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Abstract Background Colorectal cancer (CRC) is one of the lethal cancers with a high mortality rate worldwide and understanding the mechanisms behind its progression is critical for improving patients’ prognosis and developing therapeutics. MiR-500a-3p has been demonstrated to be involved in the progression of several human cancers but its role in CRC remains unclear. The aim of this study is to uncover the expression pattern and mechanisms of action of miR-500a-3p during the CRC progression. Methods The expression of miR-500a-3p and Cyclin-dependent kinases 6 (CDK6) in 134 CRC tissues were tested by quantitative PCR (qPCR) and immunohistochemistry staining (IHC), respectively. The effect of miR-500a-3p on cell proliferation was explored in vitro and in vivo. The glycolysis of CRC cells was determined by Mass Spectrometry and Seahorse XF 96 Extracellular Flux Analyzer. A dual-luciferase reporter assay was performed to validate the relationship between miR-500a-3p and CDK6. Results miR-500a-3p was abnormally downregulated in CRC tissues and cell lines and was negatively associated with a worse prognosis. miR-500a-3p mimics impeded CRC cell proliferation in vitro and in vivo. miR-500a-3p inhibited glucose consumption, lactate and ATP production, and down-regulated the expression of hexokinase2 (HK2). In silico prediction combined with western blot and luciferase assay confirmed that CDK6 is a direct target of miR-500a-3p. Overexpression of CDK6 phenotypically rescued the inhibitory effect of miR-500a-3p on the proliferation and glycolysis of CRC cells. Conclusions Our study revealed a potential tumor-suppressive role of miR-500a-3p in CRC, specifically targeting CDK6 and inhibiting cancer cell proliferation and aerobic glycolysis, which may provide new insights into novel prognostic biomarkers and therapeutic targets for CRC.

As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. Here, the authors report a machine learning model using mass spectrometry-based liquid biopsy data for pan-cancer screening and classification.

The tumor microenvironment (TME) plays a crucial role in tumor progression and metastasis. However, the immune phenotypes of colorectal cancer (CRC) and the underlying immune escape mechanism have not been studied sufficiently. A total of 1802 and 619 CRC samples from the microarray and TCGA cohorts were enrolled, respectively. The ssGSEA algorithm and unsupervised clustering were used for TME cell infiltration speculation and immune phenotype recognition in the above cohorts. A total of 447 samples from Zhongshan Hospital were collected for validation. Immunohistochemistry was performed in this cohort to quantify TME cell infiltration. The single-cell RNA-seq (scRNA-seq) data of 252,940 cells from 60 CRC samples was analyzed for further mechanistic exploration. CRC samples can be classified into three distinct immune phenotypes. Subtype 1, the immune-active subtype, was characterized by high infiltration of activated adaptive immune cells. Subtype 2, the immune-desert subtype, featured high tumor purity and low infiltration of immune and stromal cells. Subtype 3, the stroma-rich subtype, had high infiltration of stromal cells. The stroma-rich subtype conferred a significantly worse prognosis. The three subtypes had different immune escape mechanisms. The immune-active subtype has the highest immune checkpoint expression level. In comparison, the immune-desert subtype had the lowest immunogenicity and defective antigen presentation. The stroma-rich subtype lacked activated immune cells. In conclusion, distinct immune phenotypes and immune escape mechanisms may provide inspiration and direction for further research on CRC immunotherapy.

Abstract Backgrounds Cancer-related mortality in patients with colorectal cancer (CRC) is predominantly caused by development of colorectal liver metastases (CLMs). How to screen the sensitive chemotherapy and targeted therapy is the key element to improve the prognosis of CLMs patients. The study aims to develop patient-derived organoids-based xenografted liver metastases (PDOX-LM) model of CRC, to recapitulate the clinical drug response. Methods We transplanted human CRC primary tumor derived organoids in murine spleen to obtain xenografted liver metastases in murine liver. Immunohistochemistry (IHC) staining, whole-exome and RNA sequencing, and drug response testing were utilized to identify the homogeneity in biological and genetic characteristics, and drug response between the PDOX-LM models and donor liver metastases. Results We successfully established PDOX-LM models from patients with CLMs. IHC staining showed that positive expression of CEA, Ki67, VEGF, FGFR2 in donor liver metastases were also well preserved in matched xenografted liver metastases. Whole-exon sequencing and transcriptome analysis showed that both xenografted and donor liver metastases were highly concordant in somatic variants (≥ 0.90 frequency of concordance) and co-expression of driver genes (Pearson’s correlation coefficient reach up to 0.99, P = 0.001). Furthermore, drug response testing showed that the PDOX-LM models can closely recapitulated the clinical response to mFOLFOX6 regiments. Conclusions This PDOX-LM model provides a more convenient and informative platform for preclinical testing of individual tumors by retaining the histologic and genetic features of donor liver metastases. This technology holds great promise to predict treatment sensitivity for patients with CLMs undergoing chemotherapy.

