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BackgroundThis research seeks to formulate a prognostic model for forecasting prostate cancer recurrence by examining the interaction between mitochondrial function and programmed cell death (PCD).MethodsThe research involved analyzing four gene expression datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) using univariate Cox regression. These analyses identified genes linked with mitochondrial function and PCD that correlate with recurrence prognosis. Various machine learning algorithms were then employed to construct an optimal predictive model.ResultsA key outcome was the creation of a mitochondrial-related programmed cell death index (mtPCDI), which effectively predicts the prognosis of prostate cancer patients. It was observed that individuals with lower mtPCDI exhibited higher immune activity, correlating with better recurrence outcomes.ConclusionThe study demonstrates that mtPCDI can be used for personalized risk assessment and therapeutic decision-making, highlighting its clinical significance and providing insights into the biological processes affecting prostate cancer recurrence.

Lifestyle modification is an effective measure for diabetes prevention in people with prediabetes, but its associations with the long-term risks of cardiovascular disease (CVD), cancer, and mortality remain largely uncertain. We aimed to investigate the associations of combined healthy lifestyle factors with these health outcomes among participants with prediabetes. The study included 121 254 people with prediabetes from four prospective cohorts: the Dongfeng-Tongji (DFTJ) cohort and Kailuan study, both from China; the UK Biobank; and the US National Health and Nutrition Examination Survey (NHANES; for mortality analysis only). We documented a total of 18 333 incident diabetes, 10 829 incident CVD, 6926 incident cancer, and 9877 deaths during follow-up. Combined healthy lifestyle scores (scored from 0 to 5) were constructed based on never smoking or quitting smoking for ≥ 10 years, low-to-moderate alcohol drinking, optimal physical activity, healthy diet, and optimal waist circumference. First, Cox proportional-hazards regression models were used to quantify the associations of combined lifestyle score with health outcomes in each cohort; then, multivariable-adjusted hazard ratios (HRs) were pooled via a random-effects model of meta-analysis. Compared with participants with the least healthy lifestyle (a score of 0–1), participants with the healthiest lifestyle (a score of 4–5) had significantly reduced risks of all outcomes. The HRs (95% confidence interval (CI)) were 0.57 (0.48–0.69) for diabetes, 0.67 (0.62–0.73) for CVD, 0.80 (0.73–0.88) for cancer, and 0.54 (0.42–0.70) for mortality. Significant associations were consistently found across subgroups of baseline demographic characteristics and metabolic health status. In conclusion, our pooled analyses of four cohorts from three countries reveal that greater adherence to a healthy lifestyle is associated with considerably lower risks of diabetes and its major complications among adults with prediabetes. These findings provide informative and compelling evidence for establishing clinical guidelines and public health policies.

Background: Intratumoral hypoxia is widely associated with the development of malignancy, treatment resistance, and worse prognoses. The global influence of hypoxia-related genes (HRGs) on prognostic significance, tumor microenvironment characteristics, and therapeutic response is unclear in patients with non-small cell lung cancer (NSCLC).Method: RNA-seq and clinical data for NSCLC patients were derived from The Cancer Genome Atlas (TCGA) database, and a group of HRGs was obtained from the MSigDB. The differentially expressed HRGs were determined using the limma package; prognostic HRGs were identified via univariate Cox regression. Using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression, an optimized prognostic model consisting of nine HRGs was constructed. The prognostic model’s capacity was evaluated by Kaplan‒Meier survival curve analysis and receiver operating characteristic (ROC) curve analysis in the TCGA (training set) and GEO (validation set) cohorts. Moreover, a potential biological pathway and immune infiltration differences were explained.Results: A prognostic model containing nine HRGs (STC2, ALDOA, MIF, LDHA, EXT1, PGM2, ENO3, INHA, and RORA) was developed. NSCLC patients were separated into two risk categories according to the risk score generated by the hypoxia model. The model-based risk score had better predictive power than the clinicopathological method. Patients in the high-risk category had poor recurrence-free survival in the TCGA (HR: 1.426; 95% CI: 0.997–2.042; p = 0.046) and GEO (HR: 2.4; 95% CI: 1.7–3.2; p < 0.0001) cohorts. The overall survival of the high-risk category was also inferior to that of the low-risk category in the TCGA (HR: 1.8; 95% CI: 1.5–2.2; p < 0.0001) and GEO (HR: 1.8; 95% CI: 1.4–2.3; p < 0.0001) cohorts. Additionally, we discovered a notable distinction in the enrichment of immune-related pathways, immune cell abundance, and immune checkpoint gene expression between the two subcategories.Conclusion: The proposed 9-HRG signature is a promising indicator for predicting NSCLC patient prognosis and may be potentially applicable in checkpoint therapy efficiency prediction.

