Dietary calcium is inversely associated with hepatitis B virus infection: an analysis of US National Health and Nutrition Examination Survey (NHANES) 2007-2020.

BACKGROUND: There have been studies on the relationship between hepatitis B virus (HBV) infection and diet. We hypothesized HBV infection is related to dietary calcium intake, but the evidence is limited. This study aimed to examine whether dietary calcium intake is independently related to HBV infection in the United States population. METHODS: A total of 20,488 participants aged over 20 years from the National Health and Nutrition Examination Survey (NHANES), conducted from 2007 to 2020, were included in this study. Pearson correlation was used to test the association between dietary calcium and serum calcium. The relationships of HBV infection with dietary calcium and serum calcium were assessed by logistic regression models. RESULTS: There was a weak correlation between dietary calcium and serum calcium (r = 0.048). Logistic regression models indicated that HBV infection had a linear negative correlation with dietary calcium (OR 0.37; 95%CI 0.19, 0.76). For each additional 10 mg dietary calcium, the possibility of HBV infection was reduced by 63%. Hepatitis B positive participants had lower serum calcium content than negative participants. Stratified analysis shown the linear relationship between calcium and HBV infection varied among sex, race/ethnicity, and body mass index. CONCLUSION: Our findings demonstrated HBV infection was linearly and inversely correlated with dietary calcium. The current study is expected to offer a fresh perspective on reducing HBV infection.

ncRNADrug: a database for validated and predicted ncRNAs associated with drug resistance and targeted by drugs.

Drug resistance is a major barrier in cancer treatment and anticancer drug development. Growing evidence indicates that non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play pivotal roles in cancer progression, therapy, and drug resistance. Furthermore, ncRNAs have been proven to be promising novel therapeutic targets for cancer treatment. Reversing dysregulated ncRNAs by drugs holds significant potential as an effective therapeutic strategy for overcoming drug resistance. Therefore, we developed ncRNADrug, an integrated and comprehensive resource that records manually curated and computationally predicted ncRNAs associated with drug resistance, ncRNAs targeted by drugs, as well as potential drug combinations for the treatment of resistant cancer. Currently, ncRNADrug collects 29 551 experimentally validated entries involving 9195 ncRNAs (2248 miRNAs, 4145 lncRNAs and 2802 circRNAs) associated with the drug resistance of 266 drugs, and 32 969 entries involving 10 480 ncRNAs (4338 miRNAs, 6087 lncRNAs and 55 circRNAs) targeted by 965 drugs. In addition, ncRNADrug also contains associations between ncRNAs and drugs predicted from ncRNA expression profiles by differential expression analysis. Altogether, ncRNADrug surpasses the existing related databases in both data volume and functionality. It will be a useful resource for drug development and cancer treatment. ncRNADrug is available at http://www.jianglab.cn/ncRNADrug.

Decreasing expression of Prohibitin-2 lowers the oncogenicity of renal cell carcinoma cells by suppressing eIF4E-mediated oncogene translation via MNK inhibition.

Prohibitin-2 (PHB2) serves as a key signalling protein that is connected with diverse cellular functions. PHB2 overexpression frequently occurs in cancers and is closely related to tumorigenesis. So far, the connection between PHB2 and renal cell carcinoma (RCC) has not been discussed yet. The purpose of this study was to explore the expression and biological function of PHB2 in RCC and to uncover the underlying mechanisms. High level of PHB2 was found in RCC tissues, and this overexpression was linked to a worse overall survival rate for RCC patients. In RCC cell, the lowering of PHB2 generated tumour-inhibiting effects in RCC cells such as proliferation retardation, cell cycle arrest, suppression of the capacity for metastasis, and chemosensitivity enhancement. Mechanistically, PHB2 mediated the activation of eukaryotic initiation factor 4E (eIF4E) and the translation of oncogenic proteins via the regulation of MNK. The inhibition of MNK diminished the effects of PHB2 on eIF4E-medited oncogene translation. The overexpression of eIF4E reversed PHB2-reduction-evoked tumour-inhibiting effects. Moreover, RCC cells with decreasing PHB2 exhibited a weakened ability to form xenografts in vivo. In conclusion, these findings show that PHB2 is pivotal for RCC progression and suggest that inhibiting MNK/eIF4E by decreasing PHB2 is a potential pathway for the treatment of RCC.