Background: Long noncoding RNAs (LncRNA) lead a vital role in colorectal cancer (CRC) development. The infiltrating CD8+ T cell is the main target of immunotherapy. Our study aimed to figure out the potential mechanism of lncRNAs regulating the function of CD8+ T cells in CRC. Methods: We collected bulk RNA-seq, miRNA-seq, and single-cell RNA-seq (scRNA-seq) data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The cibersort algorithm and correlation analysis were used to estimate the abundance of CD8+ T cells and screened out the most relevant lncRNAs. We used scRNA-seq data to identify the main cell lncRNA expressed. Furthermore, one competing endogenous RNA (ceRNA) network focusing on the potential mechanism of lncRNA-derived CD8+ T cell infiltration was constructed. We established a co-culture system to assess the immunosuppressive function of the lncRNA. And we evaluated the effects of the lncRNA on CD8+ T cell cytotoxicity by flow cytometry, qPCR, and clone formation assay. Results: Three CD8+ T cell infiltration-related lncRNAs were identified, and LINC00657 was expressed mainly in tumor cells, negatively associated with CD8+ T cell infiltration. Hsa-miRNA-1224-3p and hsa-miRNA-338-5p and SCD, ETS2, UBE2H, and YY1 were identified to construct the ceRNA network. Immunosuppression-related tumor marker CD155 was proved to be positively correlated with LINC00657 and mRNAs in the ceRNA network. In addition, we proved that LINC00657 could impair the cytotoxicity of CD8+ T cells, and its expression was positively associated with CD155 in vitro. Conclusions: We successfully constructed an lncRNA-derived CD8+ T cell infiltration ceRNA network in CRC. LINC00657 may play a leading role in the CRC immune escape and could be a novel immunotherapy target.

The molecular classification of patients with colon cancer is inconclusive. The gene set enrichment analysis (GSEA) of dysregulated genes among normal and tumor tissues indicated that the cell cycle played a crucial role in colon cancer. We performed univariate Cox regression analysis to find out the prognostic-related genes, and these genes were then intersected with cell cycle-associated genes and were further recognized as prognostic and cell cycle-associated genes. Unsupervised non-negative matrix factorization (NMF) clustering was performed based on cell cycle-associated genes. Two subgroups were identified with different overall survival, clinical features, cell cycle enrichment profile, and mutation profile. Through nearest template prediction (NTP), the molecular classification could be effectively repeated in the original data set and validated in several independent data sets indicating that the classification is highly repeatable. Furthermore, we constructed two prognostic signatures in two subgroups, respectively. Our molecular classification based on cell cycle may provide novel insight into the treatment and the prognosis of colon cancer.

Colorectal cancer is a major cause of death worldwide, and the identification of new diagnostic and prognostic biomarkers is crucial to develop new strategies to avoid colorectal cancer-related deaths. Small nuclear ribonucleoprotein polypeptide N (SNRPN) is an imprinted gene that plays an important role in various neurodevelopmental disabilities. In this study, SNRPN was highly expressed in colorectal cancer tissues and involved in the progression of this disease. Immunohistochemistry analysis of 1,310 colorectal cancer tissue samples showed that SNRPN highly expressed in cancer tissues than in adjacent tissues and was mainly localized in the nucleus. Clinical pathological factor analysis demonstrated that higher expression of SNRPN was significantly associated with larger tumor size, location of the tumor on the left-sided colon, neural invasion, and distant metastasis. Univariate and multivariate analyses showed that SNRPN expression was an independent risk factor for survival, with high expression levels indicating worse overall survival. Both in vitro and in vivo experiments confirmed that high expression of SNRPN was associated with tumor proliferation, cell cycle, and metastasis. Knocking down SNRPN blocked the cell cycle at the G2/M phase transition and promoted tumor cell apoptosis, inhibiting the progression of colorectal cancer. To explore the up-steam of SNRPN, we found by luciferase reporter assay and chromosomal immunoprecipitation assay that E2F8 was a transcriptional regulator up-steam of SNRPN in colorectal cancer. Systematic studies of SNRPN will help us discover new regulatory molecules and provide a theoretical basis for finding new molecular targets for this disease.

Many genes and mutations have been reported for colorectal cancer (CRC); however, very few have been associated with colorectal cancer liver metastasis (CRLM). We performed gene expression profiling experiments to identify genetic markers for CRLM and elucidate the molecular mechanisms. Microarray experiments were performed on CRC primary tumor samples with or without liver metastasis (LM) using the Affymetrix U133 plus 2.0 GeneChip Array. A new identified gene-scinderin (SCIN) was overexpressed with synchronous LM at both the RNA level evaluated with quantitative real-time PCR and protein level evaluated with immunohistochemistry and also with short overall survival analyzed with Kaplan-Meier method. With multivariate analysis indicated that SCIN served as an independent poor prognostic predictor for CRC patients. Disease-free survival was also significantly lower in SCIN overexpressing CRC patients with metachronous LM. In addition, SCIN knockdown significantly reduced cell proliferation, induced cell cycle arrest, and promoted the expression of some cell cycle apoptosis-related protein. Moreover, the DIAPH1, STAT3, CDK2, CDK4, and EGFR levels were downregulated, whereas CDKN2B and COL4A1 were upregulated in DLD-1-shSCIN cells by microarray analysis compared with DLD-1 shCon cells. These findings revealed that SCIN may serve as an important predictor of CRLM and poor outcome for CRC patients. SCIN may be a potential therapeutic target in human CRC. However, translation of its roles into clinical practice will require further investigation and additional experimental validation.

