Multi-omics analysis and experimental validation of the value of monocyte-associated features in prostate cancer prognosis and immunotherapy.

Background: Monocytes play a critical role in tumor initiation and progression, with their impact on prostate adenocarcinoma (PRAD) not yet fully understood. This study aimed to identify key monocyte-related genes and elucidate their mechanisms in PRAD. Method: Utilizing the TCGA-PRAD dataset, immune cell infiltration levels were assessed using CIBERSORT, and their correlation with patient prognosis was analyzed. The WGCNA method pinpointed 14 crucial monocyte-related genes. A diagnostic model focused on monocytes was developed using a combination of machine learning algorithms, while a prognostic model was created using the LASSO algorithm, both of which were validated. Random forest and gradient boosting machine singled out CCNA2 as the most significant gene related to prognosis in monocytes, with its function further investigated through gene enrichment analysis. Mendelian randomization analysis of the association of HLA-DR high-expressing monocytes with PRAD. Molecular docking was employed to assess the binding affinity of CCNA2 with targeted drugs for PRAD, and experimental validation confirmed the expression and prognostic value of CCNA2 in PRAD. Result: Based on the identification of 14 monocyte-related genes by WGCNA, we developed a diagnostic model for PRAD using a combination of multiple machine learning algorithms. Additionally, we constructed a prognostic model using the LASSO algorithm, both of which demonstrated excellent predictive capabilities. Analysis with random forest and gradient boosting machine algorithms further supported the potential prognostic value of CCNA2 in PRAD. Gene enrichment analysis revealed the association of CCNA2 with the regulation of cell cycle and cellular senescence in PRAD. Mendelian randomization analysis confirmed that monocytes expressing high levels of HLA-DR may promote PRAD. Molecular docking results suggested a strong affinity of CCNA2 for drugs targeting PRAD. Furthermore, immunohistochemistry experiments validated the upregulation of CCNA2 expression in PRAD and its correlation with patient prognosis. Conclusion: Our findings offer new insights into monocyte heterogeneity and its role in PRAD. Furthermore, CCNA2 holds potential as a novel targeted drug for PRAD.

Nano/micro flexible fiber and paper-based advanced functional packaging materials.

Recently, fiber-based and functional paper food packaging has garnered significant attention for its versatility, excellent performance, and potential to provide sustainable solutions to the food packaging industry. Fiber-based food packaging is characterized by its large surface area, adjustable porosity and customizability, while functional paper-based food packaging typically exhibits good mechanical strength and barrier properties. This review summarizes the latest research progress on food packaging based on fibers and functional paper. Firstly, the raw materials used for preparing fiber and functional paper, along with their physical and chemical properties and roles in food packaging, were discussed. Subsequently, the latest advancements in the application of fiber and paper materials in food packaging were introduced. This paper also discusses future research directions and potential areas for improvement in fiber and functional paper food packaging to further enhance their effectiveness in ensuring food safety, quality, and sustainability.

Predicting surgical efficacy and diagnosing histological inflammation: the clinical significance of prostate exosome proteins in benign prostatic hyperplasia.

Background: Benign prostatic hyperplasia (BPH) is one of the most common causes of lower urinary tract symptoms (LUTS) among the aging male population. Recent studies have shown that histological inflammation (HI) plays a significant role in BPH, with prostatic exosomal protein (PSEP) identified as a potential biomarker for prostate diseases. Therefore, this study aimed to explore the effect of HI on LUTS in patients with BPH, and to further explore the clinical value of PSEP as a diagnostic biomarker of BPH complicated with HI and whether PSEP could be used as an index to predict the improvement of LUTS after operation. Methods: This study was an open-label, cohort study. The study enrolled all patients who were clinical diagnosed as BPH with LUTS and prepared to receive operation of the prostate at the Department of Urology of the Second Hospital of Hebei Medical University. International Prostate Symptom Score (IPSS) were used to evaluate the LUTS of the BPH. And the enrolled patients were divided into four groups, including none, mild HI, moderate HI, and severe HI, based on postoperative pathological results. Then the relationships between HI and IPSS, the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), as well as PSEP were analyzed. Simple and multiple linear regression analyses were performed on the preoperative IPSS and the difference of IPSS before and after surgery was examined. SPSS software version 26 was used for statistical analysis and Prism 9.0 was used to make violin plots. Results: A total of 69 patients were enrolled in the study. The violin plot results indicated IPSS and NIH-CPSI scores exhibited significant increases in correlation with the severity levels of HI (P<0.001; P<0.001). Among BPH patients with total prostate-specific antigen (t-PSA) levels higher than 4.0 ng/mL, a significant correlation was observed between PSEP levels and HI (P=0.04). Besides, simple and multiple linear regression analysis showed that HI (P<0.001) or PSEP (P=0.03) was significantly associated with IPSS and improvement of LUTS, assessed by postoperative and preoperative IPSS differences. Conclusions: The study indicated that IPSS and PSEP (when t-PSA >4 ng/mL) were correlated with the severity of HI in patients with BPH. PSEP was linearly correlated with IPSS and the degree of reduction in IPSS after surgery. Consequently, PSEP may serve as a promising predictor for assessing surgical efficacy and diagnosing the severity of HI in patients with BPH.