DRdriver: identifying drug resistance driver genes using individual-specific gene regulatory network.

Drug resistance is one of principal limiting factors for cancer treatment. Several mechanisms, especially mutation, have been validated to implicate in drug resistance. In addition, drug resistance is heterogeneous, which makes an urgent need to explore the personalized driver genes of drug resistance. Here, we proposed an approach DRdriver to identify drug resistance driver genes in individual-specific network of resistant patients. First, we identified the differential mutations for each resistant patient. Next, the individual-specific network, which included the genes with differential mutations and their targets, was constructed. Then, the genetic algorithm was utilized to identify the drug resistance driver genes, which regulated the most differentially expressed genes and the least non-differentially expressed genes. In total, we identified 1202 drug resistance driver genes for 8 cancer types and 10 drugs. We also demonstrated that the identified driver genes were mutated more frequently than other genes and tended to be associated with the development of cancer and drug resistance. Based on the mutational signatures of all driver genes and enriched pathways of driver genes in brain lower grade glioma treated by temozolomide, the drug resistance subtypes were identified. Additionally, the subtypes showed great diversity in epithelial-mesenchyme transition, DNA damage repair and tumor mutation burden. In summary, this study developed a method DRdriver for identifying personalized drug resistance driver genes, which provides a framework for unlocking the molecular mechanism and heterogeneity of drug resistance.

LncRNA HCP5-Encoded Protein Regulates Ferroptosis to Promote the Progression of Triple-Negative Breast Cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) are a class of RNA molecules that are longer than 200 nucleotides and were initially believed to lack encoding capability. However, recent research has found open reading frames (ORFs) within lncRNAs, suggesting that they may have coding capacity. Despite this discovery, the mechanisms by which lncRNA-encoded products are involved in cancer are not well understood. The current study aims to investigate whether lncRNA HCP5-encoded products promote triple-negative breast cancer (TNBC) by regulating ferroptosis. METHODS: We used bioinformatics to predict the coding capacity of lncRNA HCP5 and conducted molecular biology experiments and a xenograft assay in nude mice to investigate the mechanism of its encoded products. We also evaluated the expression of the HCP5-encoded products in a breast cancer tissue microarray. RESULTS: Our analysis revealed that the ORF in lncRNA HCP5 can encode a protein with 132-amino acid (aa), which we named HCP5-132aa. Further experiments showed that HCP5-132aa promotes TNBC growth by regulating GPX4 expression and lipid ROS level through the ferroptosis pathway. Additionally, we found that the breast cancer patients with high levels of HCP5-132aa have poorer prognosis. CONCLUSIONS: Our study suggests that overexpression of lncRNA HCP5-encoded protein is a critical oncogenic event in TNBC, as it regulates ferroptosis. These findings could provide new therapeutic targets for the treatment of TNBC.

scDR: Predicting Drug Response at Single-Cell Resolution.

Heterogeneity exists inter- and intratumorally, which might lead to different drug responses. Therefore, it is extremely important to clarify the drug response at single-cell resolution. Here, we propose a precise single-cell drug response (scDR) prediction method for single-cell RNA sequencing (scRNA-seq) data. We calculated a drug-response score (DRS) for each cell by integrating drug-response genes (DRGs) and gene expression in scRNA-seq data. Then, scDR was validated through internal and external transcriptomics data from bulk RNA-seq and scRNA-seq of cell lines or patient tissues. In addition, scDR could be used to predict prognoses for BLCA, PAAD, and STAD tumor samples. Next, comparison with the existing method using 53,502 cells from 198 cancer cell lines showed the higher accuracy of scDR. Finally, we identified an intrinsic resistant cell subgroup in melanoma, and explored the possible mechanisms, such as cell cycle activation, by applying scDR to time series scRNA-seq data of dabrafenib treatment. Altogether, scDR was a credible method for drug response prediction at single-cell resolution, and helpful in drug resistant mechanism exploration.

