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Purpose: Previous studies have reported that miR-30d-5p gene expression can inhibit tumor proliferation, but its mechanism has not been fully elucidated. Methods: Based on previous findings, TGF-β1 was used to induce epithelial mesenchymal transformation in A549 cells. The expression levels of DUSP-1, E-cadherin and Vimentin were detected by Western blot. mRNA expression levels of DUSP-1, E-cadherin and Vimentin were determined by RT-qPCR. The expression level of miR-30d-5p was determined by RT-qPCR. Results: The induction effect of TGF-β1 could be reversed by the intervention of miR-30d-5p in A549 cells. miRNA inhibition experiment showed that miR-30d-5p inhibitor could effectively inhibit the expression of miR-30d-5p in A549 cells. After miR-30d-5p intervention, TGF-β1 was reversed on EMT-related genes (Dusp-1, E-cadherin, Vimentin). Conclusion: TGF-β1 can induce epithelial mesenchymal transformation of A549 cells, and miR-30d-5p may be a key regulatory mechanism in regulating gene and protein expression of TGF-β1-mediated DUSP-1, E-cadherin and Vimentin. This provides a new perspective for understanding the anti-tumor effect of miR-30d-5p gene.

The pathogenesis of rheumatoid arthritis (RA) remains elusive. The initiation of joint degeneration is characterized by the loss of self-tolerance in peripheral joints. Ferroptosis, a form of regulated cell death, holds significant importance in the pathophysiology of inflammatory arthritis, primarily due to iron accumulation and the subsequent lipid peroxidation.The present study investigated the association between synovial lesions and ferroptosis-related genes using previously published data from rheumatoid patients. Transcriptome differential gene analysis was employed to identify ferroptosis-related differentially expressed genes (FRDEGs). To validate FRDEGs and screen hub genes, we used weighted gene co-expression network analysis (WGCNA) and receiver operating characteristic (ROC) curves. Subsequently, immune infiltration analysis and single cell analysis were conducted to investigate the relationship between various synovial tissues cells and FRDEGs. The findings were further confirmed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemical staining, and immunofluorescence techniques.Upon intersecting DEGs with ferroptosis-related genes, we identified a total of 104 FRDEGs. Through the construction of a protein-protein interaction (PPI) network, we pinpointed the top 20 most highly concentrated genes as hub genes. Subsequent analyses using ROC curve and WGCNA validated eight FRDEGs: TIMP1, JUN, EGFR, SREBF1, ADIPOQ, SCD, AR, and FABP4. Immuno-infiltration analyses revealed significant infiltration of immune cell in RA synovial tissues and their correlations with the FRDEGs. Notably, TIMP1 demonstrated a positive correlation with various immune cell populations. Single-cell sequencing date of RA synovial tissue revealed predominant expression of TIMP1 is in fibroblasts. RT–qPCR, immunohistochemistry, and immunofluorescence analyses confirmed significant upregulation of TIMP1 at both mRNA and protein levels in RA synovial tissues and fibroblast-like synoviocytes (FLS).The findings provide novel insights into pathophysiology of peripheral immune tolerance deficiency in RA. The dysregulation of TIMP1, a gene associated with ferroptosis, was significantly observed in RA patients, suggesting its potential as a promising biomarker and therapeutic target.

The eighth experiment of the SINQ Target Irradiation Program (STIP-VIII) included a total of 941 specimens from 25 steels, 8 zircaloys, 6 tungsten based alloys (W-alloys) and 2 silicon carbide (SiC) composites. Specimens were prepared in 2016 and 2017. Irradiation was carried out in SINQ Target-13 in two periods: June 26 to December 21, 2018 and July 30 to December 23, 2020. The total proton charge received by Target-13 is 7.8 Ah, corresponding to 1.75×1023 protons. The irradiated specimens were unpacked in 2022 and 2023 and more than 98 % of the specimens were recovered. The specimens were irradiated at temperatures between 100 and 450 °C. The maximum doses are 10.4 dpa for steels, 14.8 dpa for zircaloys, 11.5 dpa for W-alloys, and 3.5 dpa for SiC composites. The He-to-dpa ratio is in the range of 22–42 appm/dpa for steels, 13–16 appm/dpa for zircaloys, 30–36 appm/dpa for W-alloys and 90–125 appm/dpa for SiC composites.