Construction of composite self-assembly coating based on chitosan for enhancing the flame-retardant and antibacterial performances of cotton fabric.

In this work, the step-by-step dip-coating (SBS) method was used to effectively improve the drawback of LBL by reducing the construction of a multilayer polyelectrolyte. Bio-based flame retardants, phytic acid (PA), and chitosan (CS) were further self-assembly on the surface of cotton fabric treated by epichlorohydrin-modified aramid nanofibers (AEP), ionic liquid (IL), and Cu ion. The pure cotton fabric was immersed in each dipping liquid only once, improving fire safety and antibacterial performance. The treated cotton self-extinguished with a 59 mm char length in the vertical flammability test, and the limiting oxygen index (LOI) value increased from 18.5 % to 38.5 %. The result of the cone calorimeter test (CCT) revealed that the fire hazard of flame-retardant cotton noteworthy declined (e.g., ~44.1 % and 55.4 % decline in peak heat release rate (pHRR) and total heat release rate (THR)). Conspicuously, the treated cotton exhibited a remarkably inhibiting effect on E. coli and S. aureus activity. The cotton fabric after flame-retardant finishing exhibited excellent fire safety and antibacterial performance.

Identification of metastasis-related genes for predicting prostate cancer diagnosis, metastasis and immunotherapy drug candidates using machine learning approaches.

BACKGROUND: Prostate cancer (PCa) is the second leading cause of tumor-related mortality in men. Metastasis from advanced tumors is the primary cause of death among patients. Identifying novel and effective biomarkers is essential for understanding the mechanisms of metastasis in PCa patients and developing successful interventions. METHODS: Using the GSE8511 and GSE27616 data sets, 21 metastasis-related genes were identified through the weighted gene co-expression network analysis (WGCNA) method. Subsequent functional analysis of these genes was conducted on the gene set cancer analysis (GSCA) website. Cluster analysis was utilized to explore the relationship between these genes, immune infiltration in PCa, and the efficacy of targeted drug IC50 scores. Machine learning algorithms were then employed to construct diagnostic and prognostic models, assessing their predictive accuracy. Additionally, multivariate COX regression analysis highlighted the significant role of POLD1 and examined its association with DNA methylation. Finally, molecular docking and immunohistochemistry experiments were carried out to assess the binding affinity of POLD1 to PCa drugs and its impact on PCa prognosis. RESULTS: The study identified 21 metastasis-related genes using the WGCNA method, which were found to be associated with DNA damage, hormone AR activation, and inhibition of the RTK pathway. Cluster analysis confirmed a significant correlation between these genes and PCa metastasis, particularly in the context of immunotherapy and targeted therapy drugs. A diagnostic model combining multiple machine learning algorithms showed strong predictive capabilities for PCa diagnosis, while a transfer model using the LASSO algorithm also yielded promising results. POLD1 emerged as a key prognostic gene among the metastatic genes, showing associations with DNA methylation. Molecular docking experiments supported its high affinity with PCa-targeted drugs. Immunohistochemistry experiments further validated that increased POLD1 expression is linked to poor prognosis in PCa patients. CONCLUSIONS: The developed diagnostic and metastasis models provide substantial value for patients with prostate cancer. The discovery of POLD1 as a novel biomarker related to prostate cancer metastasis offers a promising avenue for enhancing treatment of prostate cancer metastasis.

