DNA methylation clocks for estimating biological age in Chinese cohorts.

Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation at specific CpG sites. However, available DNA methylation (DNAm) age predictors are based on datasets with limited ethnic representation. Moreover, a systematic comparison between DNAm data and other omics datasets has not yet been performed. To address these knowledge gaps, we generated and analyzed DNA methylation datasets from two independent Chinese cohorts, revealing age-related DNAm changes. Additionally, a DNA methylation (DNAm) aging clock (iCAS-DNAmAge) and a group of DNAm-based multi-modal clocks for Chinese individuals were developed, with most of them demonstrating strong predictive capabilities for chronological age. The clocks were further employed to predict factors influencing aging rates. The DNAm aging clock, derived from multi-modal aging features (compositeAge-DNAmAge), exhibited a close association with multi-omics changes, lifestyles, and disease status, underscoring its robust potential for precise biological age assessment. Our findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace, providing basis for evaluating aging intervention strategies.

A pyroptosis gene-based prognostic model for predicting survival in low-grade glioma.

Background: Pyroptosis, a lytic form of programmed cell death initiated by inflammasomes, has been reported to be closely associated with tumor proliferation, invasion and metastasis. However, the roles of pyroptosis genes (PGs) in low-grade glioma (LGG) remain unclear. Methods: We obtained information for 1,681 samples, including the mRNA expression profiles of LGGs and normal brain tissues and the relevant corresponding clinical information from two public datasets, TCGA and GTEx, and identified 45 differentially expressed pyroptosis genes (DEPGs). Among these DEPGs, nine hub pyroptosis genes (HPGs) were identified and used to construct a genetic risk scoring model. A total of 476 patients, selected as the training group, were divided into low-risk and high-risk groups according to the risk score. The area under the curve (AUC) values of the receiver operating characteristic (ROC) curves verified the accuracy of the model, and a nomogram combining the risk score and clinicopathological characteristics was used to predict the overall survival (OS) of LGG patients. In addition, a cohort from the Gene Expression Omnibus (GEO) database was selected as a validation group to verify the stability of the model. qRT-PCR was used to analyze the gene expression levels of nine HPGs in paracancerous and tumor tissues from 10 LGG patients. Results: Survival analysis showed that, compared with patients in the low-risk group, patients in the high-risk group had a poorer prognosis. A risk score model combining PG expression levels with clinical features was considered an independent risk factor. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that immune-related genes were enriched among the DEPGs and that immune activity was increased in the high-risk group. Conclusion: In summary, we successfully constructed a model to predict the prognosis of LGG patients, which will help to promote individualized treatment and provide potential new targets for immunotherapy.

TRIM28 recruits E2F1 to regulate CBX8-mediated cell proliferation and tumor metastasis of ovarian cancer.

Chromobox protein homolog 8 (CBX8) is a transcriptional suppressor participated in various cancers. However, the function and mechanism of CBX8 in the progression of ovarian cancer (OC) are unclear. In this study, we found that CBX8 was upregulated in OC tissues originating from GEPIA and TNM databases, OC patients' samples from hospital, and OC cell lines. Furthermore, CBX8 knockdown by short hairpin RNA (shRNA) technology markedly inhibited proliferation and invasion, induced migration, cell cycle arrest, and apoptosis in vitro. Mechanistically, CBX8 activated PI3K/AKT/mTOR signaling pathway to take effect. In addition, TRIM28 and E2F1 were enriched in OC tissues from the TNM database and OC patients' samples similar to the results of CBX8. Correlation analysis indicated positive correlations among TRIM28, E2F1, and CBX8. E2F1 was proved to bind to the promoter regions of CBX8 and TRIM28, while TRIM28 recruited E2F1 to increase the expression of CBX8 to further increase cell viability, proliferation, and invasion, and decrease migration, apoptosis, and cell cycle progression. Finally, CBX8 or TRIM28 knockdown repressed tumor growth and metastasis of OC in vivo. Therefore, our study showed that the promoting effect of CBX8 on tumor growth and metastasis of OC was participated in the PI3K/AKT/mTOR signaling, TRIM28 and E2F1. Our findings suggested that CBX8 could serve as a potential marker and therapeutic target for OC patients.

Determining a multimodal aging clock in a cohort of Chinese women.