Golden2-like (GLK) transcription factors are members of the GARP family of Myb transcription factors with an established relationship to chloroplast development in the plant kingdom. In the last century, Golden2 was proposed as a second golden producing factor and identified as controlling cellular differentiation in maize leaves. Then, GLKs were also found to play roles in disease defense and their function is conserved in regulating chloroplast development. Recently, research on GLKs has rapidly increased and shown that GLKs control chloroplast development in green and non-green tissues. Moreover, links between phytohormones and GLKs were verified. In this mini-review, we summarize the history, conservation, function, potential targets and degradation of GLKs.

Currently, no published studies have compared the clinical outcomes of the medial-to-lateral approach (MA) and lateral-to-medial approach (LA) for open right hemicolectomy. Thus, the present study aimed to assess whether one of these approaches has any potential benefits over the other.A retrospective study was performed of all patients who underwent open right hemicolectomy with pathologically confirmed disease who met the eligibility criteria between June 2008 and June 2012. The population was divided into an MA group and an LA group by propensity scoring. We compared patient demographic and clinical characteristic variables between the two groups and assessed short-term and long-term outcomes.A total of 450 patients (MA, n = 150; LA, n = 300) were evaluated. The operation time (MA,138.4 minutesvs.LA,166.2 minutes; P < .05) and blood loss (MA,52.0mL vs. LA,62.6mL; P < .05)were significantly lower in the MA group. No differences in the number of harvested lymph nodes and oncologic outcomes were observed between the two groups. Further subgroup analysis for stage III colon cancer revealed that the MA group had significantly more retrieved lymph nodes (MA,18.8vs. LA,16.0; P = .028). There were no differences in other variables between the two groups.The MA reduced operative time and blood loss compared with the LA. We thus concluded that the MA provided short-term benefits compared with the LA in open right hemicolectomy for right-sided colon cancer.

Nitrogen (N) is an essential nutrient for plant growth, and most plants absorb it as nitrate. AtNRG2 has been reported to play an important role in nitrate regulation. In this study, we investigated the functions of AtNRG2 family members of Arabidopsis thaliana and maize in nitrate signalling and metabolism. Our results showed that both AtNRG2.10 and AtNRG2.15 regulated nitrate signalling and metabolism. Overexpression of AtNRG2.11 (AtNRG2) could promote plant growth and improve nitrogen use efficiency (NUE). In addition, the maize genome harbors 23 ZmNRG2 members. We detected the expression of these genes treated with nitrate and the expression of four genes was strongly induced with ZmNRG2.7 having the highest levels. Overexpression of ZmNRG2.7 in the atnrg2 mutant could restore the defects of atnrg2, suggesting that ZmNRG2.7 is involved in nitrate signalling and metabolism. Moreover, the overexpression lines of ZmNRG2.7 showed increased biomass and NUE. These findings demonstrate that at least a part of NRG2 family genes in Arabidopsis and maize regulate nitrate signalling and provide a molecular basis for improving the NUE of crops. [ABSTRACT FROM AUTHOR]

A 29-year-old man visited Zhongshan Hospital, Fudan University in December 2021. The patient presented with recurrent coughing, sputum, and wheezing, high level of serum total IgE, positive aspergillus fumigatus-specific IgE and extremely severe mixed ventilatory dysfunction. These features and thoracic CT results scan showed bronchiectasis and allergic bronchopulmonary aspergillosis. In consideration of his clinical characteristics, including low levels of fractional exhaled nitric oxide (FeNO), and nasal nitric oxide (nNO), persistent cough after birth, consanguineous marriage of his parents, etc. we ratiocinated a possibility of hereditary diseases, especially primary ciliary dyskinesia (PCD). From this perspective, whole exome sequencing (WES) was performed and the diagnosis of PCD was ultimately confirmed.

Introduction: Investigation on virus-host interaction may provide new clues for antitumor immunotherapy. Case Presentation: In this case report, we describe an unusual case of B-cell non-Hodgkin lymphoma in an aged woman who recovered following SARS-COV-2 infection. We discuss the case and suggest that virus induced cross-reactivity against tumor account for the remission. Conclusion: Mapping epitope characteristics on B cell non-Hodgkin lymphoma antigen and on SARS-COV-2 antigen may provide much needed information for antigen based antitumor immune therapy in the future.

