Multi-omics characterization of macrophage polarization-related features in osteoarthritis based on a machine learning computational framework.

Background: OA imposes a heavy burden on patients and society in that its mechanism is still unclear, and there is a lack of effective targeted therapy other than surgery. Methods: The osteoarthritis dataset GSE55235 was downloaded from the GEO database and analyzed for differential genes by limma package, followed by analysis of immune-related modules by xcell immune infiltration combined with the WGCNA method, and macrophage polarization-related genes were downloaded according to the Genecard database, and VennDiagram was used to determine their intersection. These genes were also subjected to gene ontology (GO), disease ontology (DO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Using machine learning, the key osteoarthritis genes were finally screened. Using single gene GSEA and GSVA, we examined the significance of these key gene functions in immune cell and macrophage pathways. Next, we confirmed the correctness of the hub gene expression profile using the GSE55457 dataset and the ROC curve. Finally, we projected TF, miRNA, and possible therapeutic drugs using the miRNet, TargetScanHuman, ENCOR, and NetworkAnalyst databases, as well as Enrichr. Results: VennDiagram obtained 71 crossover genes for DEGs, WGCNA-immune modules, and Genecards; functional enrichment demonstrated NF-κB, IL-17 signaling pathway play an important role in osteoarthritis-macrophage polarization genes; machine learning finally identified CSF1R, CX3CR1, CEBPB, and TLR7 as hub genes; GSVA analysis showed that CSF1R, CEBPB play essential roles in immune infiltration and macrophage pathway; validation dataset GSE55457 analyzed hub genes were statistically different between osteoarthritis and healthy controls, and the AUC values of ROC for CSF1R, CX3CR1, CEBPB and TLR7 were more outstanding than 0.65. Conclusions: CSF1R, CEBPB, CX3CR1, and TLR7 are potential diagnostic biomarkers for osteoarthritis, and CSF1R and CEBPB play an important role in regulating macrophage polarization in osteoarthritis progression and are expected to be new drug targets.

Causal associations between dietary factors and colorectal cancer risk: a Mendelian randomization study.

Background: Previous epidemiological studies have found a link between colorectal cancer (CRC) and human dietary habits. However, the inherent limitations and inevitable confounding factors of the observational studies may lead to the inaccurate and doubtful results. The causality of dietary factors to CRC remains elusive. Methods: We conducted two-sample Mendelian randomization (MR) analyses utilizing the data sets from the IEU Open GWAS project. The exposure datasets included alcoholic drinks per week, processed meat intake, beef intake, poultry intake, oily fish intake, non-oily fish intake, lamb/mutton intake, pork intake, cheese intake, bread intake, tea intake, coffee intake, cooked vegetable intake, cereal intake, fresh fruit intake, salad/raw vegetable intake, and dried fruit intake. In our MR analyses, the inverse variance weighted (IVW) method was employed as the primary analytical approach. The weighted median, MR-Egger, weighted mode, and simple mode were also applied to quality control. Heterogeneity and pleiotropic analyses were implemented to replenish the accuracy of the results. Results: MR consequences revealed that alcoholic drinks per week [odds ratio (OR): 1.565, 95% confidence interval (CI): 1.068-2.293, p = 0.022], non-oily fish intake (OR: 0.286; 95% CI: 0.095-0.860; p = 0.026), fresh fruit intake (OR: 0.513; 95% CI: 0.273-0.964; p = 0.038), cereal intake (OR: 0.435; 95% CI: 0.253-0.476; p = 0.003) and dried fruit intake (OR: 0.522; 95% CI: 0.311-0.875; p = 0.014) was causally correlated with the risk of CRC. No other significant relationships were obtained. The sensitivity analyses proposed the absence of heterogeneity or pleiotropy, demonstrating the reliability of the MR results. Conclusion: This study indicated that alcoholic drinks were associated with an increased risk of CRC, while non-oily fish intake, fresh fruit intake, cereal intake, and dried fruit were associated with a decreased risk of CRC. This study also indicated that other dietary factors included in this research were not associated with CRC. The current study is the first to establish the link between comprehensive diet-related factors and CRC at the genetic level, offering novel clues for interpreting the genetic etiology of CRC and replenishing new perspectives for the clinical practice of gastrointestinal disease prevention.