Recently, extreme wildfires occur frequently around the world and emit substantial brown carbon (BrC) into the atmosphere, whereas the molecular compositions and photochemical evolution of BrC remain poorly understood. In this work, primary smoke aerosols were generated from wood smoldering, and secondary smoke aerosols were formed by the OH radical photooxidation in an oxidation flow reactor, where both primary and secondary smoke samples were collected on filters. After solvent extraction of filter samples, the molecular composition of dissolved organic carbon (DOC) was determined by Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS). The molecular composition of dissolved BrC was obtained based on the constraints of DOC formulae. The proportion of dissolved BrC fractions accounted for approximately 1/3–1/2 molecular formulae of DOC. The molecular characteristics of dissolved BrC showed higher levels of carbon oxidation state, double bond equivalents, and modified aromaticity index than those of DOC, indicating that dissolved BrC fractions were a class of organic structures with relatively higher oxidation state, unsaturated and aromatic degree in DOC fractions. The comparative analysis suggested that aliphatic and olefinic structures dominated DOC fractions (contributing to 70.1%-76.9%), while olefinic, aromatic, and condensed aromatic structures dominated dissolved BrC fractions (contributing to 97.5%-99.9%). It is worth noting that dissolved BrC fractions only contained carboxylic-rich alicyclic molecules (CRAMs)-like structures, unsaturated hydrocarbons, aromatic structures, and highly oxygenated compounds. CRAMs-like structures were the most abundant species in both DOC and dissolved BrC fractions. Nevertheless, the specific molecular characteristics for DOC and dissolved BrC fractions varied with subgroups after aging. The results highlight the similarities and differences in the molecular compositions and characteristics of DOC and dissolved BrC fractions with aging. This work will provide insights into understanding the molecular composition of DOC and dissolved BrC in smoke.

Background: Glioma is the most frequent type of malignancy that may damage the brain with high morbidity and mortality rates and patients' prognoses are still dismal. Ferroptosis, a newly uncovered mode of programmed cell death, may be triggered to destroy glioma cells. Nevertheless, the significance of ferroptosis-related genes (FRGs) in predicting prognosis in glioma individuals is still a mystery. Methods: The CGGA (The Chinese Glioma Atlas), GEO (Gene Expression Omnibus), and TCGA (The Cancer Genome Atlas) databases were all searched to obtain the glioma expression dataset. First, TCGA was searched to identify differentially expressed genes (DEGs). This was followed by a machine learning algorithm-based screening of the glioma's most relevant genes. Additionally, these genes were subjected to Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional enrichment analyses. The chosen biological markers were then submitted to single-cell, immune function, and gene set enrichment analysis (GSEA). In addition, we performed functional enrichment and Mfuzz expression profile clustering on the most promising biological markers to delve deeper into their regulatory mechanisms and assess their clinical diagnostic capacities. Results: We identified 4444 DEGs via differential analysis and 564 FRGs from the FerrDb database. The two were subjected to intersection analysis, which led to the discovery of 143 overlapping genes. After that, glioma biological markers were identified in fourteen genes by the use of machine learning methods. In terms of its use for clinical diagnosis, SMG9 stands out as the most significant among these biomarkers. Conclusion: In light of these findings, the identification of SMG9 as a new biological marker has the potential to provide information on the mechanism of action and the effect of the immune milieu in glioma. The promise of SMG9 in glioma prognosis prediction warrants more study.