IntroductionThis meta-analysis examined the relationship between age-related hearing loss (ARHL) and depression in older adults, and further explored whether this relationship is moderated by age and gender.MethodsWe searched in 4 English databases: PubMed, Embase, Web of Science, and Cochrane Library. Ultimately, we identified 9 studies, involving 3 cohort studies and 6 cross-sectional studies. We used Hedges' g as the effect size, and all pooled analyses were performed using random-effects models.ResultsARHL patients had higher depressive symptom scores than non-ARHL older adults (g = 0.52). When divided into subgroups based on study type, a large effect size was demonstrated in the cross-sectional study group (g = 0.68) and was not statistically different in the cohort study group (g = 0.06). Meta-regression results showed that the effect size of depression in older adults with ARHL was significantly associated with the percentage of females (t = 5.97, p = 0.000) and not significantly associated with age (t = 0.94, p = 0.364).ConclusionsPatients with ARHL are more likely to be depressed than older adults with normal hearing, and this relationship is influenced by the gender of the patients.

Subgingival dental defects are common in clinical practice among patients with deep dental caries and dental fractures. These defects commonly accompany lesions involving marginal alveolar bone loss and gingival recession, and their clinical management is challenging. Restoring gingival adhesion and activating the regeneration of periodontal tissue are important for a better prognosis in these cases. However, there is no effective resin material for complex restorations involving the destruction of subgingival tissue. To achieve greater biocompatibility, resins are generally modified with bioactive particles that can release specific components. Surface prereacted glass ionomer (S-PRG) is a novel glass particle characterized by a three-layered structure and the release of multiple ions with bioactive potential. Therefore, in this study, we incorporated S-PRG filler into resin-based composites to investigate their effectiveness in the restoration of subgingival defects. Resin composites containing 0, 10, 30, 50, or 70 wt% S-RPG filler were fabricated and formed into material discs, where a commercial resin composite served as the control group. The microstructure and elemental distribution were characterized by scanning electronic microscopy and energy-dispersive spectroscopy. The resin composites containing 50 or 70 wt% S-PRG fillers exhibited comprehensively better physicochemical properties, including flexural modulus, compressive strength, and water sorption. The ion release profile and environmental pH of the resins were measured with material extracts. Periodontal ligament stem cells were considered as seed cells that harbored great potential for periodontal regeneration. Cellular experiments suggested that S-PRG promotes cell proliferation and adhesion, induces cell migration, and stimulates vascularized osteogenesis. The feasibility of using S-PRG-containing resin composite to rectify subgingival dental defects was confirmed in vivo. After restoration with the S-PRG-filled resin material, intact epithelial tissue adhered to the resin surface with no visible inflammation. In conclusion, S-PRG-filled resin composites showed some biocompatibility as an alternative material for clinical applications.

Tumors constitute a significant health concern for humans, and PD-1 and CTLA-4 monoclonal antibodies have been proven effective in cancer treatment. Some researchers have identified that the combination of PD-1 and CTLA-4 dual blockade demonstrates superior therapeutic efficacy. However, the development of PD-1/CTLA-4 bispecific antibodies faces challenges in terms of both safety and efficacy. The present study discloses a novel PD-1/CTLA-4 bispecific antibody, designated as SH010. Experimental validation through surface plasmon resonance (SPR) confirmed that SH010 exhibits favorable binding activity with both PD-1 and CTLA-4. Flow cytometry analysis demonstrated stable binding of SH010 antibody to CHOK1 cells overexpressing human or cynomolgus monkey PD-1 protein and to 293F cells overexpressing human or cynomolgus monkey CTLA-4 protein. Moreover, it exhibited excellent blocking capabilities in protein binding between human PD-1 and PD-L1, as well as human CTLA-4 and CD80/CD86. Simultaneously, in vitro experiments indicate that SH010 exerts a significant activating effect on hPBMCs. In murine transplant models of human prostate cancer (22RV1) and small cell lung cancer (NCI-H69), administration of varying concentrations of the bispecific antibody significantly inhibits tumor growth. MSD analysis revealed that stimulation of hPBMCs from three different donors with SH010 did not induce the production of cytokine release syndrome. Furthermore, Single or repeated intravenous administrations of SH010 in cynomolgus monkeys show favorable systemic exposure without noticeable drug accumulation or apparent toxicity. In conclusion, SH010 represents a novel cancer therapeutic drug poised to enter clinical trials and obtain market approval.