Aging-Associated Metabolite Methylmalonic Acid Increases Susceptibility to Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by pulmonary fibroblast overactivation, resulting in the accumulation of abnormal extracellular matrix and lung parenchymal damage. Although the pathogenesis of IPF remains unclear, aging was proposed as the most prominent nongenetic risk factor. Previous studies have indicated that propionate metabolism undergoes reprogramming in the aging population, leading to the accumulation of the by-product methylmalonic acid (MMA). This study aims to explore alterations in propionate metabolism in IPF and the impact of the by-product MMA on pulmonary fibrosis. The present study revealed alterations in the expression of enzymes involved in propionate metabolism within IPF lung tissues, characterized by an increase in propionyl-CoA carboxylase and methylmalonyl-CoA epimerase expression, and a decrease in methylmalonyl-CoA mutase expression. Knockdown of methylmalonyl-CoA mutase, the key enzyme in propionate metabolism, in A549 cells induced a profibrotic phenotype and activated co-cultured fibroblasts. MMA exacerbated bleomycin-induced mouse lung fibrosis and induced a profibrotic phenotype in both epithelial cells and fibroblasts through activation of the canonical transforming growth factor-ß/Smad pathway. Overall, our findings unveil an alteration of propionate metabolism in IPF, leading to MMA accumulation, thus exacerbating lung fibrosis through promoting profibrotic phenotypic transitions via the canonical transforming growth factor-ß/Smad signaling pathway.

Genetically predicted asthma and the risk of abnormal spermatozoa.

Background: Several previous animal and human studies have found a strong association between asthma and spermatozoa quality, but whether these associations are causal or due to bias remains to be elucidated. Methods: We performed a two-sample Mendelian randomization (MR) analysis to assess the causal effect of genetically predicted asthma on the risk of abnormal spermatozoa. Asthma, childhood-onset asthma (COA), and adult-onset asthma (AOA) (sample sizes ranging from 327,670 to 408,442) were included as the exposures. Genetic information for abnormal spermatozoa was obtained from a genome-wide association study (GWAS) comprising 209,921 participants. In univariable MR (UVMR) analysis, the inverse variance weighted (IVW) method was conducted as the primary method, with the MR Egger and weighted median used as supplementary methods for causal inference. Sensitivity analyses, including the Cochran Q test, Egger intercept test, MR-PRESSO, and leave-one-out analysis, were performed to verify the robustness of the MR results. Multivariable MR (MVMR) was conducted to evaluate the direct causal effects of asthma on abnormal spermatozoa risk. Results: UVMR detected causal associations between genetically predicted asthma and an increased risk of abnormal spermatozoa (OR: 1.270, 95% CI: 1.045-1.545, p = 0.017). Moreover, we found that AOA (OR: 1.46, 95% CI: 1.051, 2.018, p = 0.024) has positive causal effects on the risk of abnormal spermatozoa rather than COA (p = 0.558). Sensitivity analysis found little evidence of bias in the current study (p > 0.05). MVMR further confirmed that asthma directly affected the risk of abnormal spermatozoa. Conclusion: Our MR study suggested that genetically predicted asthma could be associated with an increased risk of abnormal spermatozoa, and similar results were obtained in AOA. Further studies are warranted to explain the underlying mechanisms of this association and may provide new avenues for prevention and treatment.

Common immunological and prognostic features of lung and bladder cancer via smoking-related genes: PRR11 gene as potential immunotherapeutic target.

Smoking is a well-known risk factor for non-small-cell lung cancer (NSCLC) and bladder urothelial carcinoma (BLCA). Despite this, there has been no investigation into a prognostic marker based on smoking-related genes that could universally predict prognosis in these cancers and correlate with immune checkpoint therapy. This study aimed to identify smoking-related differential genes in NSCLC and BLCA, analyse their roles in patient prognosis and immune checkpoint therapy through subgroup analyses, and shed light on PRR11 as a crucial prognostic gene in both cancers. By examining PRR11 co-expressed genes, a prognostic model was constructed and its impact on immunotherapy for NSCLC and BLCA was evaluated. Molecular docking and tissue microarray analyses were conducted to explore the correlation between PRR11 and its reciprocal gene SPDL1. Additionally, miRNAs associated with PRR11 were analysed. The study confirmed a strong link between smoking-related genes, prognosis, and immune checkpoint therapy in NSCLC and BLCA. PRR11 was identified as a key smoking-associated gene that influences the efficacy of immune checkpoint therapy by modulating the stemness of these cancers. A prognostic model based on PRR11 co-expressed genes in BLCA was established and its prognostic value was validated in NSCLC. Furthermore, it was found that PRR11 regulates PDL1 via SPDL1, impacting immunotherapeutic efficacy in both cancers. The involvement of hsa-miR-200b-3p in the regulation of SPDL1 expression by PRR11 was also highlighted. Overall, the study elucidates that PRR11 modulates patient immunotherapy by influencing PDL1 expression through its interaction with SPDL1, with potential upstream regulation by hsa-miR-200b-3p.