Long-Term Survival and Prognostic Factors After Laparoscopic Radical Nephrectomy.

Purpose: Our study aims to investigate the long-term survival and prognostic factors of patients after laparoscopic radical nephrectomy. Methods: Totally, 245 patients with renal cell carcinoma in our hospital from January 2015 to February 2017 were analyzed retrospectively. The 5-year survival status of patients with renal cell carcinoma was under analysis and further based on univariate analysis, and its influencing factors were analyzed by Cox regression. Results: The average 5-year follow-up time of 245 patients with renal cell carcinoma was (4.88 ± 0.52) years. The mortality of 1 year, 3 years and 5 years were 2.45% (5/245), 6.35% (16/245) and 9.80% (24/245), respectively. The survival rates were 97.55% (239/245), 93.06% (228/245) and 90.61% (222/245). Univariate analysis showed that age, tumor diameter, hematuria, TNM stage and postoperative recurrence may be the influencing factors of 5-year survival of patients with renal cell carcinoma (P < .05). However, the following parameters, including gender, course of disease, and other clinical complications were not related to the 5-year survival of patients with renal cell carcinoma (P > .05). the influencing factors of 5-year survival status of patients with renal cell carcinoma were age, tumor diameter, hematuria, TNM stage, and postoperative recurrence. Conclusion: The study revealed the long-term survival of patients with renal cell carcinoma may be associated with age, tumor diameter, hematuria, TNM stage and postoperative recurrence.

ncFO: A Comprehensive Resource of Curated and Predicted ncRNAs Associated with Ferroptosis.

Ferroptosis is a form of regulated cell death driven by the accumulation of lipid hydroperoxides. Regulation of ferroptosis might be beneficial to cancer treatment. Non-coding RNAs (ncRNAs) are a class of RNA transcripts that generally cannot encode proteins and have been demonstrated to play critical roles in regulating ferroptosis. Herein, we developed ncFO, the ncRNA-ferroptosis association database, to document the manually curated and predicted ncRNAs that are associated with ferroptosis. Collectively, ncFO contains 90 experimentally verified entries, including 46 microRNAs (miRNAs), 21 long non-coding RNAs (lncRNAs), and 17 circular RNAs (circRNAs). In addition, ncFO also incorporates two online prediction tools based on the regulation and co-expression of ncRNA and ferroptosis genes. Using default parameters, we obtained 3260 predicted entries, including 598 miRNAs and 178 lncRNAs, by regulation, as well as 2,592,661 predicted entries, including 967 miRNAs and 9632 lncRNAs, by ncRNA-ferroptosis gene co-expression in more than 8000 samples across 20 cancer types. The detailed information of each entry includes ncRNA name, disease, species, tissue, target, regulation, publication time, and PubMed identifier. ncFO also provides survival analysis and differential expression analysis for ncRNAs. In summary, ncFO offers a user-friendly platform to search and predict ferroptosis-associated ncRNAs, which might facilitate research on ferroptosis and discover potential targets for cancer treatment. ncFO can be accessed at http://www.jianglab.cn/ncFO/.

Estimating Metastatic Risk of Pancreatic Ductal Adenocarcinoma at Single-Cell Resolution.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by intra-tumoral heterogeneity, and patients are always diagnosed after metastasis. Thus, finding out how to effectively estimate metastatic risk underlying PDAC is necessary. In this study, we proposed scMetR to evaluate the metastatic risk of tumor cells based on single-cell RNA sequencing (scRNA-seq) data. First, we identified diverse cell types, including tumor cells and other cell types. Next, we grouped tumor cells into three sub-populations according to scMetR score, including metastasis-featuring tumor cells (MFTC), transitional metastatic tumor cells (TransMTC), and conventional tumor cells (ConvTC). We identified metastatic signature genes (MSGs) through comparing MFTC and ConvTC. Functional enrichment analysis showed that up-regulated MSGs were enriched in multiple metastasis-associated pathways. We also found that patients with high expression of up-regulated MSGs had worse prognosis. Spatial mapping of MFTC showed that they are preferentially located in the cancer and duct epithelium region, which was enriched with the ductal cells' associated inflammation. Further, we inferred cell-cell interactions, and observed that interactions of the ADGRE5 signaling pathway, which is associated with metastasis, were increased in MFTC compared to other tumor sub-populations. Finally, we predicted 12 candidate drugs that had the potential to reverse expression of MSGs. Taken together, we have proposed scMetR to estimate metastatic risk in PDAC patients at single-cell resolution which might facilitate the dissection of tumor heterogeneity.