BackgroundN6-methyladenosine (m6A) has been shown to mediate ferroptosis but its role in atherosclerosis (AS) is unclear.MethodsDifferentially expressed m6A-associated ferroptosis-related genes (DE-m6A-Ferr-RGs) were obtained using differential expression analysis and Pearson correlation analysis. Weighted gene co-expression network analysis (WGCNA) was also performed. The intersection of the module genes and the DE-m6A-Ferr-RGs were recorded as candidate m6A-Ferr-related signature genes. Finally, the m6A-Ferr-related signature genes were screened using least absolute shrinkage and selection operator (LASSO) analysis. Expression validation, receiver operating characteristic ( mapping, and immune correlation analysis were also performed based on the m6A-Ferr-related signature genes. The expression of m6A-Ferr-related signature genes was further validated using a real-time polymerase chain reaction (RT-qPCR).ResultsIn total, 6,167 differentially expressed genes were intersected with 24 m6A- and 259 ferroptosis-related genes, respectively, resulting in 113 DE-m6A-Ferr-RGs obtained using Pearson’s correlation analysis. The module genes obtained from the WGCNA and the 113 DE-m6A-Ferr-RGs were intersected to obtain 48 candidate m6A-Ferr-related signature genes. LASSO analysis was performed and six m6A-Ferr-related signature genes were screened. In addition, the area under the curve values of all six m6A-Ferr-related signature genes were greater than 0.7, indicating that they had potential diagnostic value. Furthermore, the RT-qPCR results revealed that the expression of SLC3A2, NOX4, and CDO1 was consistent with the transcriptome level. Moreover, there was a significant difference in two types of immune cells between the AS and control groups. Naive B cells, CD8+ T cells, regulatory T cells, and activated natural killer cells were positively correlated with CDO1 and NOX4 but negatively correlated with ATG7, CYBB, and SLC3A2.ConclusionIn total, three m6A-Ferr-related signature genes (NOX4, CDO1, and SLC3A2) were obtained through a series of bioinformatics analyses and an RT-qPCR.

Introduction: The treatment of COVID-19 patients, especially high-risk patients, remains a large challenge. Glucocorticoids have been accepted as effective medicines for severe COVID-19. However, the glucocorticoid usage guidelines do not cover all the indications for high-risk patients. Objective: To identify more effective treatments for high-risk patients with COVID-19, this retrospective study analyzed routine epidemiological, clinical, and laboratory data from 33 high-risk patients with COVID-19 in Beijing Gobroad Boren Hospital, Beijing, China, most of whom responded well to treatment. Methods: Severe acute respiratory syndrome coronavirus-2 infection was confirmed via real-time reverse transcriptase polymerase chain reaction assays. Outcome measures such as duration of mechanical ventilation, intensive care unit length of stay, and 28-day mortality were analyzed. Patients were divided into two groups: mild to moderate COVID-19 ( n = 26) and severe COVID-19 ( n = 7). Chest computed tomography images were used to guide methylprednisolone administration or withdrawal. Results: Upon intensive care unit admission, 12.1% of patients were mechanically ventilated with an average partial pressure of oxygen/fraction of inspired oxygen(PaO 2 /FiO 2 ) ratio of 279 ± 146. No coinfections with other endemic viruses were observed. The duration of mechanical ventilation was 16 days (interquartile range: 8–28); the intensive care unit length of stay was 11 (interquartile range: 2–33) days; and the 28-day total mortality was 3.0%. Conclusion: Multivariate regression analysis revealed that low-dose, timely methylprednisolone administration was associated with a lower severe COVID-19 rate and mortality in high-risk patients. For high-risk patients, once there are ground-glass opacities (GGO) in the computed tomography image, continuous and low-dose methylprednisolone administration promotes inflammation remission and protects them from severe COVID-19 or mortality.

Background Diagnosis of the cause of cerebral thrombi is vital for recurrence prevention but also challenging. The presence of the microbiome has recently been confirmed in thrombus, suggesting a novel approach to distinguish cerebral thrombi of different origins. However, little is known about whether there is heterogeneity in microbiological colonization of cerebral thrombi of different sources. Methods and Results Forty patients experiencing acute ischemic stroke were included and clinical data were collected. Metagenomic next‐generation sequencing was adopted to detect bacterial and genomic signatures of human cerebral thrombi samples. We found similar species diversity between the large‐artery atherosclerosis thrombi and cardioembolic thrombi but different species composition and distribution of cerebral thrombus microbiota. Compared with the group with cardioembolism, the group with large‐artery atherosclerosis showed a significantly higher relative abundance of Ralstonia insidiosa among the top 10 bacterial species in cerebral thrombi. Twenty operational taxonomy units were correlated with 11 clinical indicators of ischemic stroke. The Gene Ontology enrichment analysis revealed 9 different enriched biological processes (translation and carbohydrate metabolic process, etc). The enriched Kyoto Encyclopedia of Genes and Genomes pathways included ribosome, butanoate metabolism, and sulfur metabolism. Conclusions This study, based on the approach of metagenomic next‐generation sequencing, provides a diagnostic microbiological method to discriminate individuals with cardioembolic thrombi from those with large‐artery atherosclerosis thrombi with human cerebral thrombi samples. Our findings provide a fresh perspective on microbial heterogeneity of cerebral thrombi and demonstrate biological processes and pathway features of cerebral thrombi.