BACKGROUND: Translating aging rejuvenation strategies into clinical practice has the potential to address the unmet needs of the global aging population. However, to successfully do so requires precise quantification of aging and its reversal in a way that encompasses the complexity and variation of aging. METHODS: Here, in a cohort of 113 healthy women, tiled in age from young to old, we identified a repertoire of known and previously unknown markers associated with age based on multimodal measurements, including transcripts, proteins, metabolites, microbes, and clinical laboratory values, based on which an integrative aging clock and a suite of customized aging clocks were developed. FINDINGS: A unified analysis of aging-associated traits defined four aging modalities with distinct biological functions (chronic inflammation, lipid metabolism, hormone regulation, and tissue fitness), and depicted waves of changes in distinct biological pathways peak around the third and fifth decades of life. We also demonstrated that the developed aging clocks could measure biological age and assess partial aging deceleration by hormone replacement therapy, a prevalent treatment designed to correct hormonal imbalances. CONCLUSIONS: We established aging metrics that capture systemic physiological dysregulation, a valuable framework for monitoring the aging process and informing clinical development of aging rejuvenation strategies. FUNDING: This work was supported by the National Natural Science Foundation of China (32121001), the National Key Research and Development Program of China (2022YFA1103700 and 2020YFA0804000), the National Natural Science Foundation of China (81502304), and the Quzhou Technology Projects (2022K46).

Jin-Zhen oral liquid for pediatric coronavirus disease (COVID-19): A randomly controlled, open-label, and non-inferiority trial at multiple clinical centers.

Background: As the coronavirus disease 2019 (COVID-19) pandemic progressed, especially with the emergence of the Omicron variant, the proportion of infected children and adolescents increased significantly. Some treatment such as Chinese herbal medicine has been administered for COVID-19 as a therapeutic option. Jin-Zhen Oral Liquid is widely used for pediatric acute bronchitis, while the efficacy and safety in the treatment of pediatric COVID-19 are unclear. Methods: We conducted a randomized controlled, open-label, multicenter, non-inferiority clinical study involving hospitalized children with mild to moderate COVID-19. Children eligible for enrollment were randomly assigned in a 1:1 ratio to Jin-Zhen Oral Liquid (the treatment group) and Jinhua Qinggan Granules (the positive control group) and received the respective agent for 14 days, followed by a 14-day follow-up after discontinuation of the treatment. The primary efficacy endpoint was the time to first negative viral testing. The secondary endpoints were the time and rate of major symptoms disappearance, duration of hospitalization, and the proportion of symptoms changed from asymptomatic or mild to moderate or severe/critical illness. In addition, the safety end points of any adverse events were observed. Results: A total of 240 child patients were assigned randomly into the Jin-Zhen Oral Liquid (117 patients) and Jinhua Qinggan Granules (123 patients) groups. There was no significant difference of the baselines in terms of the clinical characteristics and initial symptoms between the two groups. After 14-day administration, the time to first negative viral testing in the Jin-Zhen group (median 6.0 days, 95% CI 5.0-6.0) was significantly shorter compared with the positive control Jinhua Qinggan Granules group (median 7.0 days, 95% CI 7.0-8.0). The time and rate of major clinical symptoms disappearance were comparable to the positive control. The symptom disappearance time of pharyngalgia and hospitalization duration were significantly shortened in the Jin-zhen Oral Liquid group. No participants in either group experienced post-treatment exacerbation to severe or critical illness. No adverse events were observed in the Jin-Zhen Oral Liquid treatment group (0.0%) while 1 patient with adverse events occurred in the positive control Jinhua Qinggan granules group (0.8%). No serious adverse events were observed during the study period in both groups. Conclusion: Jin-Zhen Oral Liquid is safe and effective in the treatment of mild to medium COVID-19 in children. It is non-inferior to Jinhua Qinggan granules in shortening the time to first negative viral testing, the time and rate of major clinical symptoms disappearance, and the hospitalization duration. The results suggest that Jin-Zhen Oral Liquid can be a recommended drug for treatment of pediatric COVID-19 patients.

Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging.

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.

Analysis of the effect of phototherapy on intestinal probiotics and metabolism in newborns with jaundice.