Effects of exercise interventions on physical, psychological and social outcomes in frail older adults: An overview of systematic reviews.

AIMS: To comprehensively synthesise existing evidence from systematic reviews regarding the effects of exercise interventions on physical, psychological and social outcomes in frail older adults to provide reference for clinical practice. BACKGROUND: Frailty is highly prevalent in older adults and associated with increased adverse health outcomes. Some systematic reviews have assessed the effectiveness of exercise interventions in frail older adults with varied inclusion criteria, methodology quality, types of exercise and outcome measures. DESIGN: An overview of systematic reviews reported following the PRISMA checklist. METHODS: PubMed, Embase, CINAHL, Web of Science and Cochrane database were searched from inception until June 2023 to identify relevant systematic reviews with or without meta-analysis of randomised controlled trails. Two reviewers independently selected articles, extracted data, assessed quality and summarised findings. RESULTS: A total of 17 systematic reviews were included, with methodology quality varying from moderate to critically low. The most frequent types of exercise were multicomponent exercise and resistance-based exercise in community and long-term care facilities, respectively. Exercise interventions had positive effects on most physical outcomes and depression, but inconsistent effects on cognitive function and quality of life. The quality of the evidence for most outcomes was low and very low. CONCLUSIONS: This overview highlights the importance of exercise interventions to improve physical, psychological and social aspects in frail older adults and provides evidence on characteristics of exercise interventions for frailty in various settings. RELEVANCE TO CLINICAL PRACTICE: Multicomponent exercise and resistance-based exercise should be recommended for frail older adults. There is a need of more well-designed research with large sample size and validated definition of frailty. Long-term effects, adherence during and after exercise interventions, adverse events and cost-effectiveness should be emphasised in future studies. TRIAL AND PROTOCOL REGISTRATION: The overview protocol was registered on the International Prospective Register of Systematic reviews (CRD 42021281327). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REPORTING METHOD: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were applied to report the results.

Exosomal HMGB3 released by glioma cells confers the activation of NLRP3 inflammasome and pyroptosis in tumor-associated macrophages.

BACKGROUND: Previous evidences has highlighted the pivotal role of NOD-like receptor family pyrin domain-containing 3 (NLRP3)-mediated inflammasomes and pyroptosis activation in driving tumor malignancy and shaping the tumor microenvironment. Herein, we aimed to elucidate the impact of high-mobility group box 3 (HMGB3) released in glioma-derived exosomes on macrophage infiltration in gliomas, NLRP3 inflammasome activation and polarization. METHODS: Transcripts and protein levels of HMGB3, and cytokines associated with macrophage phenotypes and pyroptosis were assessed in glioma tissues and cell lines (U251, LN229, T98G, A172) using qRT-PCR and/or Western blot analysis. Exosomes secreted from LN229 and NHA cells were isolated via differential ultracentrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and analysis of exosome-related markers. PKH67 staining was employed to examine exosomes uptake by THP-1 differentiated macrophages. Flow cytometry was utilized to assess macrophage pyroptotic rates and polarization-related markers. RESULTS: HMGB3 expression was elevated in glioma tissues, serum samples and tumor cell lines. Kaplan-Meier curves revealed a positive correlation between higher HMGB3 expression and poor overall survival and recurrence-free survival. Moreover, glioma tissues with increased HMGB3 expression exhibited significant upregulation of M2 macrophages markers (CD68, CD206, Arg1) and NLRP3 inflammasome components (NLRP3, IL-1ß, ASC), suggesting that HMGB3 was closely associated with macrophage infiltration and NLRP3 inflammasome activation. Notably, HMGB3 was found to be enriched in glioma cell- secreted exosomes and could be internalized by macrophages. Knockdown of HMGB3 in glioma cell exosomes could restrain M2 macrophage polarization, NLRP3 inflammasome activation and pyroptosis. CONCLUSION: These findings suggested that glioma cells secreted exosomal HMGB3 could facilitate macrophage M2 polarization, pyroptosis and inflammatory infiltration, indicating HMGB3 might be a poor prognosis factor for glioma.