Evaluating the predictive value of angiogenesis-related genes for prognosis and immunotherapy response in prostate adenocarcinoma using machine learning and experimental approaches.

Background: Angiogenesis, the process of forming new blood vessels from pre-existing ones, plays a crucial role in the development and advancement of cancer. Although blocking angiogenesis has shown success in treating different types of solid tumors, its relevance in prostate adenocarcinoma (PRAD) has not been thoroughly investigated. Method: This study utilized the WGCNA method to identify angiogenesis-related genes and assessed their diagnostic and prognostic value in patients with PRAD through cluster analysis. A diagnostic model was constructed using multiple machine learning techniques, while a prognostic model was developed employing the LASSO algorithm, underscoring the relevance of angiogenesis-related genes in PRAD. Further analysis identified MAP7D3 as the most significant prognostic gene among angiogenesis-related genes using multivariate Cox regression analysis and various machine learning algorithms. The study also investigated the correlation between MAP7D3 and immune infiltration as well as drug sensitivity in PRAD. Molecular docking analysis was conducted to assess the binding affinity of MAP7D3 to angiogenic drugs. Immunohistochemistry analysis of 60 PRAD tissue samples confirmed the expression and prognostic value of MAP7D3. Result: Overall, the study identified 10 key angiogenesis-related genes through WGCNA and demonstrated their potential prognostic and immune-related implications in PRAD patients. MAP7D3 is found to be closely associated with the prognosis of PRAD and its response to immunotherapy. Through molecular docking studies, it was revealed that MAP7D3 exhibits a high binding affinity to angiogenic drugs. Furthermore, experimental data confirmed the upregulation of MAP7D3 in PRAD, correlating with a poorer prognosis. Conclusion: Our study confirmed the important role of angiogenesis-related genes in PRAD and identified a new angiogenesis-related target MAP7D3.

Fat-soluble Vitamins and Lung Cancer: Where We Are?

Fat-soluble vitamins (vitamins A, D, E, and K) are vital substances for maintaining normal physiological functions in the body. In recent years, scholars have explored the relationship between fat-soluble vitamins and the wasting disease - lung cancer. In this paper, we review recent studies on fat-soluble vitamins and lung cancer to clarify the relevance and molecular mechanisms of various vitamins in lung cancer, and whether the levels of fat-soluble vitamins in the body and vitamin supplementation affect the development of lung cancer. Our review could facilitate the discovery of biomarkers, potential therapeutic targets in lung cancer, and anti-tumor adjuvant drugs, in addition to highlighting other new ideas in the prevention and treatment of lung cancer.

Dietary fiber and polyphenols from whole grains: effects on the gut and health improvements.

Cereals are the main source of energy in the human diet. Compared to refined grains, whole grains retain more beneficial components, including dietary fiber, polyphenols, proteins, vitamins, and minerals. Dietary fiber and bound polyphenols (biounavailable) in cereals are important active substances that can be metabolized by the gut microorganisms and affect the intestinal environment. There is a close relationship between the gut microbiota structures and various disease phenotypes, although the consistency of this link is affected by many factors, and the specific mechanisms are still unclear. Remodeling unfavorable microbiota is widely recognized as an important way to target the gut and improve diseases. This paper mainly reviews the interaction between the gut microbiota and cereal-derived dietary fiber and polyphenols, and also summarizes the changes to the gut microbiota and possible molecular mechanisms of related glycolipid metabolism. The exploration of single active ingredients in cereals and their synergistic health mechanisms will contribute to a better understanding of the health benefits of whole grains. It will further help promote healthier whole grain foods by cultivating new varieties with more potential and optimizing processing methods.

Repair and regeneration of the alveolar epithelium in lung injury.