Background: In clinical practice, oral probiotics are often given to children with hyperbilirubinaemia who receive phototherapy, but the exact mechanism of the action of the probiotics on hyperbilirubinaemia remains unclear. It is unclear how the effects of phototherapy on the probiotic flora in the neonatal gut, in particular. Materials and methods: Fifty newborns who needed phototherapy from June 2018 to June 2020 were selected as the study subjects, and five healthy newborns in the same period were used as controls to analyse the changes in probiotic bacteria in their faeces. Results: 1. In the intestinal tracts of newborns, Bifidobacterium is the main probiotic strain, with a small amount of Lactobacillus. There were probiotic species changes in the neonatal intestinal microbiota after phototherapy for 24 and 48 h. The amount of Bifidobacterium and Lactobacillus decreased significantly (P < 0.05). 2. A correlation analysis of probiotic species and bile acid metabolism indexes showed that Bifidobacterium was positively correlated with many metabolites (P < 0.05), such as chenodeoxycholic acid, hyodeoxycholic acid, cholic acid, allocholic acid, and ß-cholic acid. It was also negatively correlated with many metabolites (P < 0.05), such as glycocholic acid, sodium, sodium tudca, and chenodeoxycholic acid. Lactobacillus was negatively correlated with metabolites (P < 0.05) such as α-sodium cholate and ß-cholic acid. 3. A correlation analysis between the changes in probiotics and intestinal short-chain fatty acid metabolites after phototherapy showed that acetic acid, butyric acid, caproic acid, and propionic acid decreased and were significantly correlated with Bifidobacterium (P < 0.05). 4. After phototherapy, 17 metabolites changed significantly (P < 0.05). This correlated with many probiotics (P < 0.05). The significantly changed probiotics in this study showed a significant correlation with some intestinal metabolites (P < 0.05). Conclusion: It was found that phototherapy can significantly affect the intestinal probiotic flora and the metabolic indicators of newborns, which may be an important reason for the side effects of phototherapy, and also provides the theoretical basis for the provision of probiotics to newborns with jaundice.

Optimization of whole-cell vaccines with CpG/αOX40/cGAMP to strengthen the anti-tumor response of CD4+ T cells in melanomas.

METHODS: In this study, we developed a strategy for the prevention and therapy of melanoma using a whole-cell vaccine combined with a CpG/αOX40/cGAMP triple adjuvant. The CpG/αOX40/cGAMP triple adjuvant was used to co-culture melanoma cells in vitro to induce immunogenic death of tumor cells. The mixture of inactivated tumor cells and the triple drug was an optimized tumor whole-cell vaccine, which was injected subcutaneously into mice for tumor prevention and therapy. Furthermore, we analyzed the changes of immune cells in spleen and tumor by flow cytometry and immunohistochemistry, and detected the changes of cytokines after vaccine application by cytometric bead array to explore the specific mechanism of vaccine. RESULTS: In vaccine prevention and therapy experiments, it was observed that the tumor growth was significantly inhibited in the whole-cell vaccine group, and the survival time of mice was significantly prolonged. Flow cytometry results showed that the proportion of CD4+ T cells and CD8+ T cells in tumor of mice in vaccine group was higher than that in control group, especially the CD4+ T cells. CONCLUSION: The optimized vaccine has the unique ability to amplify tumor-specific CD4+ T cells, which improves antitumor sensitivity, and has a significant effect on the prevention and therapy of melanoma mice.

High-Throughput and Untargeted Metabolic Profiling Revealed the Potential Effect and Mechanisms of Paeoniflorin in Young Asthmatic Rats.

Paeoniflorin (PF) is a multi-target monoterpenoid glycoside and possesses broad pharmacological functions, e.g., anti-inflammation, anti-depression, antitumor, abirritation, neuroprotection, antioxidant, and enhancing cognitive and learning ability. PF has gained a large amount of attention for its effect on asthma disease as the growth rate of asthma has increased in recent years. However, its mechanism of action on asthma is still unclear. In this study, we have explored the action mechanism of PF on asthma disease. Furthermore, high-throughput untargeted metabolic profiling was performed through ultraperformance liquid chromatography/electrospray ionization quadruple time-of-flight high-definition mass spectrometry (QA) UPLC-Q/TOF-MS combined with pattern recognition approaches and pathway analysis. A total of 20 potential biomarkers were discovered by UPLC/MS and urine metabolic profiling. The key pathways including the citrate cycle (the TCA cycle), pyrimidine metabolism, pentose phosphate pathway, tyrosine metabolism, and tryptophan metabolism were affected by PF. In conclusion, we have discovered metabolite biomarkers and revealed the therapeutic mechanism of PF based on liquid chromatography coupled with mass spectrometry untargeted metabolomics. The untargeted metabolomics combined with UPLC-MS is a useful tool for exploring the therapeutic mechanism and targets of PF in the treatment of asthma. Metabolomics combined with UPLC-MS is an integrated method to explore the metabolic mechanism of PF in the treatment of asthma rats and to reveal the potential targets, providing theoretical support for the study of the treatment of PF.