Comprehensive genetic analysis of facioscapulohumeral muscular dystrophy by Nanopore long-read whole-genome sequencing.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is a high-prevalence autosomal dominant neuromuscular disease characterized by significant clinical and genetic heterogeneity. Genetic diagnosis of FSHD remains a challenge because it cannot be detected by standard sequencing methods and requires a complex diagnosis workflow. METHODS: We developed a comprehensive genetic FSHD detection method based on Oxford Nanopore Technologies (ONT) whole-genome sequencing. Using a case-control design, we applied this procedure to 29 samples and compared the results with those from optical genome mapping (OGM), bisulfite sequencing (BSS), and whole-exome sequencing (WES). RESULTS: Using our ONT-based method, we identified 59 haplotypes (35 4qA and 24 4qB) among the 29 samples (including a mosaic sample), as well as the number of D4Z4 repeat units (RUs). The pathogenetic D4Z4 RU contraction identified by our ONT-based method showed 100% concordance with OGM results. The methylation levels of the most distal D4Z4 RU and the double homeobox 4 gene (DUX4) detected by ONT sequencing are highly consistent with the BSS results and showed excellent diagnostic efficiency. Additionally, our ONT-based method provided an independent methylation profile analysis of two permissive 4qA alleles, reflecting a more accurate scenario than traditional BSS. The ONT-based method detected 17 variations in three FSHD2-related genes from nine samples, showing 100% concordance with WES. CONCLUSIONS: Our ONT-based FSHD detection method is a comprehensive method for identifying pathogenetic D4Z4 RU contractions, methylation level alterations, allele-specific methylation of two 4qA haplotypes, and variations in FSHD2-related genes, which will all greatly improve genetic testing for FSHD.

All-solid-state ultrafast 2 µm laser with 1.83 W output power.

In this paper, a high-power all-solid-state ultrafast 2 µm mode-locked laser is investigated. The particularity of this laser is the simultaneous utilization of two Tm:YAP crystals in the same resonant cavity, independently pumped by two laser diodes. Using a 20% output coupler, pulses with output power as high as 1.83 W are achieved at a wavelength of 1938 nm with a pulse duration of 1.97 ps and a pulse repetition frequency of 100 MHz. To our knowledge, this mode-locked laser achieves the highest output power of any mode-locked Tm:YAP ultrafast laser reported to date. In addition, this paper provides a new approach to solve the problem of low output power due to multi-mode low-brightness laser diode pumping.

Mechanism Research of PZD Inhibiting Lung Cancer Cell Proliferation, Invasion, and Migration Based on Network Pharmacology.

BACKGROUND: A classic Chinese medicine decoction, Pinellia ternata (Thunb.) Breit-Zingiber officinale Roscoe (Ban-Xia and Sheng-Jiang in Chinese) decoction (PZD), has shown significant therapeutic effects on lung cancer. OBJECTIVE: This study aimed to explore and elucidate the mechanism of action of PZD on lung cancer using network pharmacology methods. METHODS: Active compounds were selected according to the ADME parameters recorded in the TCMSP database. Potential pathways related to genes were identified through GO and KEGG analysis. The compound target network was constructed by using Cytoscape 3.7.1 software, and the core common targets were obtained by protein-protein interaction (PPI) network analysis. Batch molecular docking of small molecule compounds and target proteins was carried out by using the AutoDock Vina program. Different concentrations of PZD water extracts (10, 20, 40, 80, and 160 µg/mL) were used on lung cancer cells. Moreover, MTT and Transwell experiments were conducted to validate the prominent therapeutic effects of PZD on lung cancer cell H1299. RESULTS: A total of 381 components in PZD were screened, of which 16 were selected as bioactive compounds. The compound-target network consisting of 16 compounds and 79 common core targets was constructed. MTT experiment showed that the PZD extract could inhibit the cell proliferation of NCI-H1299 cells, and the IC50 was calculated as 97.34 ± 6.14 µg/mL. Transwell and wound-healing experiments showed that the PZD could significantly decrease cell migration and invasion at concentrations of 80 and 160 µg/mL, respectively. The in vitro experiments confirmed that PZD had significant therapeutic effects on lung cancer cells, mainly through the PI3K/AKT signaling pathway. CONCLUSION: PZD could inhibit the cell proliferation, migration, and invasion of NCI-H1299 cells partially through the PI3K/AKT signaling pathway. These findings suggested that PZD might be a potential treatment strategy for lung cancer patients.