Considerable progress has been made in understanding the function of alveolar epithelial cells in a quiescent state and regeneration mechanism after lung injury. Lung injury occurs commonly from severe viral and bacterial infections, inhalation lung injury, and indirect injury sepsis. A series of pathological mechanisms caused by excessive injury, such as apoptosis, autophagy, senescence, and ferroptosis, have been studied. Recovery from lung injury requires the integrity of the alveolar epithelial cell barrier and the realization of gas exchange function. Regeneration mechanisms include the participation of epithelial progenitor cells and various niche cells involving several signaling pathways and proteins. While alveoli are damaged, alveolar type II (AT2) cells proliferate and differentiate into alveolar type I (AT1) cells to repair the damaged alveolar epithelial layer. Alveolar epithelial cells are surrounded by various cells, such as fibroblasts, endothelial cells, and various immune cells, which affect the proliferation and differentiation of AT2 cells through paracrine during alveolar regeneration. Besides, airway epithelial cells also contribute to the repair and regeneration process of alveolar epithelium. In this review, we mainly discuss the participation of epithelial progenitor cells and various niche cells involving several signaling pathways and transcription factors.

Gut microbiome changes in mouse, Mongolian gerbil, and hamster models following Clostridioides difficile challenge.

Introduction: Clostridioides difficile infection (CDI), as well as its etiology and pathogenesis, have been extensively investigated. However, the absence of suitable CDI animal models that reflect CDI symptoms and the associated gut microbiome changes in humans has limited research progress in this field. Thus, we aimed to investigate whether Mongolian gerbils, which present a range of human pathological conditions, can been used in studies on CDI. Methods: In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing. Methods: In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing. Results: The results obtained showed that C. difficile colonized the gastrointestinal tracts of the three rodents, and after the C. difficile challenge, C57BL/6J mice did not manifest CDI symptoms and their intestines showed no significant pathological changes. However, the hamsters showed explosive intestinal bleeding and inflammation and the Mongolian gerbils presented diarrhea as well as increased infiltration of inflammatory cells, mucus secretion, and epithelial cell shedding in their intestinal tissue. Further, intestinal microbiome analysis revealed significant differences with respect to intestinal flora abundance and diversity. Specifically, after C. difficile challenge, the Firmicutes/Bacteroidetes ratio decreased for C57BL/6J mice, but increased significantly for Mongolian gerbils and hamsters. Furthermore, the abundance of Proteobacteria increased in all three models, especially in hamsters, while that of Verrucomicrobia only increased significantly in C57BL/6J mice and Mongolian gerbils. Our results also indicated that differences in the relative abundances of Lactobacillaceae and Akkermansia were primarily responsible for the observed differences in response to C. difficile challenge. Conclusion: Based on the observed responses to C. difficile challenge, we concluded for the first time that the Mongolian gerbil could be used as an animal model for CDI. Additionally, the taxa identified in this study may be used as biomarkers for further studies on CDI and to improve understanding regarding changes in gut microbiome in CDI-related diseases.

Shared and differing functional connectivity abnormalities of the default mode network in mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease (AD) and mild cognitive impairment (MCI) both show abnormal resting-state functional connectivity (rsFC) of default mode network (DMN), but it is unclear to what extent these abnormalities are shared. Therefore, we performed a comprehensive meta-analysis, including 31 MCI studies and 20 AD studies. MCI patients, compared to controls, showed decreased within-DMN rsFC in bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), precuneus/posterior cingulate cortex (PCC), right temporal lobes, and left angular gyrus and increased rsFC between DMN and left inferior temporal gyrus. AD patients, compared to controls, showed decreased rsFC within DMN in bilateral mPFC/ACC and precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC between DMN and right dorsolateral prefrontal cortex. Conjunction analysis showed shared decreased rsFC in mPFC/ACC and precuneus/PCC. Compared to MCI, AD had decreased rsFC in left precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC in right temporal lobes. MCI and AD share a decreased within-DMN rsFC likely underpinning episodic memory deficits and neuropsychiatric symptoms, but differ in DMN rsFC alterations likely related to impairments in other cognitive domains such as language, vision, and execution. This may throw light on neuropathological mechanisms in these two stages of dementia.

Multidimensional pan-cancer analysis of HSPA5 and its validation in the prognostic value of bladder cancer.