Construction and Verification of a Combined Hypoxia and Immune Index for Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most aggressive malignancies in humans. Hypoxia-related genes are now recognized as a reflection of poor prognosis in cancer patients with cancer. Meanwhile, immune-related genes play an important role in the occurrence and progression of ccRCC. Nevertheless, reliable prognostic indicators based on hypoxia and immune status have not been well established in ccRCC. The aims of this study were to develop a new gene signature model using bioinformatics and open databases and to validate its prognostic value in ccRCC. The data used for the model structure can be accessed from The Cancer Genome Atlas database. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were used to identify the hypoxia- and immune-related genes associated with prognostic risk, which were used to develop a characteristic model of prognostic risk. Kaplan-Meier and receiver-operating characteristic curve analyses were performed as well as independent prognostic factor analyses and correlation analyses of clinical characteristics in both the training and validation cohorts. In addition, differences in tumor immune cell infiltrates were compared between the high and low risk groups. Overall, 30 hypoxia- and immune-related genes were identified, and five hypoxia- and immune-related genes (EPO, PLAUR, TEK, TGFA, TGFB1) were ultimately selected. Survival analysis showed that the high-risk score on the hypoxia- and immune-related gene signature was significantly associated with adverse survival outcomes. Furthermore, clinical ccRCC samples from our medical center were used to validate the differential expression of the five genes in tumor tissue compared to normal tissue through quantitative real-time polymerase chain reaction (qRT-PCR). However, more clinical trials are needed to confirm these results, and future experimental studies must verify the potential mechanism behind the predictive value of the hypoxia- and immune-related gene signature.

Circular RNA mmu_circ_0001295 from hypoxia pretreated adipose-derived mesenchymal stem cells (ADSCs) exosomes improves outcomes and inhibits sepsis-induced renal injury in a mouse model of sepsis.

Microvascular dysfunction causes mortality in the presence of sepsis and multi-organ failure. Previous studies have demonstrated that exogenous administration of exosomes from adipose-derived mesenchymal stem cells (ADSCs) protects against sepsis, improves organ function, decreases vascular leakage and increases survival. However, the underlying regulatory mechanism was largely unknown. Therefore, in this study, a mouse sepsis model based on cecal ligation and puncture (CLP) was constructed. Exosomes from various ADSCs were intravenously administered at 4 h post CLP. Treatment with ADSC exosomes (Exo), particularly those with hypoxic pretreatment (HExo), enhanced survival, suppressed renal vascular leakage and decreased kidney dysfunction in septic mice. HExo ameliorated sepsis-induced increases in chemokine and cytokine plasma levels. Furthermore, the HExo circRNA content, determined through next-generation sequencing, revealed abundant mmu_circ_0001295. Further studies demonstrated that downregulation of exosomal mmu_circ_0001295 suppressed the exosomes' protective effects against sepsis. HExo prevented microvascular dysfunction, thus potentially improving sepsis outcomes via mmu_circ_0001295 delivery. In summary, the data indicated that HExo elongate sepsis-induced renal injury through delivering mmu_circ_0001295.

Robust immune response stimulated by in situ injection of CpG/αOX40/cGAMP in αPD-1-resistant malignancy.

