Microphthalmia transcription factor (MiT) family translocation renal cell carcinoma (tRCC) is a rare type of kidney cancer, which is not well characterized. Here we show the comprehensive proteogenomic analysis of tRCC tumors and normal adjacent tissues to elucidate the molecular landscape of this disease. Our study reveals that defective DNA repair plays an important role in tRCC carcinogenesis and progression. Metabolic processes are markedly dysregulated at both the mRNA and protein levels. Proteomic and phosphoproteome data identify mTOR signaling pathway as a potential therapeutic target. Moreover, molecular subtyping and immune infiltration analysis characterize the inter-tumoral heterogeneity of tRCC. Multi-omic integration reveals the dysregulation of cellular processes affected by genomic alterations, including oxidative phosphorylation, autophagy, transcription factor activity, and proteasome function. This study represents a comprehensive proteogenomic analysis of tRCC, providing valuable insights into its biological mechanisms, disease diagnosis, and prognostication.

To identify DLX3 variants in a Chinese family with typical clinical manifestations of tricho-dento-osseous syndrome (TDO).

Chromosomal duplication at the Xq28 region including the MECP2 gene, share consistent clinical phenotypes and a distinct facial phenotype known as MECP2 duplication syndrome. The typical clinical features include infantile hypotonia , mild dysmorphic features, a broad range of neurodevelopmental disorders, recurrent infections, and progressive spasticity.

Long non-coding RNAs (lncRNAs) are involved in developing hepatocellular carcinoma (HCC). The present study explored the role of lncRNA LINC01194, which is upregulated in HCC tissues and might be a vital regulator in HCC progression. Levels of LINC01194, microRNA (miR)-655-3p, and SMAD family member 5 (SMAD5) were assessed using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The bioactivity of Huh-7 cells was assessed using cell counting kit-8 and transwell assays and flow cytometry. Western blotting was conducted to measure the expression of invasion- and apoptosis-related proteins. The relationships between lncRNA LINC01194 and miR-655-3p, and miR-655-3p and SMAD5 were predicted using StarBase and TargetScan, and further verified using a dual-luciferase reporter assay. LINC01194 was overexpressed in HCC cells and in clinical samples. ILINC01194 silencing suppressed proliferation and migration; however, it promoted apoptosis in HCC cell lines. We also confirmed that miR-655-3p could bind to LINC01194, and miR-655-3p was downregulated in HCC. The upregulation of miR-655-3p suppressed HCC cell invasion and migration, and enhanced the number of apoptotic cells. SMAD5, which was overexpressed in HCC cell lines, was directly targeted by miR-655-3p. Therefore, LINC01194 promoted HCC development by decreasing miR-655-3p expression and may serve as a promising therapeutic target for HCC patients.

Hypophosphatasia (HPP) is a rare hereditary systemic disease that is characterized by defective bone and/or dental mineralization, and is caused by mutations in the alkaline phosphatase gene (ALPL). The present study investigated the ALPL mutation in a Chinese Han family with HPP and studied the pathogenesis of the mutations of the ALPL gene. DNA was extracted from peripheral venous blood of the family members. Sanger sequencing was used to screen the mutations. Associations between pathogenesis for both mutations were analyzed by bioinformatics, subcellular localization, measurement of enzyme activity and western blotting. Sanger sequencing revealed the compound heterozygous mutations c.203C>T (p.T68M) and c.571G>A (p.E191K). The mutations were located at exon 4 and 6 of the ALPL gene and were predicted by Polyphen-2 analysis to be harmful. Protein analysis indicated a decrease in mature protein production and lower enzyme activity in 293T cells transfected with plasmids carrying the mutations. The ALPL gene was cloned into the pcDNA3.1(+) vector and mutant plasmids ALPL-pT68M and ALPL-pE191K were constructed. Immunofluorescence observed in cells transfected with the ALPL-pE191K mutant plasmid was mainly located in the cell membrane. However, staining in the cytoplasm was increased compared with the wild type, and almost no fluorescence was identified in 293T cells transfected with the ALPL-pT68M mutant plasmid. The present findings demonstrated that the compound heterozygous c.571G>A and c.203C>T mutations may contribute to childhood HPP by resulting in mislocalization, decreased protein expression and loss of enzyme activity in a Han Chinese family. The results of the current study may provide insights into the potential molecular mechanism of HPP.