Endoplasmic reticulum (ER) stress-related genes are closely related to the occurrence, development, and immunotherapy response of tumors. This study provides a comprehensive assessment of HSPA5 from a pan-cancer perspective using multi-omics data. We analyzed the function of HSPA5 in multiple tumor types using multiple databases. Finally, immunohistochemistry was used to examine the relationship between HSPA5 expression in tissue microarrays from 100 patients with bladder cancer and the prognosis of patients with bladder cancer. Using the TCGA database, we were able to determine that HSPA5 is significantly elevated in a number of common malignancies and is linked with a bad prognosis. Cox regression analysis showed that the high expression of HSPA5 was correlated with OS, progression free survival (PFS), disease free survival (DFS), and disease special survival (DSS) of adrenocortical carcinoma (ACC). In addition, we discovered significant disparities in HSPA5 methylation and phosphorylation levels between various malignancies and normal tissues. HSPA5 expression was significantly correlated with the levels of infiltrating cells and immune checkpoint genes. HSPA5 is highly expressed in bladder cancer and patients with high HSPA5 expression have a poor prognosis. Our study provides a basis for further understanding of the role of ER stress-related gene HSPA5 in different tumor genesis and development. HSPA5 has also been shown to be a prognostic biomarker for bladder cancer patients.

Common and distinct cortical thickness alterations in youth with autism spectrum disorder and attention-deficit/hyperactivity disorder.

BACKGROUND: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders with overlapping behavioral features and genetic etiology. While brain cortical thickness (CTh) alterations have been reported in ASD and ADHD separately, the degree to which ASD and ADHD are associated with common and distinct patterns of CTh changes is unclear. METHODS: We searched PubMed, Web of Science, Embase, and Science Direct from inception to 8 December 2023 and included studies of cortical thickness comparing youth (age less than 18) with ASD or ADHD with typically developing controls (TDC). We conducted a comparative meta-analysis of vertex-based studies to identify common and distinct CTh alterations in ASD and ADHD. RESULTS: Twelve ASD datasets involving 458 individuals with ASD and 10 ADHD datasets involving 383 individuals with ADHD were included in the analysis. Compared to TDC, ASD showed increased CTh in bilateral superior frontal gyrus, left middle temporal gyrus, and right superior parietal lobule (SPL) and decreased CTh in right temporoparietal junction (TPJ). ADHD showed decreased CTh in bilateral precentral gyri, right postcentral gyrus, and right TPJ relative to TDC. Conjunction analysis showed both disorders shared reduced TPJ CTh located in default mode network (DMN). Comparative analyses indicated ASD had greater CTh in right SPL and TPJ located in dorsal attention network and thinner CTh in right TPJ located in ventral attention network than ADHD. CONCLUSIONS: These results suggest shared thinner TPJ located in DMN is an overlapping neurobiological feature of ASD and ADHD. This alteration together with SPL alterations might be related to altered biological motion processing in ASD, while abnormalities in sensorimotor systems may contribute to behavioral control problems in ADHD. The disorder-specific thinner TPJ located in disparate attention networks provides novel insight into distinct symptoms of attentional deficits associated with the two neurodevelopmental disorders. TRIAL REGISTRATION: PROSPERO CRD42022370620. Registered on November 9, 2022.

High-throughput mutagenesis and screening approach for the identification of drug-resistant mutations in the rifampicin resistance-determining region of mycobacteria.

Rifampicin is the most powerful first-line antibiotic for tuberculosis, which is caused by Mycobacterium tuberculosis. Although accumulating evidence from sequencing data of clinical M. tuberculosis isolates suggested that mutations in the rifampicin-resistance-determining region (RRDR) are strongly associated with rifampicin resistance, the comprehensive characterisation of RRDR polymorphisms that confer this resistance remains challenging. By incorporating I-SceI sites for I-SceI-based integrant removal and utilizing an L5 swap strategy, we efficiently replaced the integrated plasmid with alternative alleles, making mass allelic exchange feasible in mycobacteria. Using this method to establish a fitness-related gain-of function screen, we generated a mutant library that included all single-amino-acid mutations in the RRDR, and identified the important positions corresponding to some well-known rifampicin-resistance mutations (Q513, D516, S522, H525, R529, S531). We also detected a novel two-point mutation located in the RRDR confers a fitness advantage to M. smegmatis in the presence or absence of rifampicin. Our method provides a comprehensive insight into the growth phenotypes of RRDR mutants and should facilitate the development of anti-tuberculosis drugs.

Unveiling the role of YARS1 in bladder cancer: A prognostic biomarker and therapeutic target.