[Sleep patterns of infants and young children and their association with breastfeeding: a study based on K-means clustering]. / 基于K-meansèšç±»åˆ†æžçš„å©´å¹¼å„¿ç¡çœ æ¨¡å¼åŠä¸Žæ¯ä¹³å–‚å »å ³ç³»çš„ç ”ç©¶.

OBJECTIVES: To investigate the sleep patterns and characteristics of infants and young children and the association between sleep patterns and breastfeeding. METHODS: A general information questionnaire, Brief Infant Sleep Questionnaire (BISQ), and a questionnaire on feeding were used to investigate the sleep quality and feeding patterns of 1 148 infants and young children aged 7-35 months. The K-means clustering method was used to identify sleep patterns and characteristics. A multivariate logistic regression analysis was used to investigate the association between sleep patterns and breastfeeding. RESULTS: Three typical sleep patterns were identified for the 1 148 infants and young children aged 7-35 months: early bedtime and long sleep time; short sleep latency and moderate sleep time; late bedtime, prolonged sleep latency, and insufficient sleep time. The third pattern showed sleep disorders. The multivariate logistic regression analysis showed that compared with formula feeding, exclusive breastfeeding within 6 months after birth reduced the risk of sleep disorder patterns by 69% (OR=0.31, 95%CI: 0.11-0.81). The risk of sleep disorder patterns was reduced by 40% (OR=0.60, 95%CI: 0.38-0.96) in the infants receiving breastfeeding for 4-6 months compared with those receiving breastfeeding for 1-3 months. CONCLUSIONS: There are different sleep patterns in infants and young children, and breastfeeding can reduce the development of sleep disorder patterns.

CTpathway: a CrossTalk-based pathway enrichment analysis method for cancer research.

BACKGROUND: Pathway enrichment analysis (PEA) is a common method for exploring functions of hundreds of genes and identifying disease-risk pathways. Moreover, different pathways exert their functions through crosstalk. However, existing PEA methods do not sufficiently integrate essential pathway features, including pathway crosstalk, molecular interactions, and network topologies, resulting in many risk pathways that remain uninvestigated. METHODS: To overcome these limitations, we develop a new crosstalk-based PEA method, CTpathway, based on a global pathway crosstalk map (GPCM) with >440,000 edges by combing pathways from eight resources, transcription factor-gene regulations, and large-scale protein-protein interactions. Integrating gene differential expression and crosstalk effects in GPCM, we assign a risk score to genes in the GPCM and identify risk pathways enriched with the risk genes. RESULTS: Analysis of >8300 expression profiles covering ten cancer tissues and blood samples indicates that CTpathway outperforms the current state-of-the-art methods in identifying risk pathways with higher accuracy, reproducibility, and speed. CTpathway recapitulates known risk pathways and exclusively identifies several previously unreported critical pathways for individual cancer types. CTpathway also outperforms other methods in identifying risk pathways across all cancer stages, including early-stage cancer with a small number of differentially expressed genes. Moreover, the robust design of CTpathway enables researchers to analyze both bulk and single-cell RNA-seq profiles to predict both cancer tissue and cell type-specific risk pathways with higher accuracy. CONCLUSIONS: Collectively, CTpathway is a fast, accurate, and stable pathway enrichment analysis method for cancer research that can be used to identify cancer risk pathways. The CTpathway interactive web server can be accessed here http://www.jianglab.cn/CTpathway/ . The stand-alone program can be accessed here https://github.com/Bioccjw/CTpathway .