Phospholipid-hydrolyzing enzymes include members of the phospholipase C (PLC) family that play important roles in regulating plant growth and responding to stress. In the present study, a systematic in silico analysis of the wheat PLC gene family revealed a total of 26 wheat PLC genes (TaPLCs). Phylogenetic and sequence alignment analyses divided the wheat PLC genes into 2 subfamilies, TaPI-PLC (containing the typical X, Y, and C2 domains) and TaNPC (containing a phosphatase domain). TaPLC expression patterns differed among tissues, organs, and under abiotic stress conditions. The transcript levels of 8 TaPLC genes were validated through qPCR analyses. Most of the TaPLC genes were sensitive to salt stress and were up-regulated rapidly, and some were sensitive to low temperatures and drought. Overexpression of TaPI-PLC1-2B significantly improved resistance to salt and drought stress in Arabidopsis, and the primary root of P1-OE was significantly longer than that of the wild type under stress conditions. Our results not only provide comprehensive information for understanding the PLC gene family in wheat, but can also provide a solid foundation for functional characterization of the wheat PLC gene family.

The U-box E3 (PUB) family genes encode the E3 ubiquitin ligase enzyme, which determines substrate specific recognition during protein ubiquitination. They are widespread in plants and are critical for plant growth, development, and response to external stresses. However, there are few studies on the functional characteristic of PUB gene family in the important staple crop, maize (Zea mays L.). In this study, the PUB gene in maize was aimed to identify and classify through whole-genome screening. Phylogenetic tree, gene structure, conserved motif, chromosome location, gene duplication (GD), synteny, and cis-acting regulatory element of PUB member were analyzed. The expression profiles of ZmPUB gene family in maize during development and under abiotic stress and hormones treatment were analyzed by the RNA-seq data. A total of 79 PUB genes were identified in maize genome, and they were stratified into seven categories. There were 25 pairs of segmental duplications (SD) and 1 pair of tandem duplication (TD) identified in the maize PUB gene family. A close relationship was observed between the monocot plant maize and rice in PUB gene family. There were 94 kinds of cis-acting elements identified in the maize PUB gene family, which included 46 biotic- and abiotic-responsive elements, 19 hormone-responsive elements, 13 metabolic and growth-related elements. The expression profiles of maize PUB gene family showed characteristics of tissue specificity and response to abiotic stress and hormones treatment. These results provided an extensive overview of the maize PUB gene family.

Normokalemic periodic paralysis (NormoKPP) of skeletal muscle is an autosomal dominant disorder caused by mutations in the gene encoding voltage-gated sodium channel protein type 4 subunit alpha (SCN4A), which leads to ion channel dysfunction. Little is known about the relationship between genotype and the clinical symptoms of NormoKPP. The present study aimed to evaluate the genetic variation in a large Chinese family with NormoKPP. The patients in this pedigree did not respond to saline treatment, but calcium gluconate treatment was effective.

Chestnut (Castanea mollissima) is a deciduous tree species with major economic and ecological value that is widely used in the study of floral development in woody plants due its monoecious and out-of-proportion characteristics. Squamosa promoter-binding protein-like (SPL) is a plant-specific transcription factor that plays an important role in floral development. In this study, a total of 18 SPL genes were identified in the chestnut genome, of which 10 SPL genes have complementary regions of CmmiR156. An analysis of the phylogenetic tree of the squamosa promoter-binding protein (SBP) domains of the SPL genes of Arabidopsis thaliana, Populus trichocarpa, and C. mollissima divided these SPL genes into eight groups. The evolutionary relationship between poplar and chestnut in the same group was similar. A structural analysis of the protein-coding regions (CDSs) showed that the domains have the main function of SBP domains and that other domains also play an important role in determining gene function. The expression patterns of CmmiR156 and CmSPLs in different floral organs of chestnut were analyzed by real-time quantitative PCR. Some CmSPLs with similar structural patterns showed similar expression patterns, indicating that the gene structures determine the synergy of the gene functions. The application of gibberellin (GA) and its inhibitor (Paclobutrazol, PP333) to chestnut trees revealed that these exert a significant effect on the number and length of the male and female chestnut flowers. GA treatment significantly increased CmmiR156 expression and thus significantly decreased the expression of its target gene, CmSPL6/CmSPL9/CmSPL16, during floral bud development. This finding indicates that GA might indirectly affect the expression of some of the SPL target genes through miR156. In addition, RNA ligase-mediated rapid amplification of the 5' cDNA ends (RLM-RACE) experiments revealed that CmmiR156 cleaves CmSPL9 and CmSPL16 at the 10th and 12th bases of the complementary region. These results laid an important foundation for further study of the biological function of CmSPLs in the floral development of C. mollissima.

Physic nut (Jatropha curcas), an inedible oilseed plant, is among the most promising alternative energy sources because of its high oil content, rapid growth and extensive adaptability. Proteins encoded by MADS-box family genes are important transcription factors participated in regulating plant growth, seed development and responses to abiotic stress. However, there has been no in-depth research on the MADS-box genes and their roles in physic nut.