Does local soil factor drive functional leaf trait variation? A test on Neilingding Island, South China.

Leaf traits were affected by soil factors and displayed varietal differences in forest. However, few examples have been reported on the Island ecosystems. We comprehensively investigated 9 leaf traits (leaf length, leaf width, leaf area, SLA, leaf fresh weight, leaf C content, leaf N content, leaf K content, leaf C:N ratio) of 54 main subtropical woody species and soil parameters (soil pH, total C content, total N content, total K content, available N content, available P content, available K content and soil moisture) in Neilingding Island, Shenzhen, southern China. Intra-and interspecific variation of leaf traits were measured and their correlations with soil parameters were explored. The interspecific variations of leaf C:N ratio, leaf N content and leaf fresh weight were higher than their intraspecific variations. The intraspecific variation of leaf K content was larger than that of interspecific one, accounting for 80.69% of the total variance. Positive correlations were found among intraspecific coefficients of variations in leaf morphological traits. The correlation analysis between the variation of intraspecific traits and the variation of soil parameters showed that changes in soil factors affected leaf morphology and stoichiometry. The interaction between soil moisture and soil available P content was the key factor on intraspecific variations of leaf traits including leaf area, leaf fresh weight, leaf C and leaf K content. We concluded that leaf traits of plants in the island were tightly related to soil parameters. Soil parameters, especially soil moisture and available P content, affected plant leaf morphology and stoichiometry at the local scale.

Nanomedicine Remodels Tumor Microenvironment for Solid Tumor Immunotherapy.

Although immunotherapy is relatively effective in treating hematological malignancies, their efficacy against solid tumors is still suboptimal or even noneffective presently. Compared to hematological cancers, solid tumors exhibit strikingly different immunosuppressive microenvironment, severely deteriorating the efficacy of immunotherapy: (1) chemical features such as hypoxia and mild acidity suppress the activity of immune cells, (2) the pro-tumorigenic domestication of immune cells in the microenvironment within the solid tumors further undermines the effectiveness of immunotherapy, and (3) the dense physical barrier of solid tumor tissues prevents the effective intratumoral infiltration and contact killing of active immune cells. Therefore, we believe that reversing the immunosuppressive microenvironment are of critical priority for the immunotherapy against solid tumors. Due to their unique morphologies, structures, and compositions, nanomedicines have become powerful tools for achieving this goal. In this Perspective, we will first briefly introduce the immunosuppressive microenvironment of solid tumors and then summarize the most recent progresses in nanomedicine-based immunotherapy for solid tumors by remodeling tumor immune-microenvironment in a comprehensive manner. It is highly expected that this Perspective will aid in advancing immunotherapy against solid tumors, and we are highly optimistic on the future development in this burgeoning field.

RNAi efficiency is enhanced through knockdown of double-stranded RNA-degrading enzymes in butterfly Papilio xuthus.

The efficiency of RNA interference (RNAi) has always limited the research on the phenotype innovation of Lepidoptera insects. Previous studies have found that double-stranded RNA-degrading enzyme (dsRNase) is an important factor in RNAi efficiency, but there have been no relevant reports in butterflies (Papilionoidea). Papilio xuthus is one of the important models in butterflies with an extensive experimental application value. To explore the effect of dsRNase in the RNAi efficiency on butterflies, six dsRNase genes (PxdsRNase 1-6) were identified in P. xuthus genome, and their dsRNA-degrading activities were subsequently detected by ex vivo assays. The result shows that the dsRNA-degrading ability of gut content (<1 h) was higher than hemolymph content (>12 h). We then investigated the expression patterns of these PxdsRNase genes during different tissues and developmental stages, and related RNAi experiments were carried out. Our results show that different PxdsRNase genes had different expression levels at different developmental stages and tissues. The expression of PxdsRNase2, PxdsRNase3, and PxdsRNase6 were upregulated significantly through dsGFP injection, and PxdsRNase genes can be silenced effectively by injecting their corresponding dsRNA. RNAi-of-RNAi studies with PxEbony, which acts as a reporter gene, observed that silencing PxdsRNase genes can increase RNAi efficiency significantly. These results confirm that silencing dsRNase genes can improve RNAi efficiency in P. xuthus significantly, providing a reference for the functional study of insects such as butterflies with low RNAi efficiency.