Recently, the emergence of immunotherapy has revolutionized traditional tumour treatment. However, effective treatments for patients exhibiting αPD-1 resistance are still lacking. In our study, a combination of cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODNs), anti-OX40 and cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) injection in situ systematically generated a robust antitumour immune response in TC1 and B16 cells, which are αPD-1-resistant malignancies. More precisely, this method activates both adaptive and innate immunity. Additionally, in situ vaccination with CpG/αOX40/cGAMP fully activates the production of cytokines. However, the combination of αPD-1 does not improve the efficacy of triple therapy, prompting further questions. Collectively, the combination of CpG/αOX40/cGAMP causes the regression of various αPD-1-resistant tumours through the full mobilization of innate and adaptive immunity. In addition, we explored the therapeutic effect of triple therapy on the αPD-1-sensitive cell line CT26. The results showed that triple therapy could significantly enhance the therapeutic effect of αPD-1, and some mice even achieved complete tumour regression after the combined application of αPD-1 and triple treatment.

Construction and validation of a novel aging-related gene signature and prognostic nomogram for predicting the overall survival in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is the most lethal gynecological malignancy. The objective of this study was to establish and validate an individual aging-related gene signature and a clinical nomogram that can powerfully predict independently the overall survival rate of patients with ovarian cancer. METHODS: Data on transcriptomic profile and relevant clinical information were retrieved from The Cancer Genome Atlas (TCGA) database as a training group, and the same data from three public Gene Expression Omnibus (GEO) databases as validation groups. Univariate Cox regression analysis, lasso regression analysis, and multiple multivariate Cox analysis were analyzed sequentially to select the genes to be included in the aging-associated signature. A risk scoring model was established and verified, the predictive value of the model was evaluated, and a clinical nomogram was established. RESULTS: We found eight genes that were most relevant to prognosis and constructed an eight-mRNA signature. Based on the model, each OC patient's risk score was able to be calculated and patients were split into groups of low and high risks with a distinct outcome. Survival analysis confirmed that the outcome of patients in the high-risk group was dramatically shorter than that of those in the low-risk group, and the eight-mRNA signature can be considered as a powerful and independent predictor that could predict the outcome of OC patient. Additionally, the risk score and age can be used to construct a clinical nomogram as a simpler tool for predicting prognosis. We also explored the association between the risk score and immunity and drug sensitivity. CONCLUSION: This study suggested that the aging-related gene signature could be used as an intervention point and latent prognostic predictor in OC, which may provide new perceptions for postoperative treatment strategies.

Development of an Interferon Gamma Response-Related Signature for Prediction of Survival in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Interferon plays a crucial role in the pathogenesis and progression of tumors. Clear cell renal cell carcinoma (ccRCC) represents a prevalent malignant urinary system tumor. An effective predictive model is required to evaluate the prognosis of patients to optimize treatment. MATERIALS AND METHODS: RNA-sequencing data and clinicopathological data from TCGA were involved in this retrospective study. The IFN-γ response genes with significantly different gene expression were screened out. Univariate Cox regression, LASSO regression and multivariate Cox regression were used to establish a new prognostic scoring model for the training group. Survival curves and ROC curves were drawn, and nomogram was constructed. At the same time, we conducted subgroup analysis and experimental verification using our own samples. Finally, we evaluated the relatedness between the prognostic signature and immune infiltration landscapes. In addition, the sensitivity of different risk groups to six drugs and immune checkpoint inhibitors was calculated. RESULTS: The IFN-γ response-related signature included 7 genes: C1S, IFI44, ST3GAL5, NUP93, TDRD7, DDX60, and ST8SIA4. The survival curves of the training and testing groups showed the model's effectiveness (P = 4.372e-11 and P = 1.08e-08, respectively), the ROC curves showed that the signature was stable, and subgroup analyses showed the wide applicability of the model (P<0.001). Multivariate Cox regression analysis showed that the risk model was an independent prognostic factor of ccRCC. A high-risk score may represent an immunosuppressive microenvironment, while the high-risk group exhibited poor sensitivity to drugs. CONCLUSION: Our findings strongly indicate that the IFN-γ response-related signature can be used as an effective prognostic indicator of ccRCC.

Anti-tumour effect of in situ vaccines combined with VEGFR inhibitors in the treatment of metastatic cervical cancer.