DNA methylation dynamics associated with long-term isolation of simulated space travel.

Long-term isolation is one of the risk factors that astronauts will encounter in spaceflight. At present, few researches have explored DNA methylation dynamics during long-term isolation. In this study, using time series DNA methylation data from "Mars-500" mission, we conducted a multi-step analysis to investigate the characteristics and dynamic patterns of DNA methylation as well as their functional insights during long-term isolation. The results showed that genome-wide methylation changes were minimal. In the six identified DNA methylation dynamic patterns, most of significantly fluctuating CpG sites could be returned to the baseline in post-isolation, and the remaining sites persistently decreased during isolation. Next, functional enrichment analysis of genes with each pattern revealed strong functional specificity. Some patterns were also significantly associated with nervous system diseases, digestive system diseases and cancers. In conclusion, the DNA methylation dynamics during long-term isolation have great functional significance, and might be helpful for protection of astronaut health.

[Intervention effects of erythropoietin derived peptide (HBSP) on renal injury induced by acute skeletal muscle strain in rats].

Objective: To investigate the protective effects of erythropoietin derived peptide, also known as spiral B surface peptide (HBSP), on kidney and aggregated proteins (Agrin) levels in acute skeletal muscle strain rats. Methods: Forty SPF grade SD male rats were randomly divided into control group, injury group, HBSP group and EPO group, with 10 rats in each group. Acute skeletal muscle strain animal models were established except the control group. After successful modeling, the rats in HBSP group and EPO group were intraperitoneally injected with 60 µg/kg HBSP and 5 000 U/kg recombinant human erythropoietin (rhEPO), and the rats in the control group and the injured group were intraperitoneally injected with 0.9% normal saline. Renal function was monitored with relevant kits; Hematoxylin-eosin staining was used to observe the pathological morphology of kidney tissue and skeletal muscle strain tissue. The apoptosis rate of renal tissue cells was detected by in situ terminal transferase labeling (TUNEL). Western blot and quantitative polymerase chain reaction (Q-PCR) were used to determine the expressions of Agrin and muscular-specific kinase (MuSK) in the injured skeletal muscle of rats in each group. Results: Compared with the control group, the renal function indexes serum creatinine (Cr), urea nitrogen (BUN) and 24 h urinary protein (UP24) levels of rats in injured group were increased (P＜ 0.05), but the levels of BUN, Cr and UP24 of rats in HBSP group were decreased (P＜0.05). Compared with HBSP group, there were no significant differences in the above indexes in EPO group (P＞0.05). In the control group, the muscle fiber structure was intact, the shape and structure of the fiber bundles were normal, and there was no infiltration of red blood cells and inflammatory cells in the interstitium, and no fibrohyperplasia. In the injured group, the muscle tissue showed sparse and irregular arrangement, and the interstitial widened with a large number of inflammatory cells and red blood cell infiltration. Erythrocytes and inflammatory cells were reduced in HBSP group and EPO group, and the transverse and longitudinal lines of muscle were clear. The glomerular structure of the rats in the fibrohyperplasia control group was intact and no lesions were observed. In the injured group, glomerular hypertrophy and significant matrix hyperplasia were observed, as well as the expansion of renal cysts with vacuolar and significant inflammatory infiltration were observed, and the inflammatory infiltration was reduced in the HBSP and EPO groups. Glomerular hypertrophy and hyperplasia were alleviated. The apoptosis rates of kidney cells in control group, injured group, HBSP group and EPO group were (4.05±0.51) %, (26.30±2.05) %, (14.28±1.62) % and (16.03±1.77) %, respectively, and there were significant differences among these groups (P＜0.05). Compared with control group, the levels of Agrin and MuSK in skeletal muscle pulled tissue were significantly decreased (P＜0.05), and those of HBSP group and EPO group were significantly increased compared with injured group (P＜0.05), but there was no significant difference between HBSP group and EPO group (P＞0.05). Conclusion: Erythropoietin derived peptide (HBSP) has obvious intervention effects on renal function injury in rats with acute skeletal muscle strain, and its mechanisms may be related to reducing the apoptosis rate of renal tissue cells and activating Agrin and MuSK expression.