YARS is responsible for catalysing the binding of tyrosine to its cognate tRNA and plays a crucial role in basic biosynthesis. However, its biological functions in bladder cancer remains to be proven. We analysed variations in YARS1 expression and survival in bladder cancer using multiple data sets, including TCGA-BLCA, GSE13507 and bladder cancer-specific tissue microarrays. Furthermore, we explored the biological functions of YARS1 using transcriptome data. Our findings revealed a noteworthy correlation between YARS1 and immune infiltration in bladder cancer, as determined using the XCELL algorithm and single-cell analysis. In addition, we employed the TIDE algorithm to evaluate the responsiveness of different cohorts to immune checkpoint therapy. We investigated the regulatory associations between YARS1 and various aspects of bladder cancer, including senescence, ferroptosis and stemness. Finally, we established a ceRNA network that is directly linked to the overall prognosis, YARS1 can serve as a prognostic biomarker for bladder cancer; its interaction with MYC has implications for bladder cancer cell senescence, ferroptosis and stemness. Moreover, the identified ceRNA network has potential as a therapeutic target in bladder cancer.

Defense Regulatory Network Associated with circRNA in Rice in Response to Brown Planthopper Infestation.

The brown planthopper (BPH), Nilaparvata lugens (Stål), a rice-specific pest, has risen to the top of the list of significant pathogens and insects in recent years. Host plant-mediated resistance is an efficient strategy for BPH control. Nonetheless, BPH resistance in rice cultivars has succumbed to the emergence of distinct virulent BPH populations. Circular RNAs (circRNAs) play a pivotal role in regulating plant-environment interactions; however, the mechanisms underlying their insect-resistant functions remain largely unexplored. In this study, we conducted an extensive genome-wide analysis using high-throughput sequencing to explore the response of rice circRNAs to BPH infestations. We identified a total of 186 circRNAs in IR56 rice across two distinct virulence groups: IR-IR56-BPH (referring to IR rice infested by IR56-BPH) and IR-TN1-BPH, along with a control group (IR-CK) without BPH infestation. Among them, 39 circRNAs were upregulated, and 43 circRNAs were downregulated in the comparison between IR-IR56-BPH and IR-CK. Furthermore, in comparison with IR-CK, 42 circRNAs exhibited upregulation in IR-TN1-BPH, while 42 circRNAs showed downregulation. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the targets of differentially expressed circRNAs were considerably enriched in a multitude of biological processes closely linked to the response to BPH infestations. Furthermore, we assessed a total of 20 randomly selected circRNAs along with their corresponding expression levels. Moreover, we validated the regulatory impact of circRNAs on miRNAs and mRNAs. These findings have led us to construct a conceptual model that circRNA is associated with the defense regulatory network in rice, which is likely facilitated by the mediation of their parental genes and competing endogenous RNA (ceRNA) networks. This model contributes to the understanding of several extensively studied processes in rice-BPH interactions.

JAM3: A prognostic biomarker for bladder cancer via epithelial­mesenchymal transition regulation

Understanding the intricate relationship between prognosis, immune function, and molecular markers in bladder cancer (BC) demands sophisticated analytical methods. To identify novel biomarkers for predicting prognosis and immune function in BC patients, we combined weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression analysis. This was conducted using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Ultimately, we screened the junctional adhesion molecule 3 (JAM3) as an independent risk factor in BC. High levels of JAM3 were linked to adverse clinical parameters, such as higher T and N stages. Additionally, a JAM3-based nomogram model accurately predicted 1-, 3- and 5-year survival rates of BC patients, indicating potential clinical utility. Functional enrichment analysis revealed that high JAM3 expression activated the calcium signaling pathway, the extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway, and was positively correlated with genes associated with epithelial­mesenchymal transition (EMT). Subsequently, we found that overexpression of JAM3 promoted the migration and invasion abilities in BC cells, regulating the expression levels of N-Cadherin, matrix metallopeptidase 2 (MMP2), and Claudin-1 thereby promoting EMT levels. Additionally, we showed that JAM3 was negatively correlated with anti-tumor immune cells such as CD8+T cells, while positively correlated with pro-tumor immune cells such as M2 macrophages, suggesting its involvement in immune cell infiltration. The immune checkpoint CD200 also showed a positive correlation with JAM3. Our findings revealed that elevated JAM3 levels are predictive of poor prognosis and immune cell infiltration in BC patients by regulating the EMT process.