cochrane Handbook for Systematic Reviews of Interventions and Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental Studies were employed for quality evaluation.ResultsA total of 22 studies enrolling 1,059 patients who participated in exercise interventions were included. Hemodialysis patients exhibited superior outcomes with intradialytic exercise (SMD = −0.80, 95% CI: −1.10 to −0.49) and lower levels of depression following aerobic exercise (SMD = −0.93, 95%CI: −1.32 to −0.55) compared to combined exercise (c − 0.85, 95% CI: −1.29 to −0.41) and resistance exercise (SMD = −0.40, 95%CI: −0.96 to 0.17). Regarding exercise duration, patients manifested lower depression levels when engaging in exercise activities for a duration exceeding 6 months (SMD = −0.92, 95% CI: −1.67 to −0.17). Concerning the duration of a single exercise session, the most significant improvement was noted when the exercise duration exceeded 60 min (SMD = −1.47, 95% CI: −1.87 to −1.06).ConclusionOur study determined that exercise can alleviate depression symptoms in hemodialysis patients. This study established the varying impacts of different exercise parameters on the reduction of depression levels in hemodialysis patients and is anticipated to lay a theoretical reference for clinicians and nurses to devise tailored exercise strategies for interventions in patients with depression.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database, with registration number CRD42023434181.

Suspended matter in seawater carries abundant nutrients and carbon, playing a significant role in carbon cycle and ecosystem in many oceanic settings such as atolls. The Zhongsha Great Atoll (hereafter ZGA), located in the deep South China Sea, sustains a both regionally and globally important ecosystem. Characteristic of the suspended matter in this area, however, remains poorly investigated. Using a data set encompassing temperature, salinity, depth, and suspended matter concentration (hereafter SMC) of seawater collected respectively in May 2019 (spring-summer monsoon transition period) and June 2020 (summer monsoon outbreak period) in the ZGA, the main components and spatial distribution of suspended matter together with their influencing factors were comprehensively analyzed. Our results show that the components of suspended matter vary widely in space and include more than 20 types of materials such as planktonic remains and biogenic siliceous debris. During the transit between spring and summer monsoons, the SMC in seawater was generally low, with an average value of approximately 3.26 mg L-1, which decreased from the surface to the middle layer and then increased to deep waters; Horizontally, the SMC in the west was generally higher than that in the east likely because the wind-driven current transport significant amounts of particles from the east to the west. During the 2020 summer monsoon outbreak, average SMC in this area was 6.27 mg L-1, higher than that during the 2019 spring-summer monsoon transit. Moreover, significantly higher SMC in the 1-100 m layer and lower SMC in the 150 m layer were observed in the west. Owing to the impact of mesoscale eddies, low SMC in the surface layer and high concentrations in the bottom layer can occur in parts of the ZGA, leading to the deepening of the west-high and east-low distribution layers of SMC during the 2020 summer monsoon outbreak. Notably, we for the first time have observed an anomalously high SMC in the 1–100 m layer of the northwest area during the 2020 summer monsoon outbreak. This anomaly is higher than any previously reported values in the South China Sea and can be attributed to the multiple monsoon impacts. Sources of suspended matter, topography, currents, and wind field were identified as the main factors influencing the spatial distribution of SMC in this area. Our findings provide a basic context for understanding the sources and dynamics of suspended material in atolls.

ObjectiveTo explore the oncological outcomes of sequential laparoscopic gastrectomy after treatment with camrelizumab in combination with nab-paclitaxel plus S-1 for the treatment of gastric cancer with serosal invasion.MethodsThis study is a retrospective cohort study and retrospectively analyzed the clinicopathological data of 128 patients with serosal invasion gastric cancer (cT4NxM0) who received nab-paclitaxel + S-1(SAP) or camrelizumab + nab-paclitaxel + S-1 (C-SAP) regimen and underwent laparoscopy assisted gastrectomy in Fujian Union Hospital from March 2019 to December 2020. The patients were divided into SAP group and C-SAP group. The 2-years overall survival rate, 2-year recurrence free survival rate recurrence rate and initial recurrence time were compared between the two groups.ResultsA total of 128 patients were included, including 90 cases in SAP group and 38 cases in C-SAP group. There were no significant differences in age, gender, gastrectomy method, surgical approach, R0 resection, nerve invasion, vascular invasion, total number of harvested lymph nodes, number of positive lymph nodes and major pathologic response (MPR) rate between the two groups (P>0.05). However, the proportion of ypT0, ypN0 and pCR rate in C-SAP group were significantly higher than those in SAP group (P

Objective: To explore and construct a 3D bone remodeling research model displaying stability, repeatability, and precise simulation of the physiological and biochemical environment in vivo.Methods: In this study, 3D bioprinting was used to construct a bone reconstruction model. Sodium alginate (SA), hydroxyapatite (HA) and gelatin (Gel) were mixed into hydrogel as scaffold material. The osteoblast precursor cells MC3T3-E1 and osteoclast precursor cells RAW264.7 were used as seed cells, which may or may not be separated by polycarbonate membrane. The cytokines osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) were used to induce cell differentiation. The function of scaffolds in the process of bone remodeling was analyzed by detecting the related markers of osteoblasts (alkaline phosphatase, ALP) and osteoclasts (tartrate resistant acid phosphatase, TRAP).Results: The scaffold showed good biocompatibility and low toxicity. The surface morphology aided cell adhesion and growth. The scaffold had optimum degradability, water absorption capacity and porosity, which are in line with the conditions of biological experiments. The effect of induced differentiation of cells was the best when cultured alone. After direct contact between the two types of cells at 2D or 3D level, the induced differentiation of cells was inhibited to varying degrees, although they still showed osteogenesis and osteoclast. After the cells were induced by indirect contact culture, the effect of induced differentiation improved when compared with direct contact culture, although it was still not as good as that of single culture. On the whole, the effect of inducing differentiation at 3D level was the same as that at 2D level, and its relative gene expression and enzyme activity were higher than that in the control group. Hence the scaffold used in this study could induce osteogenesis as well as osteoclast, thereby rendering it more effective in inducing new bone formation.Conclusion: This method can be used to construct the model of 3D bone remodeling mechanism.