[Individualized whole-course management in prostatic puncture biopsy: Application and efficiency].

OBJECTIVE: To evaluate the application of individualized whole-course management (IWCM) in prostatic puncture biopsy. METHODS: We reviewed the clinical data on 280 cases of ultrasound-guided transrectal prostatic puncture biopsy performed in our department from June 2016 to October 2017. We assigned the patients to an observation group (P = 140) and a control group (P = 140), the former given IWCM － preoperative education, intraoperative nursing care and postoperative guidance for complication prevention, while the latter going through only the routine procedures of preoperative talk and assigning of operation agreement. We compared the incidence of postoperative complications, blood pressure change and heart rate fluctuation of the patients and their satisfaction with IWCM. RESULTS: Prostatic puncture operations were successfully completed in all the patients. Compared with the controls, the patients in the observation group showed a significantly lower incidence rate of postoperative complications (P < 0.05), less significant fluctuation in blood pressure and heart rate intra- and postoperatively (P < 0.05), lower intraoperative pain scores (P < 0.05), and higher satisfaction with IWCM (80% ［112/140］ vs 95.7% ［134/140］, P < 0.05). CONCLUSION: Preoperative education, intraoperative nursing care and postoperative guidance for complication prevention can reduce the incidence of postoperative complications and improve the satisfaction of the patients undergoing ultrasound-guided prostate puncture.

[Efficacy of biofeedback and electrical stimulation therapy combined with Sabale capsules for chronic prostatitis / chronic pelvic pain syndrome].

Objective: To investigate the clinical effect of biofeedback and electrical stimulation therapy (BFES) combined with Sabale capsules (SC) on chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS). METHODS: A total of 140 outpatients meeting CP/CPPS diagnostic and research criteria in the Second Affiliated Hospital of Xi'an Jiaotong University were randomly divided into groups A (blank control), B (BFES intervention), C (SC intervention) and D (BFES+SC intervention), 35 cases in each group. The patients in group A were left untreated, while those in groups B, C and D received BFES, SC and BFES+SC, respectively, all for 12 weeks. Then the patients were followed up at 30 days after treatment and the urinary flow rate and NIH-CPSI scores were obtained and compared with the baseline. RESULTS: In comparison with the baseline, the total NIH-CPSI scores after intervention were significantly decreased in groups B, (ï¼»27.30 ± 2.44ï¼½ vs ï¼»19.43 ± 2.33ï¼½), C (ï¼»26.77 ± 2.54ï¼½ vs ï¼»19.40 ± 2.75ï¼½) and D (ï¼»27.67 ± 3.69ï¼½ vs ï¼»15.57 ± 1.94ï¼½) (all P < 0.05), and so were the individual item scores in pain or discomfort (ï¼»12.50 ± 1.94ï¼½ vs ï¼»9.40 ± 2.01ï¼½, ï¼»11.93 ± 1.64ï¼½ vs ï¼»9.23 ± 1.96ï¼½, and ï¼»12.33 ± 2.20ï¼½ vs ï¼»7.50 ± 1.55ï¼½), urination symptoms (ï¼»6.07 ± 1.57ï¼½ vs ï¼»3.83 ± 1.05ï¼½, ï¼»5.97 ± 1.33ï¼½ vs ï¼»3.77 ± 1.14ï¼½, and ï¼»6.20 ± 1.88ï¼½ vs ï¼»2.87 ± 0.94ï¼½), quality of life (QOL) (ï¼»8.73 ± 1.62ï¼½ vs ï¼»6.20 ± 1.42ï¼½, ï¼»8.87 ± 1.25ï¼½ vs ï¼»6.40 ± 1.59ï¼½, and ï¼»9.13 ± 1.70ï¼½ vs ï¼»5.20 ± 1.40ï¼½) (all P < 0.05), while the maximum urinary flow rate (Qmax) was remarkably increased (ï¼»15.72 ± 2.38ï¼½ vs ï¼»19.73 ± 2.85ï¼½, ï¼»16.20 ± 2.44ï¼½ vs ï¼»19.46 ± 2.48ï¼½, and ï¼»15.83 ± 2.52ï¼½ vs ï¼»22.49 ± 2.76ï¼½) (all P < 0.05), and so was the average urinary flow rate (Qavg) (ï¼»9. 282 ± 1.52ï¼½ vs ï¼»11.27 ± 1.95ï¼½, ï¼»8.97 ± 1.25ï¼½ vs ï¼»11.16 ± 1.74ï¼½, and ï¼»9.20 ± 1.36ï¼½ vs ï¼»13.50 ± 2.30ï¼½) (all P < 0.05). The decrease in NIH-CPSI total and item scores and increase in Qmax and Qavg after treatment were more significant in group D than in B and C (P < 0.05), but showed no statistically significant difference between groups B and C (P > 0.05). Nor was any significant change observed in the above parameters in group A after treatment ( P > 0.05). CONCLUSIONS: Biofeedback and electrical stimulation therapy combined with Sabale capsules can alleviate urination dysfunction, pelvic floor tension myalgia and other symptoms and significantly improve the QOL of CP/CPPS patients.