Objectives: This study aimed to assess the feasibility of the home-based kyphosis-specific exercises among Chinese older adults with different exercise habits and explore its potential effects on reducing the kyphosis angle and improving physical performance. Methods: A single-group, pre-and post-test design was conducted according to CONSORT 2010 statement: extension for pilot and feasibility trials. A total of 20 participants aged ≥60 with thoracic hyperkyphosis and rehabilitation potential were recruited from four local communities in Wuhan, China. Participants underwent a six-week home-based kyphosis-specific exercises intervention that included warm-up, muscle strengthens, spinal alignment, spinal mobility and flexibility, and cool down five sections (22 exercises). The intervention involved seven 1-h group classes and 35 times daily home practice with identical content. At pre- and post-intervention, the participants' kyphosis angle in two standing postures, static balance, dynamic balance, cardiopulmonary function, dynamic gait assessment, pain, and self-image were assessed and compared. Feasibility was assessed by group class attendance, home practice adherence, and participant evaluations. Results: All participants completed group classes and >75% home practice. Post-intervention, the participant’s kyphosis angle in relaxed and best-standing postures was changed by −12.0° (−15.5°, −4.0°) (Z = − 3.98, P

Background: Diabetic kidney disease (DKD) is a common and potentially fatal consequence of diabetes. Chronic renal failure or end-stage renal disease may result over time. Numerous studies have demonstrated the function of the microbiota in health and disease. The use of advanced urine culture techniques revealed the presence of resident microbiota in the urinary tract, undermining the idea of urine sterility. Studies have demonstrated that the urine microbiota is related with urological illnesses; nevertheless, the fundamental mechanisms by which the urinary microbiota influences the incidence and progression of DKD remain unclear. The purpose of this research was to describe key characteristics of the patients with DKD urinary microbiota in order to facilitate the development of diagnostic and therapeutic for DKD. Methods: We evaluated the structure and composition of the microbiota extracted from urine samples taken from DKD patients (n = 19) and matched healthy controls (n = 15) using 16S rRNA gene sequencing. Meanwhile, serum metabolite profiles were compared using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Associations between clinical characteristics, urine microbiota, and serum metabolites were also examined. Finally, the interaction between urine microbiota and serum metabolites was clarified based on differential metabolite abundance analysis. Results: The findings indicated that the DKD had a distinct urinary microbiota from the healthy controls (HC). Taxonomic investigations indicated that the DKD microbiome had less alpha diversity than a control group. Proteobacteria and Acidobacteria phyla increased in the DKD, while Firmicutes and Bacteroidetes decreased significantly (P

Among urological cancers, renal cancer has the highest fatality rate. In a previous pan-cancer study of the METTL family, we observed a stronger association between the METTL family members and the risk of renal cancer compared to other cancers. Among these members, METTL7A, a potential methyltransferase, was identified as a protective factor, although its role and mechanism in renal cancer remain unclear. In this study, we utilized public databases to examine the expression of METTL7A in renal cancer tissues and normal tissues and found that METTL7A expression was much lower in renal cancer tissues. We also noticed a link between low METTL7A expression and poor prognosis for patients. According to the results of our functional enrichment analysis, METTL7A may have a role in immunological functions in renal cancer. METTL7A expression was strongly linked with the degrees of immune cell infiltration and expression of numerous immunological components. METTL7A had significantly different effects on the survival times of renal cancer patients with high or low immune infiltration. Our findings suggest that METTL7A may be used as both a prognostic biomarker and an immunological target for kidney cancer. In conclusion, our study sheds light on the importance of METTL7A in renal cancer and emphasizes the potential of targeting METTL7A as a novel therapeutic strategy for kidney cancer.