Abstract Intercropping with Pleurotus ostreatus has been demonstrated to increase the tea yield and alleviate soil acidification in tea gardens. However, the underlying mechanisms remain elusive. Here, high-throughput sequencing and Biolog Eco analysis were performed to identify changes in the community structure and abundance of soil microorganisms in the P. ostreatus intercropped tea garden at different seasons (April and September). The results showed that the soil microbial diversity of rhizosphere decreased in April, while rhizosphere and non-rhizosphere soil microbial diversity increased in September in the P. ostreatus intercropped tea garden. The diversity of tea tree root microorganisms increased in both periods. In addition, the number of fungi associated with organic matter decomposition and nutrient cycling, such as Penicillium, Trichoderma, and Trechispora, was significantly higher in the intercropped group than in the control group. Intercropping with P. ostreatus increased the levels of total nitrogen (TN), total phosphorus (TP), and available phosphorus (AP) in the soil. It also improved the content of secondary metabolites, such as tea catechins, and polysaccharides in tea buds. Microbial network analysis showed that Unclassified_o__Helotiales, and Devosia were positively correlated with soil TN and pH, while Lactobacillus, Acidothermus, and Monascus were positively correlated with flavone, AE, and catechins in tea trees. In conclusion, intercropping with P. ostreatus can improve the physical and chemical properties of soil and the composition and structure of microbial communities in tea gardens, which has significant potential for application in monoculture tea gardens with acidic soils.

Abstract A flavor precursor of 4-methyloxybenzyl-2, 3, 4, 6-tetra-O-acetyl-β-d-glucopyranoside (MBGL) was synthesized via a modified Koenigs–Knorr reaction. The thermal decomposition behaviour and pyrolysis intermediate products of the glycoside were studied by simultaneous thermogravimetric/differential thermal analysis (TG/DTA) and synchrotron vacuum ultraviolet (VUV) photoionization mass spectrometry (PIMS). TG/DTA results showed that the largest mass loss rate appeared at a T p of 246.7 °C. PIMS was used to identify the pyrolysis products of MBGL at 300 °C, 500 °C and 700 °C, respectively. The experimental apparatus had some advantages in real-time analysis and fewer secondary reactions. Some important pyrolysis intermediates, such as the ions of the 4-methyloxybenzyl group at m/z 121 and the glycone moiety at m/z 347, were detected by PIMS. The results indicate that the MBGL was probably showed a different pyrolysis way compared with the other glycosides. This work reports a useful application of synchrotron VUV PIMS in a thermal decomposition study of glycoside flavor precursors.

Abstract Background Lupus nephritis (LN) is the most common and severe clinical manifestation of systemic lupus erythematosus (SLE). N6-methyladenosine (m6A) is a reversible RNA modification and has been implicated in various biological processes. However, the roles of m6A regulators in LN are not fully demonstrated. Methods We downloaded the kidney tissue transcriptome dataset of LN patients and normal controls from the GEO database and extracted the expression levels of m6A regulators. We constructed and compared Random Forest (RF) and Support Vector Machine (SVM) models, and subsequently selected featured genes to develop nomogram models. The m6A subtypes were identified based on significantly differentially expressed m6A regulators, and the m6A gene subtypes were identified based on m6A-associated differential genes, and the two m6A modification patterns were comprehensively evaluated. Results We obtained the GSE32591 and GSE112943 datasets from the GEO database, including 78 LN samples and 36 normal control samples. We extracted the expression levels of 20 m6A regulators. By RF analysis we identified 7 characteristic m6A regulators and constructed nomogramh models with these 7 genes. We identified two m6A subtypes based on these seven important m6A regulators, and the immune cell infiltration levels of the two subtype clusters were significantly different. We identified two more m6A gene subtypes based on m6A-associated DEGs. We calculated the m6A scores using the principal component analysis (PCA) algorithm and found that the m6A scores of m6A cluster A and gene cluster A were lower than those of m6A cluster B and gene cluster B. In addition, we found that the levels of inflammatory factors were also significantly different between m6A clusters and gene clusters. Conclusion This study confirms that m6A regulators are involved in the LN process through different modes of action and provide new diagnostic and therapeutic targets for LN.

Communities or neighborhoods are specific places in the research field of place identity that links between environment and psychology to address the sense of belonging as one of crucial human needs. This article explores the community identity in Chinese urban communities to investigate differences between sense of communities, and community satisfaction. Since 1980s, gated communities (Xiaoqu) are the dominant form of residential development in urban China and sometimes have the same boundary as the community (Shequ). Thus, this article sheds light on different understanding of gated communities in and outside of China. It is approached via deductive research to assess four specific hypotheses based on the concepts of communities, neighborhoods and gated communities. Four gated communities from Suzhou Industrial Park in China are used as study sites, where primary data was collected and then analyzed via multiple linear regression model and logistic regression model. Interestingly, the finding shows that having an active homeowners’ committee, which is considered as a socio-political force, is negatively associated with a sense of community. In addition, representation is positively associated with community identity in general. The findings imply that property management fees play an important role in residents’ community identity. In addition, the finding also supports that sense of community is a social rather than a physical construction.