Cervical cancer is the fourth most common malignant tumor in the world, for advanced cervical cancer, more than 30% of patients continue to have tumor and relapse or metastasis after the traditional treatment (concurrent chemoradiotherapy), and the response rate of immune checkpoint inhibitor (PD-1) is less 15%, so additional approaches are required. In situ vaccine is a very promising immunotherapy strategy. In the preclinical study, the combination of CPG and anti-Ox40 antibody can completely resolve injection site tumours and distant tumours and leads to the recovery of most mice with lymphoma. However, our early exploration process found that the effect of CpG + OX40 in the treatment of advanced cervical cancer is not ideal. Hence, we explored the anti-tumor effect of CpG + OX40 combined with anti-angiogenic therapy for the first time. The results showed that the combination significantly inhibited the proliferation of primary and secondary tumor volume and prolonged the survival time of mice, compared with the control group, CD3+, CD4 + and CD8 + T cells in the combined group showed an increasing trend. In addition, in terms of metabolism, the anti-vascular effect of anlotinib can significantly reduce the blood supply and metabolic level of tumor, the expression of Ki67 and CD31 in the control group was significantly higher than that in each administration group. In conclusion, our preclinical research results showed that the combination of in situ vaccine and anti-angiogenic therapy has a good anti-tumor effect, and may potentially offer an effective treatment option for patients with advanced cervical cancer.

Construction and Verification of a Hypoxia-Related 4-lncRNA Model for Prediction of Breast Cancer.

INTRODUCTION: Breast cancer is the most common form of cancer worldwide and a serious threat to women. Hypoxia is thought to be associated with poor prognosis of patients with cancer. Long non-coding RNAs are differentially expressed during tumorigenesis and can serve as unambiguous molecular biomarkers for the prognosis of breast cancer. METHODS: Here, we accessed the data from The Cancer Genome Atlas for model construction and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to identify biological functions. Four prognostic hypoxia-related lncRNAs identified by univariate, LASSO, and multivariate Cox regression analyses were used to develop a prognostic risk-related signature. Kaplan-Meier and receiver operating characteristic curve analyses were performed, and independent prognostic factor analysis and correlation analysis with clinical characteristics were utilized to evaluate the specificity and sensitivity of the signature. Survival analysis and receiver operating characteristic curve analyses of the validation cohort were operated to corroborate the robustness of the model. RESULTS: Our results demonstrate the development of a reliable prognostic gene signature comprising four long non-coding RNAs (AL031316.1, AC004585.1, LINC01235, and ACTA2-AS1). The signature displayed irreplaceable prognostic power for overall survival in patients with breast cancer in both the training and validation cohorts. Furthermore, immune cell infiltration analysis revealed that B cells, CD4 T cells, CD8 T cells, neutrophils, and dendritic cells were significantly different between the high-risk and low-risk groups. The high-risk and low-risk groups could be precisely distinguished using the risk signature to predict patient outcomes. DISCUSSION: In summary, our study proves that hypoxia-related long non-coding RNAs serve as accurate indicators of poor prognosis and short overall survival, and are likely to act as potential targets for future cancer therapy.

Combined analysis of microbial community and microbial metabolites based on untargeted metabolomics during pig manure composting.

Compost has been widely used in agriculture in recent years, but the nutrients it provides are far from enough for plant growth. Therefore, it is necessary to systematically explore the fermentation process of composting. In this study, the succession of microbial community and metabolite characteristics in compost were analyzed by using microbial sequencing and metabolomics techniques. The results showed that compared with mesophilic phase and cooling phase, the richness and diversity of bacterial community decreased in thermophilic phase. At the genus level, Pseudomonas (8.90%), Lactobacillus (3.99%), Bacteroidetes (3.39%), Flavobacterium (3.25%) and Prevotella (Prevotella_9, 2.33%, Prevotellaceae_NK3B31_group, 2.44%) were the dominant genera in the pig manure composting. The abundance of Pseudomonas and Flavobacterium increased significantly while Lactobacillus and Prevotella were significantly decreased after composting, and the abundance of Bacteroidetes increased first and then decreased. Fatty acyls, sterol lipids, glycerophospholipids, polyketides and prenol lipids were common microbial metabolites in compost. Moreover, the linoleic acid metabolic pathway was significantly enriched in the three stages of composting, and linoleic acid metabolism might be the primary function of the microbial community in composting. The network analysis showed that between the microbial communities or between the microbial community and metabolites were closely related to each other.

Biocompatibility nanoprobe of MXene N-Ti3C2 quantum dot/Fe3+ for detection and fluorescence imaging of glutathione in living cells.