Abstract Background Ovarian cancer is the most lethal gynecological cancer which is characterized by extensive peritoneal implantation metastasis and malignant ascites. Despite advances in diagnosis and treatment in recent years, the five-year survival rate is only 25–30%. Therefore, developing multifunctional nanomedicine with abilities of promoting apoptosis and inhibiting migration on tumor cells would be a promising strategy to improve the antitumor effect. Methods and results In this study, we developed a novel ACaT nanomedicine composed of alendronate, calcium ions and cyclin-dependent kinase 7 (CDK7) inhibitor THZ1. With the average size of 164 nm and zeta potential of 12.4 mV, the spherical ACaT nanoparticles were selectively internalized by tumor cells and effectively accumulated in the tumor site. Results of RNA-sequencing and in vitro experiments showed that ACaT promoted tumor cell apoptosis and inhibited tumor cell migration by arresting the cell cycle, increasing ROS and affecting calcium homeostasis. Weekly intraperitoneally administered of ACaT for 8 cycles significantly inhibited the growth of tumor and prolonged the survival of intraperitoneal xenograft mice. Conclusion In summary, this study presents a new self-assembly nanomedicine with favorable tumor targeting, antitumor activity and good biocompatibility, providing a novel therapeutic strategy for advanced ovarian cancer. Graphical Abstract

The persistent heavy precipitation that occurred in most of West China (WC) during August 11–18, 2020, generated the highest rainfall record since recording began in 1961 and was selected as one of the top 10 worst national natural disasters of 2020 in China. Favorable circulation was sustained during August; WC was positioned between two anomalous high-pressure centers over the Tibetan Plateau and Sea of Japan and an anomalous low-pressure center over Mongolia located on its north side, which created a stable and long trough and formed a low-pressure center over WC. At 200 hPa, the subtropical westerly jet was much stronger than average and southward, and the South Asian High (SAH) was strong and extended eastward to 150°E. At 500 hPa, the western Pacific subtropical high (WPSH) was westward and exceptionally strong, which helped abundant water vapor reach the southeastern part of WC and provided favorable dynamic and thermodynamic conditions for precipitation in this region. In addition, the eastward extension of the SAH promotes the westward extension of WPSH, which collectively enhanced the precipitation in WC. At 850 hPa, the low-level jet corresponding to the west-extending subtropical high from the Sea of Japan to WC further enhanced and guided the water vapor transport to WC. In addition, the Mei-Yu front over the Yangtze River Basin in June and July strengthened the northwestward spread of diabatic heating, transient energy, and wave activity fluxes, which likely influenced the large-scale circulation factors and reinforced the precipitation in WC in August 2020.

Abstract Acute respiratory distress syndrome (ARDS) develops rapidly and has a high mortality rate. Survivors usually have low quality of life. Current clinical management strategies are respiratory support and restricted fluid input, and there is no suggested pharmacological treatment. Mesenchymal stromal cells (MSCs) have been reported to be promising treatments for lung diseases. MSCs have been shown to have a number of protective effects in some animal models of ARDS by releasing soluble, biologically active factors. In this review, we will focus on clinical progress in the use of MSCs as a cell therapy for ARDS, which may have clinical implications during the coronavirus disease 2019 (COVID-19) pandemic.

Abstract Background Colorectal carcinoma evolves through a multitude of molecular events including somatic mutations, epigenetic alterations, and aberrant protein expression, influenced by host immune reactions. One way to interrogate the complex carcinogenic process and interactions between aberrant events is to model a biomarker correlation network. Such a network analysis integrates multidimensional tumor biomarker data to identify key molecular events and pathways that are central to an underlying biological process. Due to embryological, physiological, and microbial differences, proximal and distal colorectal cancers have distinct sets of molecular pathological signatures. Given these differences, we hypothesized that a biomarker correlation network might vary by tumor location. Results We performed network analyses of 54 biomarkers, including major mutational events, microsatellite instability (MSI), epigenetic features, protein expression status, and immune reactions using data from 1380 colorectal cancer cases: 690 cases with proximal colon cancer and 690 cases with distal colorectal cancer matched by age and sex. Edges were defined by statistically significant correlations between biomarkers using Spearman correlation analyses. We found that the proximal colon cancer network formed a denser network (total number of edges, n = 173) than the distal colorectal cancer network (n = 95) (P