Conical picks are widely used as cutting tools in shearers and roadheaders, and the mean cutting force (MCF) is one of the important parameters affecting conical pick performance. As MCF depends on a number of parameters and due to that the existing empirical and theoretical formulas and numerical modelling are not sufficient enough and reliable to predict MCF in a proficient manner. So, in this research, a novel intelligent model based on a random forest algorithm (RF) and a heuristic algorithm called the salp swarm algorithm (SSA) have been applied to determine the optimal hyper-parameters in RF, and root mean square error is used as a fitness function. A total of 188 data samples including 50 rock types and seven parameters (tensile strength of the rock σt, compressive strength of the rock σc, cone angle θ, cutting depth d, attack angle γ, rake angle α and back-clearance angle β) were collected to develop an SSA-RF model for mean cutting force prediction. The prediction results of the SSA-RF model were compared with seven influential formulas and four classical models, such as random forest, extreme learning machine, support vector machine and radial basis function neural network. The mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE) and Pearson correlation coefficient (R2) were employed as evaluation indexes to compare the capability of different predicting models. The MAE (0.509 and 0.996), RMSE (0.882 and 1.165), MAPE (0.146 and 0.402) and R2 (0.975 and 0.910) values between measured and predicted MCF for training and testing phases of the SSA-RF model clearly demonstrate the superiority in prediction compared to the other tools. A sensitivity analysis has also been performed to understand the influence of each input parameter on MCF, which indicates that σc, d and σt are the most important variables for MCF prediction.

In this study, a post-irradiation examination of pure tungsten (W) and tantalum (Ta) specimens irradiated at the Swiss Spallation-Neutron Source is conducted. W is used as a potential candidate for a solid spallation-target material owing to its favorable properties, namely, high neutron yield, good thermal conductivity, and low thermal-expansion coefficient. However, W also suffers from several disadvantages such as poor corrosion resistance to water coolant and irradiation embrittlement. To improve these properties, cladding technologies using Ta for W alloys have been developed. In the present study, we investigated the irradiation effects on two tungsten materials—poly-crystal W (W-Poly) and single-crystal W (W-Sin)—along with pure polycrystalline Ta. The tensile-test results revealed that W-Poly exhibited almost no ductility after irradiation of 10.2–35.0 displacement per atom (dpa). W-Sin was irradiated up to 10.2 dpa and demonstrated 6% of total elongation (TE). With regard to Ta, TE decreased based on the increase in irradiation, reaching almost zero at doses of more than 10.3 dpa. For pure Ta, grain size was one of the key parameters in investigating the irradiated-material properties.

Non-small cell lung cancer (NSCLC) has a high morbidity and mortality, and it is imperative to explore the latent pathogenesis mechanism of NSCLC progression to find potential prognostic biomarkers and therapeutic targets. The present study aimed to explore the biological function of circSHKBP1 in NSCLC. circSHKBP1 was found to be upregulated in NSCLC tissues and cell lines and was enriched in exosomes derived from NSCLC cells. Exosomal circSHKBP1 enhanced the proliferation, migration, invasion, and stemness of NSCLC cells. miRNA-1294 was identified as a target for circSHKBP1, and circSHKBP1 upregulated PKM2 expression by sponging miR-1294. Exosomal circSHKBP1 regulated glycolysis through PKM2 in a HIF-1α-dependent manner in NSCLC cells and promoted M2 polarization and macrophage recruitment. Moreover, exosomal circSHKBP1 promoted NSCLC cell growth, metastasis, and M2 infiltration in vivo. Thus, exosomal circSHKBP1 participated in the progression of NSCLC via the miR-1294/PKM2 axis. circSHKBP1 may be potential biomarker for the diagnosis and treatment of NSCLC.

Systemic lupus erythematous (SLE) is a complex chronic autoimmune disease with difficult early treatment and accurate diagnosis. Circulating exosomes containing proteins, lipids and nucleic acids can be ideal diagnostic biomarkers and disease management strategies for SLE. Our aim was to examine the unique expression profiles of circulating exosomal miRNAs and proteins in patients with SLE patients.Using RNA-sequencing and proteomic approaches, we compared the expression patterns of exosomal miRNAs and proteins in the plasma of SLE patients and healthy subjects, and discussed the underlying signaling network of circulating exosomes. We also summarize common molecules (miRNAs and proteins) and pathways shared by our plasma exosomes, as well as previously reported data (PBMC, T cells, B cells and plasma).We identified groups of differentially expressed exosomal miRNAs and proteins in the plasma of SLE patients and healthy controls. We obtained consensus molecules (39 miRNAs, 14 proteins) and 21 signaling pathways that are common in our current study and previous reports.Common molecules (miRNAs and proteins) and pathways shared by our plasma exosomes data and other circulating components data reported previously indicate their potential application in the clinical treatment and diagnosis of SLE disease.