LncRNA HMOX1 alleviates renal ischemia-reperfusion-induced ferroptotic injury via the miR-3587/HMOX1 axis.

Emerging evidence suggests that long non-coding RNAs (lncRNAs) play significant roles in renal ischemia reperfusion (RIR) injury. However, the specific mechanisms by which lncRNAs regulate ferroptosis in renal tubular epithelial cells remain largely unknown. The objective of this study was to investigate the biological function of lncRNA heme oxygenase 1 (lnc-HMOX1) in RIR and its potential molecular mechanism. Our findings demonstrated that the expression of HMOX1-related lnc-HMOX1 was reduced in renal tubular epithelial cells treated with hypoxia-reoxygenation (HR). Furthermore, the over-expression of lnc-HMOX1 mitigated ferroptotic injury in renal tubular epithelial cells in vivo and in vitro. Mechanistically, lnc-HMOX1, as a competitive endogenous RNA (ceRNA), promoted the expression of HMOX1 by sponging miR-3587. Furthermore, the inhibition of HMOX1 effectively impeded the aforementioned effects exerted by lnc-HMOX1. Ultimately, the inhibitory or mimic action of miR-3587 reversed the promoting or refraining influence of silenced or over-expressed lnc-HMOX1 on ferroptotic injury during HR. In summary, our findings contribute to a comprehensive comprehension of the mechanism underlying ferroptotic injury mediated by lnc-HMOX1 during RIR. Significantly, we identified a novel lnc-HMOX1-miR-3587-HMOX1 axis, which holds promise as a potential therapeutic target for RIR injury.

Targeted CQA analytical control strategy for commercial antibody products: Replacing ion-exchange chromatography methods for charge heterogeneity with multi-attribute monitoring.

Peptide mapping with mass spectrometry (MS) is an important tool for protein characterization in the biopharmaceutical industry. Historically, peptide mapping monitors post-translational modifications (PTMs) of protein products and process intermediates during development. Multi-attribute monitoring (MAM) methods have been used previously in commercial release and stability testing panels to ensure control of selected critical quality attributes (CQAs). Our goal is to use MAM methods as part of an overall analytical testing strategy specifically focused on CQAs, while removing or replacing historical separation methods that do not effectively distinguish CQAs from non-CQAs due to co-elution. For example, in this study, we developed a strategy to replace a profile-based ion-exchange chromatography (IEC) method using a MAM method in combination with traditional purity methods to ensure control of charge variant CQAs for a commercial antibody (mAb) drug product (DP). To support this change in commercial testing strategy, the charge variant CQAs were identified and characterized during development by high-resolution LC-MS and LC-MS/MS. The charge variant CQAs included PTMs, high molecular weight species, and low molecular weight species. Thus, removal of the IEC method from the DP specification was achieved using a validated LC-MS MAM method on a QDa system to directly measure the charge variant PTM CQAs in combination with size exclusion chromatography (SE-HPLC) and capillary electrophoresis (CE-SDS) to measure the non-PTM charge variant CQAs. Bridging data between the MAM, IEC, and SE-HPLC methods were included in the commercial marketing application to justify removing IEC from the DP specification. We have also used this MAM method as a test for identity to reduce the number of QC assays. This strategy has received approvals from several health authorities.

Microbiome signatures associated with clinical stages of gastric Cancer: whole metagenome shotgun sequencing study.

BACKGROUND: Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. RESULTS: A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. CONCLUSION: Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.

Reendothelialization of Acellular Adipose Flaps under Mimetic Physiological Dynamic Conditions.