Large-scale genomic characterization of tumors from prospective cohort studies may yield new insights into cancer pathogenesis. We performed whole-exome sequencing of 619 incident colorectal cancers (CRCs) and integrated the results with tumor immunity, pathology, and survival data. We identified recurrently mutated genes in CRC, such as BCL9L, RBM10, CTCF, and KLF5, that were not previously appreciated in this disease. Furthermore, we investigated the genomic correlates of immune-cell infiltration and found that higher neoantigen load was positively associated with overall lymphocytic infiltration, tumor-infiltrating lymphocytes (TILs), memory T cells, and CRC-specific survival. The association with TILs was evident even within microsatellite-stable tumors. We also found positive selection of mutations in HLA genes and other components of the antigen-processing machinery in TIL-rich tumors. These results may inform immunotherapeutic approaches in CRC. More generally, this study demonstrates a framework for future integrative molecular epidemiology research in colorectal and other malignancies.

The environmental pollution generated by electronic waste (e-waste), waste-gas, and wastewater restricts the sustainable development of society. Environmental-friendly electronics made of degradable, resorbable, and compatible thin-film materials were utilized and explored, which was beneficial for e-waste dissolution and sustainable development. In this paper, we present a literature review about the development of various degradable and disposable thin-films for electronic applications. The corresponding preparation methods were simply reviewed and one of the most exciting and promising methods was discussed: Printing electronics technology. After a short introduction, detailed applications in the environment sensors and eco-friendly devices based on these degradable and compatible thin-films were mainly reviewed, finalizing with the main conclusions and promising perspectives. Furthermore, the future on these upcoming environmental-friendly electronic devices are proposed and prospected, especially on resistive switching devices, showing great potential applications in artificial intelligence (AI) and the Internet of Thing (IoT). These resistive switching devices combine the functions of storage and computations, which can complement the off-shelf computing based on the von Neumann architecture and advance the development of the AI.

Evidence suggests that activation of autophagy in neoplastic cells potentiates antitumor immunity through cross-presentation of tumor-associated antigens to T cells and release of immune mediators. The SQSTM1 (sequestosome 1, p62) protein is degraded by activated autophagy, and might enhance immune response to tumor cells. We hypothesized that tumor SQSTM1 expression level might be inversely associated with T-cell densities in colorectal carcinoma tissue. We evaluated tumor SQSTM1 expression by immunohistochemistry in 601 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study. Ordinal logistic regression analyses were conducted to assess the association of tumor SQSTM1 expression with CD3+, CD8+, CD45RO (PTPRC)+, or FOXP3+ cell density in tumor tissue, controlling for potential confounders, including tumor status of microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation level, and KRAS, BRAF, and PIK3CA mutations. Tumor SQSTM1 expression level was inversely associated with FOXP3+ cell density (ptrend = 0.006), but not with CD3+, CD8+, or CD45RO+ cell density (with the adjusted α level of 0.01 for multiple hypothesis testing). For a unit increase in quartile categories of FOXP3+ cell density, multivariable odds ratios were 0.66 [95% confidence interval (CI), 0.45–0.98] for intermediate-level SQSTM1 expression, and 0.55 (95% CI, 0.36–0.83) for high-level SQSTM1 expression, compared with low-level SQSTM1 expression. Tumor SQSTM1 expression is inversely associated with FOXP3+ cell density in colorectal cancer tissue, suggesting a possible role of SQSTM1-expressing carcinoma cells on regulatory T cells in the tumor microenvironment.

MicroRNAs (miRNAs) are a class of recently identified noncoding RNAs that regulate gene expression at posttranscriptional level. Due to the large number of genes regulated by miRNAs, miRNAs play important roles in many cellular processes. Emerging evidence indicates that miRNAs are dysregulated in pituitary adenomas, a class of intracranial neoplasms which account for 10–15% of diagnosed brain tumors. Deregulated miRNAs and their targets contribute to pituitary adenomas progression and are associated with cell cycle control, apoptosis, invasion, and pharmacological treatment of pituitary adenomas. To provide an overview of miRNAs dysregulation and functions of these miRNAs in pituitary adenoma progression, we summarize the deregulated miRNAs and their targets to shed more light on their potential as therapeutic targets and novel biomarkers.