The excessive and ectopic pulmonary artery smooth muscle cells (PASMCs) are crucial to the pathogenesis of pulmonary arteriole (PA) remodeling in pulmonary arterial hypertension (PAH). We previously found that microRNA (miR)-30a was significantly increased in acute myocardial infarction (AMI) patients and animals, as well as in cultured cardiomyocytes after hypoxia, suggesting that it might be strongly associated with hypoxia-related diseases. Here, we investigated the role of miR-30a in the PASMC remodeling of PAH. The expression of miR-30a was higher in the serum of PAH patients compared with healthy controls. miR-30a was mainly expressed in PAs and was increased in PASMCs after hypoxia, mediating the downregulation of p53 tumor suppressor protein (P53). Genetic knockout of miR-30a effectively decreased right ventricular (RV) systolic pressure (RVSP), PA, and RV remodeling in the Su5416/hypoxia-induced and monocrotaline (MCT)-induced PAH animals. Additionally, pharmacological inhibition of miR-30a via intratracheal liquid instillation (IT-L) delivery strategy showed high efficiency, which downregulated miR-30a to mitigate disease phenotype in the Su5416/hypoxia-induced PAH animals, and these beneficial effects could be partially reduced by simultaneous P53 inhibition. We demonstrate that inhibition of miR-30a could ameliorate experimental PAH through the miR-30a/P53 signaling pathway, and the IT-L delivery strategy shows good therapeutic outcomes, providing a novel and promising approach for the treatment of PAH.

Nowadays, among all urinary system cancers, the mortality of kidney cancer (KC) has risen to the first, and the incidence has been keeping on the third. Many recent studies have demonstrated that m6A modification regulated by the methyltransferases (writers) is closely related to the tumorigenesis of multiple cancers. In our previous study, we found that the methyltransferase METTL5 had a stronger association with the hazard ratio of KC more than most tumors, indicating its special function in carcinogenesis of KC. Until now, the expression, functions and mechanism of METTL5 in KC are still unclear. In this study, we analyzed the mRNA expression of METTL5 using the data sets from public databases, and revealed that the METTL5 expression was significantly up-regulated in tumor tissues of kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) compared to normal tissues. Also, the METTL5 expression was correlated with the tumor stage and grade, indicating the potential involvement of METTL5 in tumor progression. Additionally, the higher expression of METTL5 predicted poorer prognosis of KIRC and KIRP patients. Subsequently, we revealed that the functions of METTL5 in KIRC might be related to immune modulation, because its co-expressed gene were enriched in immune-relevant pathways including Th17 cell differentiation, Th1 and Th2 cell differentiation, and phosphatidylinositol 3-kinase activity. Next, we disclosed that the METTL5 expression was correlated to the microenvironment score and immune score of KIRC and KIRP, and associated with the infiltration ratios of 25 types of immune cells. Besides, we demonstrated a wide difference of the METTL5's effect on the survival of patients with high and low immune infiltration, further suggesting METTL5 might affect tumor development via modulating the immune microenvironment. The findings of our study provide a novel potential prognostic biomarker and immune drug target for KC.

Background: Sodium glucose cotransporter 2 (SGLT2) inhibitors originally developed for the treatment of type 2 diabetes are clinically very effective drugs halting chronic kidney disease progression. The underlying mechanisms are, however, not fully understood. Methods: We generated single-cell transcriptomes of kidneys from rats with 5/6 nephrectomy before and after SGLT2 inhibitors treatment by single-cell RNA sequencing. Findings: Empagliflozin treatment decreased BUN, creatinine and urinary albumin excretion compared to placebo by 39.8%, 34.1%, and 55%, respectively (p