The extensive soft-tissue defects resulting from trauma and tumors pose a prevalent challenge in clinical practice, characterized by a high incidence rate. Autologous tissue flap transplantation, considered the gold standard for treatment, is associated with various drawbacks, including the sacrifice of donor sources, postoperative complications, and limitations in surgical techniques, thereby impeding its widespread applicability. The emergence of tissue-engineered skin flaps, notably the acellular adipose flap (AAF), offers potential alternative solutions. However, a critical concern confronting large-scale tissue-engineered skin flaps currently revolves around the reendothelialization of internal vascular networks. In our study, we have developed an AAF utilizing perfusion decellularization, demonstrating excellent physical properties. Cytocompatibility experiments have confirmed its cellular safety, and cell adhesion experiments have revealed spatial specificity in facilitating endothelial cells adhesion within the adipose flap scaffold. Using a novel mimetic physiological fluid shear stress setting, endothelial cells were dynamically inoculated and cultured within the acellular vascular network of the pedicled AAF in our research. Histological and gene expression analyses have shown that the mimetic physiological fluid dynamic model significantly enhanced the reendothelialization of the AAF. This innovative platform of acellular adipose biomaterials combined with hydrodynamics may offer valuable insights for the design and manufacturing of 3D vascularized tissue constructs, which can be applied to the repair of extensive soft-tissue defects.

A PCR-independent approach for mtDNA enrichment and next-generation sequencing: comprehensive evaluation and clinical application.

BACKGROUND: Sequencing the mitochondrial genome has been increasingly important for the investigation of primary mitochondrial diseases (PMD) and mitochondrial genetics. To overcome the limitations originating from PCR-based mtDNA enrichment, we set out to develop and evaluate a PCR-independent approach in this study, named Pime-Seq (PCR-independent mtDNA enrichment and next generation Sequencing). RESULTS: By using the optimized mtDNA enrichment procedure, the mtDNA reads ratio reached 88.0 ± 7.9% in the sequencing library when applied on human PBMC samples. We found the variants called by Pime-Seq were highly consistent among technical repeats. To evaluate the accuracy and reliability of this method, we compared Pime-Seq with lrPCR based NGS by performing both methods simultaneously on 45 samples, yielding 1677 concordant variants, as well as 146 discordant variants with low-level heteroplasmic fraction, in which Pime-Seq showed higher reliability. Furthermore, we applied Pime-Seq on 4 samples of PMD patients retrospectively, and successfully detected all the pathogenic mtDNA variants. In addition, we performed a prospective study on 192 apparently healthy pregnant women during prenatal screening, in which Pime-Seq identified pathogenic mtDNA variants in 4 samples, providing extra information for better health monitoring in these cases. CONCLUSIONS: Pime-Seq can obtain highly enriched mtDNA in a PCR-independent manner for high quality and reliable mtDNA deep-sequencing, which provides us an effective and promising tool for detecting mtDNA variants for both clinical and research purposes.

Psychological Traditionality and Modernity and Happiness: The Different Happiness Levels in Chinese Students.

The conceptualization of happiness varies across different cultures. In Chinese culture, happiness includes oneself and hinges on others. Chinese social development has influenced psychological traditionality (PT), psychological modernity (PM), and personal happiness. Our study recruited 450 participants to examine the different happiness levels in Chinese students with diverse PT and PM. The results indicate that individuals scoring higher in PT and PM reported higher life satisfaction. Moreover, individuals scoring higher in PT reported more positive emotions, fewer negative emotions, and greater social well-being, while those scoring higher in PM reported more negative emotions and greater relationship happiness. The happiness of Chinese students comprised individual, relational, and societal levels and happiness at different levels related to Chinese PT and PM. The present study may promote cross-cultural understanding and potentially inform interventions for individual happiness within positive psychology.

Microvesicles from Mesenchymal Stem Cells Overexpressing MiR-34a Ameliorate Renal Fibrosis In Vivo.

INTRODUCTION: We recently discovered that microvesicles (MVs)  derived from mesenchymal stem cells (MSCs) overexpressing  miRNA-34a can alleviate experimental kidney injury in mice. In  this study, we further explored the effects of miR34a-MV on renal  fibrosis in the unilateral ureteral obstruction (UUO) models.  Methods. Bone marrow MSCs were modified by lentiviruses  overexpressing miR-34a, and MVs were collected from the  supernatants of MSCs. C57BL6/J mice were divided into control,  unilateral ureteral obstruction (UUO), UUO + MV, UUO + miR-34aMV and UUO + miR-34a-inhibitor-MV groups. MVs were injected  to mice after surgery. The mice were then euthanized on day 7  and 14 of modeling, and renal tissues were collected for further  analyses by Hematoxylin and eosin, Masson's trichrome,  and Immunohistochemical (IHC) staining.  Results. The UUO + MV group exhibited a significantly reduced  degree of renal interstitial fibrosis with inflammatory cell infiltration,  tubular epithelial cell atrophy, and vacuole degeneration compared  with the UUO group. Surprisingly, overexpressing miR-34a enhanced  these effects of MSC-MV on the UUO mice.  Conclusion. Our study demonstrates that miR34a further enhances  the effects of MSC-MV on renal fibrosis in mice through the  regulation of epithelial-to-mesenchymal transition (EMT) and  Notch pathway. miR-34a may be a candidate molecular therapeutic  target for the treatment of renal fibrosis. DOI: 10.52547/ijkd.7673.