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome has been reported to be highly expressed in oral lesions with the potential for malignant development such as oral lichen planus (OLP). And the NLRP3 inflammasome can be activated by galectin-3 (Gal-3) in immune-mediated chronic inflammatory diseases. This study aimed to explore the inter-relationships among Gal-3, NLRP3 inflammasome, and OLP.

Objective: To compare the EuroQol-5D-3L (EQ-5D-3L) and the Short Form-6D (SF-6D) utility scores in family caregivers (FCs) of colorectal cancer (CRC) patients. Method: This study was performed on FCs of CRC patients from three primary cancer centers in the capital city of the Heilongjiang province. The participants (FCs) who were enrolled, filled the EQ-5D-3L, along with the SF-6D questionnaire. Two tools were compared for their distribution, discriminant validity, agreement, and convergent validity along with known-groups validity. Result: Two hundred ninety-two FCs of CRC patients were enrolled. The score distribution of the SF-6D along with the EQ-5D-3L were not normal. A ceiling impact was seen in 31.8% of the FCs for EQ-5D-3L; however, none for the SF-6D. Good associations (Spearman's rho = 0.622, p < 0.01) and intraclass correlation coefficient (ICC 0.637 and average ICC 0.778) between the two scores were observed. The EQ-5D-3L yielded higher utility scores in contrast with the SF-6D in the better health subclass. The SF-6D distinguished better between excellent and good health statuses, with better effect size and relative efficiency statistics. Both tools showed good known-groups validity. Conclusion: The utility scores of SF-6D were remarkably lower relative to that of the EQ-5D-3L, but the difference may be clinically insignificant. However, the SF-6D may be superior because of the lack of ceiling impact. SF-6D exhibited a better convergent validity along with discrimination validity of excellent health condition and improved known-groups validity efficiency.

Triticum aestivum xylanase inhibitor (TaXI) gene plays an important role in plant defense. Recently, TaXI-III inhibitor has been shown to play a dual role in wheat resistance to Fusarium graminearum infection. Thus, identifying the members of the TaXI gene family and clarifying its role in wheat resistance to stresses are essential for wheat resistance breeding. However, to date, no comprehensive research on TaXIs in wheat (Triticum aestivum L.) has been conducted. In this study, a total of 277 TaXI genes, including six genes that we cloned, were identified from the recently released wheat genome database (IWGSC RefSeq v1.1), which were unevenly located on 21 chromosomes of wheat. Phylogenetic analysis divided these genes into six subfamilies, all the six genes we cloned belonged to XI-2 subfamily. The exon/intron structure of most TaXI genes and the conserved motifs of proteins in the same subfamily are similar. The TaXI gene family contains 92 homologous gene pairs or clusters, 63 and 193 genes were identified as tandem replication and segmentally duplicated genes, respectively. Analysis of the cis-acting elements in the promoter of TaXI genes showed that they are involved in wheat growth, hormone-mediated signal transduction, and response to biotic and abiotic stresses. RNA-seq data analysis revealed that TaXI genes exhibited expression preference or specificity in different organs and developmental stages, as well as in diverse stress responses, which can be regulated or induced by a variety of plant hormones and stresses. In addition, the qRT-PCR data and heterologous expression analysis of six TaXI genes revealed that the genes of XI-2 subfamily have double inhibitory effect on GH11 xylanase of F. graminearum, suggesting their potential important roles in wheat resistance to F. graminearum infection. The outcomes of this study not only enhance our understanding of the TaXI gene family in wheat, but also help us to screen more candidate genes for further exploring resistance mechanism in wheat.

Ferritin is one of the key proteins that regulate iron homeostasis and is widely available clinical biomarker of iron status. This study aimed to discuss the influence of serum ferritin (SF) on cardiovascular risk factors in the first-degree relatives with family history of type 2 diabetes (FHD).

Hip cartilage destruction is consistently observed in the non-traumatic osteonecrosis of femoral head (NOFH) and accelerates its bone necrosis. The molecular mechanism underlying the cartilage damage of NOFH remains elusive. In this study, we conducted a systematically comparative study of gene expression profiles between NOFH and osteoarthritis (OA). Hip articular cartilage specimens were collected from 12 NOFH patients and 12 controls with traumatic femoral neck fracture for microarray (n=4) and quantitative real-time PCR validation experiments (n=8). Gene expression profiling of articular cartilage was performed using Agilent Human 4×44K Microarray chip. The accuracy of microarray experiment was further validated by qRT-PCR. Gene expression results of OA hip cartilage were derived from previously published study. Significance Analysis of Microarrays (SAM) software was applied for identifying differently expressed genes. Gene ontology (GO) and pathway enrichment analysis were conducted by Gene Set Enrichment Analysis software and DAVID tool, respectively. Totally, 27 differently expressed genes were identified for NOFH. Comparing the gene expression profiles of NOFH cartilage and OA cartilage detected 8 common differently expressed genes, including COL5A1, OGN, ANGPTL4, CRIP1, NFIL3, METRNL, ID2 and STEAP1. GO comparative analysis identified 10 common significant GO terms, mainly implicated in apoptosis and development process. Pathway comparative analysis observed that ECM-receptor interaction pathway and focal adhesion pathway were enriched in the differently expressed genes of both NOFH and hip OA. In conclusion, we identified a set of differently expressed genes, GO and pathways for NOFH articular destruction, some of which were also involved in the hip OA. Our study results may help to reveal the pathogenetic similarities and differences of cartilage damage of NOFH and hip OA.