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Idiopathic MN (IMN), one of the forms of MN, usually has an unknown etiology. IMN is described as an autoimmune disease, and its pathogenesis is quite complex. The discovery of the M-type phospholipase A2 receptor (PLA2R) plays an important role in promoting our understanding of IMN, although the exact mechanisms of its occurrence and development are still not completely clear. Other target antigens have been discovered one after another, as considerable progress has been made in the molecular pathomechanisms of IMN. Here, we review the findings about the target antigens associated with IMN in recent years. It is hoped that this article can provide researchers with some scientific issues or innovative ideas for future studies of IMN, which will provide clinicians with more knowledge about further improving their abilities to provide better medical care for IMN patients.

Summary: Ferroptosis is a type of programmed cell death potentially playing an important role in colorectal cancer (CRC) development. However, comprehensive investigations toward ferroptosis in human CRC are lacking. Here, we performed multiple investigations on cancer and para-cancer tissues. We demonstrated that the changes of structural variation and chromatin accessibility in CRC were more associated with the altered mRNA expression of ferroptosis-related genes (FRGs), and the expression of CDKN2A, GPX4, ALOXE3, and LINC00336 was related to the overall survival rates. Subsequently, we revealed that CYBB and YAP1 were potentially the hub genes, and that HSF1 and STAT2 were potentially FRGs’ upstream transcription factors. Finally, we depicted the crosstalk between ferroptosis and necrosis, autophagy, and apoptosis. Based on multi-dimensional analyses, we characterized ferroptosis, probable core genes, and the upstream regulators in human CRC. The findings here may improve our understanding of ferroptosis in CRC and provide new opportunities for clinical diagnosis and treatment.

Summary: The spine has essential roles in supporting body weight, and passaging the neural elements between the body and the brain. In this study, we used integrated single-cell RNA sequencing and single-cell transposase-accessible chromatin sequencing analyses to reveal the cellular heterogeneity, lineage, and transcriptional regulatory network of the developing human spine. We found that EPYC + HAPLN1+ fibroblasts with stem cell characteristics could differentiate into chondrocytes by highly expressing the chondrogenic markers SOX9 and MATN4. Neurons could originate from neuroendocrine cells, and MEIS2 may be an essential transcription factor that promotes spinal neural progenitor cells to selectively differentiate into neurons during early gestation. Furthermore, the interaction of NRP2_SEMA3C and CD74_APP between macrophages and neurons may be essential for spinal cord development. Our integrated map provides a blueprint for understanding human spine development in the early and midgestational stages at single-cell resolution and offers a tool for investigating related diseases.

The incidence and mortality of colon cancer in China are increasing each year. At present, treatment selection for colon cancer patients mainly depends on imaging results, which require a large number of radiologists to interpret. In China, there is a shortage and uneven distribution of experienced radiologists, which leads to delays and bias in the evaluation of imaging data. Based on these considerations, the Colorectal Surgery Group of the Surgery Branch of the Chinese Medical Association in collaboration with experts at Beihang University has independently developed an artificial intelligence (AI)-based recognition system for the preoperative determination of colon cancer stage to partially replace the work of and relieve the pressure on radiologists. These guidelines aim to standardize the use of AI-based recognition systems in the preoperative staging of colon cancer and guide their clinical application.

Objective: To enhance the bioactivity of polyetheretherketone (PEEK) while maintain its mechanical strengths. Methods: Suspension coating and melt bonding. Results: Silicon nitride (Si3N4, SN) coating lead to higher surface roughness, hydrophilicity and protein absorption; SN coating could slowly release Si ion into simulated body fluid (SBF), which caused weak alkaline of micro-environment owing to the slight dissolution of SN; SN coating resulted in the improvements of adhesion, proliferation, differentiation and gene expressions of MC3T3-E1 cells in vitro; SN coating of PEEK with bioactive SN coating (CSNPK) obviously promoted bone regeneration and osseointegration in vivo. Conclusions: CSNPK with SN coating as bone implant might be a promising candidate for orthopedic implants. The Translational Potential of this Article: The silicon nitride-coated polyetheretherketone (CSNPK) prepared in this article could induce MC3T3-E1 cells adhesion, proliferation and differentiation in vitro; it could also induce bone regeneration in bone defect in vivo, which indicate its good cytocompatibility and biocompatibility. If the raw materials are medical grade, and preparation process as well as production process of this article are further improved, it will have great translational potential.