Use of circulating tumor cells and microemboli to predict diagnosis and prognosis in diffuse glioma.

OBJECTIVE: Circulating tumor cell (CTC) detection is a promising noninvasive technique that can be used to diagnose cancer, monitor progression, and predict prognosis. In this study, the authors aimed to investigate the clinical utility of CTCs in the management of diffuse glioma. METHODS: Sixty-three patients with newly diagnosed diffuse glioma were included in this multicenter clinical cohort. The authors used a platform based on isolation by size of epithelial tumor cells (ISET) to detect and analyze CTCs and circulating tumor microemboli (CTMs) in the peripheral blood of patients both before and after surgery. Least absolute shrinkage and selector operation (LASSO) and Cox regression analyses were used to verify whether CTCs and CTMs are independent prognostic factors for diffuse glioma. RESULTS: CTC levels were closely related to the degree of malignancy, WHO grade, and pathological subtypes. Receiver operating characteristic curve analysis revealed that a high CTC level was a predictor for glioblastoma. The results also showed that CTMs originate from the parental tumor rather than from the circulation and are an independent prognostic factor for diffuse glioma. The postoperative CTC level is related to the peripheral immune system and patient survival. Cox regression analysis showed that postoperative CTC levels and CTM status are independent prognostic factors for diffuse glioma, and CTC- and CTM-based survival models had high accuracy in internal validation. CONCLUSIONS: The authors revealed a correlation between CTCs and clinical characteristics and demonstrated that CTCs and CTMs are independent predictors for the diagnosis and prognosis of diffuse glioma. Their CTC- and CTM-based survival models can enable clinicians to evaluate patients' response to surgery as well as their outcomes.

Effects of the immune system on muscle regeneration.

Muscle regeneration is a complex process orchestrated by multiple steps. Recent findings indicate that inflammatory responses could play central roles in bridging initial muscle injury responses and timely muscle injury reparation. The various types of immune cells and cytokines have crucial roles in muscle regeneration process. In this review, we provide an overview of the functions of acute inflammation in muscle regeneration.

TGF-ß1-triggered BMI1 and SMAD2 cooperatively regulate miR-191 to modulate bone formation.

Transforming growth factor ß 1 (TGF-ß1), as the most abundant signaling molecule in bone matrix, is essential for bone homeostasis. However, the signaling transduction of TGF-ß1 in the bone-forming microenvironment remains unknown. Here, we showed that microRNA-191 (miR-191) was downregulated during osteogenesis and further decreased by osteo-favoring TGF-ß1 in bone marrow mesenchymal stem cells (BMSCs). MiR-191 was lower in bone tissues from children than in those from middle-aged individuals and it was negatively correlated with collagen type I alpha 1 chain (COL1A1). MiR-191 depletion significantly increased osteogenesis and bone formation in vivo. Hydrogels embedded with miR-191-low BMSCs displayed a powerful bone repair effect. Mechanistically, transcription factors BMI1 and SMAD2 coordinately controlled miR-191 level. In detail, BMI1 and pSMAD2 were both upregulated by TGF-ß1 under osteogenic condition. SMAD2 activated miR-191 transcription, while BMI1 competed with SMAD2 for binding to miR-191 promoter region, thus disturbing the activation of SMAD2 on miR-191 and reducing miR-191 level. Altogether, our findings reveal that miR-191 regulated by TGF-ß1-induced BMI1 and SMAD2 negatively modulated bone formation and regeneration, and inhibition of miR-191 might be therapeutically useful to enhance bone repair in clinic.