Abstract Background Severe asthma places a large burden on patients and society. The characteristics of patients with severe asthma in the Chinese population remain unclear. Methods A retrospective review was conducted in patients with severe asthma. Demographic and clinical data were collected. Patients were grouped according to phenotypes in terms of exacerbations, body mass index (BMI) and fixed airway obstruction (FAO) status, and the characteristics of different groups were compared. Comorbidities, factors that influence asthma phenotypes, were also analyzed in the study. Results A total of 228 patients with severe asthma were included in our study. They were more likely to be overweight or obese. A total of 41.7% of the patients received GINA step 5 therapy, and 43.4% had a history of receiving regular or intermittent oral corticosteroids (OCS). Severe asthmatic patients with comorbidities were prone to have more asthma symptoms and decreased quality of life than patients without comorbidities. Patients with exacerbations were characterized by longer duration of asthma, poorer lung function, and worse asthma control. Overweight or obese patients tended to have more asthma symptoms, poorer lung function and more asthma-related comorbidities. Compared to patients without FAO, those in the FAO group were older, with longer duration of asthma and more exacerbations. Conclusion The existence of comorbidities in patients with severe asthma could result in more asthma symptoms and decreased quality of life. Patients with exacerbations or with overweight or obese phenotypes were characterized by poorer lung function and worse asthma control. Patients with FAO phenotype tended to have more exacerbations.

Abstract Background This study explored the effects of attention shifting on Chinese children’s word reading. Objective The sample consisted of 87 fourth-grade children from Shaoxing City, China. Methods The students completed measures of the attention shifting task, reading accuracy test, reading fluency test, and rapid automatized naming test. Results The results showed that reading fluency was significantly correlated with attention shifting scores, specifically with tag1 and tag6 (ps

Abstract Embryonic stem cell (ESC)-derived epitopes can act as therapeutic tumor vaccines against different types of tumors Jin (Adv Healthc Mater 2023). However, these epitopes have poor immunogenicity and stimulate insufficient CD8+ T cell responses, which motivated us to develop a new method to deliver and enhance their effectiveness. Bacterial outer membrane vesicles (OMVs) can serve as immunoadjuvants and act as a delivery vector for tumor antigens. In the current study, we engineered a new OMV platform for the co-delivery of ESC-derived tumor antigens and immune checkpoint inhibitors (PD-L1 antibody). An engineered Staphylococcal Protein A (SpA) was created to non-specifically bind to anti-PD-L1 antibody. SpyCatcher (SpC) and SpA were fused into the cell outer membrane protein OmpA to capture SpyTag-attached peptides and PD-L1 antibody, respectively. The modified OMV was able to efficiently conjugate with ESC-derived TAAs and PD-L1 antibody (SpC-OMVs + SpT-peptides + anti-PD-L1), increasing the residence time of TAAs in the body. The results showed that the combination therapy of ESC-based TAAs and PD-L1 antibody delivered by OMV had significant inhibitory effects in mouse tumor model. Specifically, it was effective in reducing tumor growth by enhancing IFN-γ-CD8+ T cell responses and increasing the number of CD8+ memory cells and antigen-specific T cells. Overall, the new OMV delivery system is a versatile platform that can enhance the immune responses of ESC-based TAA cancer vaccines. Graphical Abstract

Abstract Background Lymphangioleiomyomatosis (LAM) is a rare disease which is easily misdiagnosed. Vascular endothelial growth factor D (VEGF-D), as the most common biomarker, however, is not so perfect for the diagnosis and severity assessment of LAM. Materials and methods The isobaric tags for relative and absolute quantitation (iTRAQ)-based method was used to identify a cytoskeleton protein, moesin. 84 patients with LAM, 44 patients with other cystic lung diseases (OCLDs), and 37 healthy control subjects were recruited for collecting blood samples and clinical data. The levels of moesin in serum were evaluated by ELISA. The relationships of moesin with lymphatic involvement, lung function, and treatment decision were explored in patients with LAM. Results The candidate protein moesin was identified by the proteomics-based bioinformatic analysis. The serum levels of moesin were higher in patients with LAM [219.0 (118.7–260.5) pg/mL] than in patients with OCLDs (125.8 ± 59.9 pg/mL, P

IntroductionMicrobial community composition is closely associated with host disease onset and progression, underscoring the importance of understanding host–microbiota dynamics in various health contexts.MethodsIn this study, we utilized full-length 16S rRNA gene sequencing to conduct species-level identification of the microorganisms in the oral cavity of a giant panda (Ailuropoda melanoleuca) with oral malignant fibroma.ResultsWe observed a significant difference between the microbial community of the tumor side and non-tumor side of the oral cavity of the giant panda, with the latter exhibiting higher microbial diversity. The tumor side was dominated by specific microorganisms, such as Fusobacterium simiae, Porphyromonas sp. feline oral taxon 110, Campylobacter sp. feline oral taxon 100, and Neisseria sp. feline oral taxon 078, that have been reported to be associated with tumorigenic processes and periodontal diseases in other organisms. According to the linear discriminant analysis effect size analysis, more than 9 distinct biomarkers were obtained between the tumor side and non-tumor side samples. Furthermore, the Kyoto Encyclopedia of Genes and Genomes analysis revealed that the oral microbiota of the giant panda was significantly associated with genetic information processing and metabolism, particularly cofactor and vitamin, amino acid, and carbohydrate metabolism. Furthermore, a significant bacterial invasion of epithelial cells was predicted in the tumor side.DiscussionThis study provides crucial insights into the association between oral microbiota and oral tumors in giant pandas and offers potential biomarkers that may guide future health assessments and preventive strategies for captive and aging giant pandas.