Multi-Dopant Engineering in Perovskite Cs2SnCl6: White Light Emitter and Spatially Luminescent Heterostructure.

Bi3+/Te4+ co-doped Cs2SnCl6 with dual emission spectrum (i.e., 450 and 575 nm) was achieved by a modified solution method, which can overcome the phase separation in the previous method for Cs2SnCl6 crystal growth. The two emission peaks arising from the two dopants Bi3+ and Te4+ have distinct photoluminescence (PL) lifetimes. Thus, the control of dopant ratio or PL delay time will regulate the PL intensity ratio between 450 and 575 nm peaks leading to adjustable emission color. The energy transfer between the two emission centers, which is confirmed by the optical spectra and PL lifetime, has a critical distance around 7.8 nm with a maximum of 50% transfer efficiency. The Bi3+/Te4+ co-doped Cs2SnCl6 with superior stability in water and aqua regia was fabricated into a single-phase white light-emitting diode. In the meantime, various luminescent heterostructures were obtained by epitaxial Cs2SnCl6 crystal growth with different dopants, which can broaden the study of composition engineering in halide perovskites.

Se4P4nanoparticles confined within porous carbon as a lithium-ion battery anode with superior electrochemical performance.

The exploration of advanced anode materials through rational structure/phase design is the key to developing high-performance rechargeable batteries. Herein, tetraphosphorus tetraselenide (Se4P4) nanoparticles confined within porous carbon (named SeP@C) are developed for lithium-ion batteries. The designed SeP@C shows a set of structural/compositional advantages as lithium-ion battery anodes including high electrical conductivity, low ion diffusion barrier, and relieved lithiation stress. Consequently, the SeP@C electrode displays superior comprehensive lithium storage performance, e.g., high reversible capacity (640.8 mA h g-1at 0.1 A g-1), excellent cycling stability (500 cycles with respective capacity retention of over or nearly 100%), and good rate capability, representing a comparable lithium storage performance in reported phosphide-based anodes. More significantly, it shows excellent energy storage properties in lithium-ion full cells which can light up 85 red LEDs for over 3.2 h. This work offers an advanced electrode construction guidance of phosphorous-based anodes for the development of high-performance energy storage devices.