Ankylosing spondylitis (AS) is a chronic rheumatic and autoimmune disease. Little is known about the potential role of DNA methylation in the pathogenesis of AS. This study was undertaken to explore the potential role of DNA methylation in the genetic mechanism of AS.

Objective: This study aimed to assess the quantitative effects of short-term exposure of ambient nitrogen dioxide (NO₂) on respiratory disease (RD) mortality and RD hospital admission in China through systematic review and meta-analysis. Methods: A total of 29 publications were finally selected from searches in PubMed, Web of Science, CNKI and Wanfang databases. Generic inverse variance method was used to pool effect estimates. Pooled estimates were used to represent the increased risk of RD mortality and RD hospital admission per 10 μg/m³ increase in NO₂ concentration. Results: Positive correlations were found between short-term NO₂ exposure and RD in China. RD mortality and RD hospital admission respectively increased by 1.4% (95% CI: 1.1%, 1.7%) and 1.0% (95% CI: 0.5%, 1.5%) per 10 μg/m³ increase in NO₂ concentration. Differences were observed across geographic regions of China. The risk of RD mortality due to NO₂ was higher in the southern region (1.7%) than in the north (0.7%). Conclusions: Evidence was found that short-term exposure to NO₂ was associated with an increased risk of RD mortality and RD hospital admission in China and these risks were more pronounced in the southern regions of the country, due in part to a larger proportion of elderly persons with increased susceptibility to NO₂ in the population compared with the north.

This study aimed to investigate the reliability and validity of the Chinese version of the Patient Health Questionnaire (PHQ-15) in a tertiary hospital.

Placental dysfunction, including senescent changes, is associated with the pathogenesis of missed miscarriage, although the underlying mechanism is unclear. Increasing evidence indicates that placenta-specific miRNAs are packaged in extracellular vesicles (EVs) from placental syncytiotrophoblasts and are released into the maternal circulation. Aberrant cargos including miRNAs in placental EVs have been reported to be associated with the pathogenesis of complicated pregnancies. In this study, we compared the miRNA profiles in EVs derived from missed miscarriage and healthy placentae and investigated possible biological pathways which may be involved in senescence, one cause of missed miscarriage. The total concentration of RNA in placental EVs was not different between the two groups. However, there were 54 and 94 differentially expressed miRNAs in placental large and small EVs from missed miscarriage compared to EVs from healthy controls. The aberrantly expressed miRNAs seen in placental EVs were also observed in missed miscarriage placentae. Gene enrichment analysis showed that some of those differentially expressed miRNAs are involved in cellular senescence, endocytosis, cell cycle and endocrine resistance. Furthermore, transfection of trophoblasts by a single senescence-associated miRNA that was differentially expressed in placental EVs derived from missed miscarriage did not cause trophoblast dysfunction. In contrast, EVs derived from missed miscarriage placenta induced senescent changes in the healthy placenta. Our data suggested that a complex of placental EVs, rather than a few differentially expressed miRNAs in placental EVs derived from missed miscarriage placentae could contribute in an autocrine manner to placental senescence, one of the causes of missed miscarriage.

Macrophages sense changes in the extracellular matrix environment through the integrins and play a central role in regulation of the reparative response after myocardial infarction. Here we show that macrophage integrin α5 protects the infarcted heart from adverse remodeling and that the protective actions are associated with acquisition of an angiogenic macrophage phenotype. We demonstrate that myeloid cell- and macrophage-specific integrin α5 knockout mice have accentuated adverse post-infarction remodeling, accompanied by reduced angiogenesis in the infarct and border zone. Single cell RNA-sequencing identifies an angiogenic infarct macrophage population with high Itga5 expression. The angiogenic effects of integrin α5 in macrophages involve upregulation of Vascular Endothelial Growth Factor A. RNA-sequencing of the macrophage transcriptome in vivo and in vitro followed by bioinformatic analysis identifies several intracellular kinases as potential downstream targets of integrin α5. Neutralization assays demonstrate that the angiogenic actions of integrin α5-stimulated macrophages involve activation of Focal Adhesion Kinase and Phosphoinositide 3 Kinase cascades.