MXene quantum dots have attracted much attention due to their great optical performance and excellent water solubility. Glutathione (GSH) plays a key role in living cells. In this study, a biocompatibility nanoprobe was prepared for detecting intracellular GSH based on MXene N-Ti3C2 quantum dots (N-Ti3C2 QDs). The N-Ti3C2 QDs act as the fluorescence reporters and the ferric iron (Fe3+) as the quenchers based on nonradiative electron-hole annihilation. When Fe3+ encounters the amino group of N-Ti3C2 QDs, the electrons of N-Ti3C2 QDs in the excited state will transfer to the half-filled 3d orbitals of Fe3+, leading to the fluorescence quenching of N-Ti3C2 QDs. When the N-Ti3C2 QDs/Fe3+ nanoprobe acts on the cancer cell MCF-7, the abundant GSH in the cancer cells can reduce Fe3+ to Fe2+, which will restore the fluorescence of N-Ti3C2 QDs. The N-Ti3C2 QDs/Fe3+ nanoprobe displays a high sensitivity for GSH with a detection limit of 0.17 µM in range of 0.5-100 µM. It becomes a promising probe for detecting and showing cellular imaging of GSH in MCF-7 cells. The N-Ti3C2 QDs/Fe3+ nanoprobe might provide a new way for imaging-guided precision cancer diagnosis.

Ultrasensitive detection of cyclin D1 by a self-enhanced ECL immunosensor based on Bi2S3 quantum dots.

Bismuth sulfide quantum dots (Bi2S3 QDs), which have excellent optical and thermoelectric properties, represent a green and non-toxic semiconductor material that has been widely used in catalysis and photoelectric conversion devices. At present, research on this material has gradually expanded into the biological field. Herein, the biomineralization method mediated by bovine serum albumin (BSA) was utilized to synthesize Bi2S3 QDs with monodispersity, excellent colloidal stability, and good biocompatibility. This is the first study on the electrochemiluminescence (ECL) characteristics of Bi2S3 QDs and related ECL mechanisms in detail. In addition, on the basis of Bi2S3 QDs, an ECL immunosensor was used for the ultrasensitive measurement of cyclin D1 (CCND1). The composite material, namely Au@Cu-Bi2S3 QDs was used as a high-sensitivity ECL probe, in which AuNPs were connected with Bi2S3 QDs through a copper(ii) ion bridge. PDA-AgNPs made of dopamine (DA) and silver nanoparticles (AgNPs) were utilized as a carrier for fixing the primary antibody (Ab1), ultimately presenting a relatively wide detection range of 10 fg mL-1-1 µg mL-1. Moreover, quite a low detection limit (6.34 fg mL-1) was also obtained for an assay of CCND1. Results indicated that the immunosensor can provide a potential platform with fine stability and creditable reproducibility for clinical diagnosis.

Identification of EMT-Related Gene Signatures to Predict the Prognosis of Patients With Endometrial Cancer.

BACKGROUND: Endometrial cancer (EC) is one of the most common gynecological cancers. Epithelial-mesenchymal transition (EMT) is believed to be significantly associated with the malignant progression of tumors. However, there is no relevant study on the relationship between EMT-related gene (ERG) signatures and the prognosis of EC patients. METHODS: We extracted the mRNA expression profiles of 543 tumor and 23 normal tissues from The Cancer Genome Atlas database. Then, we selected differentially expressed ERGs (DEERGs) among these mRNAs. Next, univariate and multivariate Cox regression analyses were performed to select the ERGs with predictive ability for the prognosis of EC patients. In addition, risk score models were constructed based on the selected genes to predict patients' overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Finally, nomograms were constructed to estimate the OS and PFS of EC patients, and pan-cancer analysis was performed to further analyze the functions of a certain gene. RESULTS: Six OS-, ten PFS-, and five DFS-related ERGs were obtained. By constructing the prognostic risk score model, we found that the OS, PFS, and DFS of the high-risk group were notably poorer. Last, we found that AQP5 appeared in all three gene signatures, and through pan-cancer analysis, it was also found to play an important role in immunity in lower grade glioma (LGG), which may contribute to the poor prognosis of LGG patients. CONCLUSIONS: We constructed ERG signatures to predict the prognosis of EC patients using bioinformatics methods. Our findings provide a thorough understanding of the effect of EMT in patients with EC and provide new targets and ideas for individualized treatment, which has important clinical significance.