Single-cell RNA-seq dissects the intratumoral heterogeneity of triple-negative breast cancer based on gene regulatory networks.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high intratumoral heterogeneity. Recent studies revealed that TNBC patients might comprise cells with distinct molecular subtypes. In addition, gene regulatory networks (GRNs) constructed based on single-cell RNA sequencing (scRNA-seq) data have demonstrated the significance for decoding the key regulators. We performed a comprehensive analysis of the GRNs for the intrinsic subtypes of TNBC patients using scRNA-seq. The copy number variations (CNVs) were inferred from scRNA-seq data and identified 545 malignant cells. The subtypes of the malignant cells were assigned based on the PAM50 model. The cell-cell communication analysis revealed that the macrophage plays a dominant role in the tumor microenvironment. Next, the GRN for each subtype was constructed through integrating gene co-expression and enrichment of transcription-binding motifs. Then, we identified the critical genes based on the centrality metrics of genes. Importantly, the critical gene ETV6 was ubiquitously upregulated in all subtypes, but it exerted diverse roles in each subtype through regulating different target genes. In conclusion, the construction of GRNs based on scRNA-seq data could help us to dissect the intratumoral heterogeneity and identify the critical genes of TNBC.

Integrative Analysis of Regulatory Module Reveals Associations of Microgravity with Dysfunctions of Multi-body Systems and Tumorigenesis.

Previous studies have demonstrated that microgravity could lead to health risks. The investigation of the molecular mechanisms from the aspect of systems biology has not been performed yet. Here, we integratively analyzed transcriptional and post-transcriptional regulations based on gene and miRNA expression profiles in human peripheral blood lymphocytes cultured in modeled microgravity. Two hundred and thirty dysregulated TF-miRNA (transcription factor and microRNA) feed-forward loops (FFLs) were identified in microgravity. The immune, cardiovascular, endocrine, nervous and skeletal system subnetworks were constructed according to the functions of dysregulated FFLs. Taking the skeletal system as an example, most of genes and miRNAs in the subnetwork were involved in bone loss. In addition, several drugs have been predicted to have potential to reduce bone loss, such as traditional Chinese medicines Emodin and Ginsenoside Rh2. Furthermore, we investigated the relationships between microgravity and 20 cancer types, and found that most of cancers might be promoted by microgravity. For example, rectum adenocarcinoma (READ) might be induced by microgravity through reducing antigen presentation and suppressing IgA-antibody-secreting cells' migration. Collectively, TF-miRNA FFL might provide a novel mechanism to elucidate the changes induced by microgravity, serve as drug targets to relieve microgravity effects, and give new insights to explore the relationships between microgravity and cancers.

TUG1 knockdown inhibits the tumorigenesis and progression of prostate cancer by regulating microRNA-496/Wnt/ß-catenin pathway.

Our study aimed to further investigate the roles and molecular mechanisms of lncRNA taurine upregulated gene 1 (TUG1) in the development and progression of PC. RT-qPCR assay was carried out to measure expression of TUG1, miR-496, together with ß-catenin, cyclin D1 and c-myc. Protein levels of ß-catenin, cyclin D1 and c-myc were detected by western blot assay. Cell proliferative ability was assessed by colony formation assay and CCK-8 assay. Cell migratory and invasive capacities were evaluated by Transwell migration and invasion assay. The interaction between miR-496 and TUG1 was explored by bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay. Mouse xenograft experiments were performed to further investigate the roles and molecular basis of TUG1 in the tumorigenesis of PC in vivo. TUG1 was highly expressed in PC tissues and cells (DU145 and PC3). TUG1 knockdown inhibited proliferation, migration and invasion in DU145 and PC3 cells. Moreover, TUG1 suppressed miR-496 expression by direct interaction. TUG1 overexpression abrogated miR-96-mediated antiproliferation, anti-migration and anti-invasion effects in DU145 and PC3 cells. TUG1 knockdown inactivated Wnt/ß-catenin signaling pathway by upregulating miR-496 in DU145 and PC3 cells. Additionally, TUG1 knockdown inhibited DU145 cells derived PC xenograft growth by upregulating miR-496 and inactivating Wnt/ß-catenin signaling in vivo. TUG1 knockdown suppressed PC cell proliferation, migration and invasion in vitro and curbed PC xenograft growth in vivo by regulating miR-496/Wnt/ ß-catenin signaling pathway, deepening our understanding on etiology of PC.