Background In China, the prevalence of severe asthma with eosinophilic phenotype is rising, yet treatment options are limited. Mepolizumab is the first targeted biologic therapy for eosinophilic-driven disease in China. This study (clinicaltrials.gov identifier NCT03562195) evaluated efficacy and safety of mepolizumab in Chinese patients with severe asthma. Methods The phase III, multicentre, randomised, placebo-controlled, double-blind, parallel-group study enrolled patients aged ≥12 years with severe asthma, with two or more exacerbations in the previous year, and on inhaled corticosteroids plus at least one controller medication. Following a 1–4-week run-in, patients were randomised 1:1 to mepolizumab 100 mg or placebo subcutaneously every 4 weeks for 52 weeks. The primary end-point was annualised rate of clinically significant exacerbations (CSEs) through week 52. Secondary end-points were time to first CSE, frequency of CSEs requiring hospitalisation/emergency department visits or hospitalisation over 52 weeks, mean change in St George's Respiratory Questionnaire (SGRQ) total score and pre-bronchodilator forced expiratory volume in 1 s (FEV1) at week 52; safety was evaluated. Results The modified intention-to-treat population included 300 patients. At week 52 with mepolizumab versus placebo, annualised rate of CSEs was 65% lower (0.45 versus 1.31 events per year; rate ratio 0.35, 95% CI 0.24–0.50; p

The multifaceted nature of online rumors poses challenges to their identification and control. Current approaches to online rumor governance are evolving from fragmented management to collaborative efforts, emphasizing the proactive management of rumor propagation processes. This transformation considers diverse rumor types, the response behaviors of self-media and netizens, and the capabilities of regulatory bodies. This study proposes a multi-agent intervention model rooted in uncertainty theory to mitigate online rumor dissemination. Its empirical validation includes comparing three rumor categories and testing it against a single-agent model, highlighting the efficacy of collaborative governance. Quantitative assessments underscore the model’s utility in providing regulatory authorities with a robust theoretical framework for adaptive decision-making and strategy adjustments based on real-world conditions.

ABSTRACTBackground Dental caries is a chronic, multifactorial and biofilm-mediated oral bacterial infection affecting almost every age group and every geographical region. Streptococcus mutans is considered an important pathogen responsible for the initiation and development of dental caries. It produces exopolysaccharides in situ to promote the colonization of cariogenic bacteria and coordinate dental biofilm development.Objective The understanding of the regulatory mechanism of S. mutans biofilm formation can provide a theoretical basis for the prevention and treatment of caries.Design At present, an increasing number of studies have identified many regulatory systems in S. mutans that regulate biofilm formation, including second messengers (e.g. c-di-AMP, Ap4A), transcription factors (e.g. EpsR, RcrR, StsR, AhrC, FruR), two-component systems (e.g. CovR, VicR), small RNA (including sRNA0426, srn92532, and srn133489), acetylation modifications (e.g. ActG), CRISPR-associated proteins (e.g. Cas3), PTS systems (e.g. EIIAB), quorum-sensing signaling system (e.g. LuxS), enzymes (including Dex, YidC, CopZ, EzrA, lmrB, SprV, RecA, PdxR, MurI) and small-molecule metabolites.Results This review summarizes the recent progress in the molecular regulatory mechanisms of exopolysaccharides synthesis and biofilm formation in S. mutans.

Abstract Objective To investigated the influence of illness perceptions and other risk factors related to poor asthma control and quality of life in adult outpatients with asthma in China. Methods Patients with a confirmed asthma diagnosis were recruited from the outpatient clinic at Zhongshan Hospital, Fudan University in Shanghai. Sociodemographic, psychological, and asthma related variables were assessed in all participants. Patients’ illness perceptions, medication adherence, asthma control, and quality of life were assessed using validated questionnaires, such as the Brief Illness Perception Questionnaire, Medication Adherence Rating Scale (MARS-A), the Asthma Control Test, and the Mini Asthma Quality of Life Questionnaire. Multiple linear regressions and logistic regressions were used to examine the associations between illness perceptions, medication adherence behaviors, and disease outcome (i.e., asthma control and quality of life). Results A total of two hundred thirty-one (231) outpatients with asthma were included in this cross-sectional study, 80 of whom (34.6%) had asthma that was uncontrolled. Patients who perceived their life (β = − 0.197, p