Systemic lupus erythematosus (SLE) is a heterogeneous, autoimmune disease that can affect multiple organs and systems such as skin, joints, kidneys, hematologic system or central nervous system. Women of childbearing age are the predominate population affected by SLE. In this study, we generated an iPS cell line from a 30-year-old female who was pregnant with a gestational age of 27 weeks and diagnosed with severe preeclampsia, SLE and psoriasis. This patient-specific iPSC line will be useful to create the specific disease model of systemic lupus erythematosus to elucidate the pathological mechanisms and develop drug screening.

The adipokine chemerin has been considered an important regulator of tumor immune surveillance. Chemerin recruits leukocytes through the receptor CMKLR1 to improve clinical outcomes of tumors and overall patient survival, but the role of GPR1 in tumors has not been widely investigated. Here, we found that GPR1 expression is elevated in breast cancer—especially triple-negative breast cancer (TNBC) tissues and cell lines. Herein, we screened a phage display peptide library to identify LRH7-G5, a peptide antagonist that blocks chemerin/GPR1 signaling. This peptide performed as an anticancer agent to suppress the proliferation of the TNBC cell lines MDA-MB-231 and HCC1937 but has little effect on T47D cells. LRH7-G5 treatment significantly blocked tumor growth in a TNBC cell-bearing orthotopic mouse model. Last, our results showed that this peptide’s antitumor role is mediated through the PI3K/AKT signaling pathway. In conclusion, these data collectively suggest that the chemerin receptor GPR1 is a novel target for controlling TNBC progression and establish peptide LRH7-G5 as a new therapeutic agent for suppressing TNBC tumor growth.

Background: Duodenal-jejunal bypass (DJB) surgery can improve type 2 diabetes (T2D) dramatically. Accumulating evidence implicates deficiency of hepatic adiponectin signaling as a contributor to gluconeogenesis disorders, and some microRNAs (miRNAs) regulate adiponectin receptors (AdipoR1, AdipoR2). We investigated the effects of DJB on hepatic gluconeogenesis, lipid metabolism, and inflammation as well as the effects of miRNA-320 (AdipoR1-targeting miRNA) on DJB-induced T2D amelioration., Objectives: To investigate the essential role of miRNAs in regulation of adiponectin signaling by targeting AdipoR1 in DJB and the underlying mechanisms., Setting: University Hospital, China., Methods: We studied hepatic adiponectin signaling changes and hepatic miRNAs involved in a rat model of DJB. We investigated the effects of miR-320 on AdipoR1 signaling in buffalo rat liver cell lines. Liver tissues and glucose tolerance tests were analyzed in DJB rats injected with lentivirus encoding a miR-320 mimic., Results: Transfection with a miR-320 mimic reduced AdipoR1 protein levels and inhibited downstream adiponectin signaling; transfection with a miR-320 inhibitor elicited the opposite effects. A luciferase assay confirmed that miR-320 binds to the 3'-untranslated regions of AdipoR1. Global upregulation of miR-320 expression in DJB rats showed impaired gluconeogenesis, lipid metabolism, and relatively higher expression of inflammation markers., Conclusion: miR-320 regulates the adipoR1-mediated amelioration of T2D in DJB and should be explored as a potential target for T2D treatment., (Copyright © 2018. Published by Elsevier Inc.)

In this study, 17 Y-STR loci(AmpFISTR(®)Y-filerTM)-DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635, DYS392, Y-GATA H4, DYS437, DYS438, DYS448 were analyzed in 424 unrelated males from Luzhou Han ethnic group, Southwest China. 365 haplotypes were observed. The discrimination capacity was 0.8608 and the haplotype diversity was 0.9992., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)