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The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3β signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury. The authors show that PEX3, as an essential regulator of peroxisome-related functions, promote myocardial regenerative repair through plasmalogen metabolism, facilitating plasma membrane localization of ITGB3 and activating the AKT/GSK3β signaling pathway. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens affecting the swine industry. In this report, a novel PRRSV strain SXht2012 was isolated from Shanxi province in China. To identify genetic characteristics of SXht2012, we conducted phylogenetic and homology analyses after sequencing its complete genome. The results revealed that SXht2012 belonged to NADC30-like strain and shared 91.3% nucleotide (nt) identity with strain NADC30. Notably, sequence alignment showed that a distinctive feature in the NSP2 region, where a 131-amino acid (aa) deletion was found in the hypervariable region (HVR). Additionally, variations were also detected in the GP5 protein, specifically in the decoy peptide, T cell peptide, and a potential glycosylation site (aa 32). Furthermore, we also found that SXht2012 was likely a recombination virus originating from NADC30-like and JXA1-like strains, and three recombination breakpoints were identified in the genome at nt positions 1516, 5280 and 6851, which correspond to the NSP2, NSP3, and NSP7 regions. Overall, these findings have significant implications for understanding the genetic variation and evolutionary dynamics of PRRSV strains. [ABSTRACT FROM AUTHOR]

The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition. We identify 4765 independent primary and 616 secondary cis-expression quantitative trait loci (cis-eQTLs) in the synovium and find that the eQTLs with multiple independent signals have stronger effects and heritability than single independent eQTLs. Integration of genome-wide association studies (GWASs) and eQTLs identifies 84 arthritis related genes, revealing 38 novel genes which have not been reported by previous studies using eQTL data from the GTEx project or immune cells. We further develop a method called eQTac to identify variants that could affect gene expression by affecting chromatin accessibility and identify 1517 regions with potential regulatory function of chromatin accessibility. Altogether, our study provides a comprehensive synovium multi-omics resource for arthritic diseases and gains new insights into the regulation of gene expression. Hundreds of arthritis-associated genetic variants have been identified but in most cases their functions remain unknown. Here the authors develop a resource to reveal the effects of variants on gene expression in human synovium, and identify arthritis-related genes. [ABSTRACT FROM AUTHOR]

Administration of CHK1-targeted anticancer therapies is associated with an increased cumulative risk of cardiac complications, which is further amplified when combined with gemcitabine. However, the underlying mechanisms remain elusive. In this study, we generated hiPSC-CMs and murine models to elucidate the mechanisms underlying CHK1 inhibition combined with gemcitabine-induced cardiotoxicity and identify potential targets for cardioprotection. Mice were intraperitoneally injected with 25 mg/kg CHK1 inhibitor AZD7762 and 20 mg/kg gemcitabine for 3 weeks. hiPSC-CMs and NMCMs were incubated with 0.5 uM AZD7762 and 0.1 uM gemcitabine for 24 h. Both pharmacological inhibition or genetic deletion of CHK1 and administration of gemcitabine induced mtROS overproduction and pyroptosis in cardiomyocytes by disrupting mitochondrial respiration, ultimately causing heart atrophy and cardiac dysfunction in mice. These toxic effects were further exacerbated with combination administration. Using mitochondria-targeting sequence-directed vectors to overexpress CHK1 in cardiomyocyte (CM) mitochondria, we identified the localization of CHK1 in CM mitochondria and its crucial role in maintaining mitochondrial redox homeostasis for the first time. Mitochondrial CHK1 function loss mediated the cardiotoxicity induced by AZD7762 and CHK1-knockout. Mechanistically, mitochondrial CHK1 directly phosphorylates SIRT3 and promotes its expression within mitochondria. On the contrary, both AZD7762 or CHK1-knockout and gemcitabine decreased mitochondrial SIRT3 abundance, thus resulting in respiration dysfunction. Further hiPSC-CMs and mice experiments demonstrated that SIRT3 overexpression maintained mitochondrial function while alleviating CM pyroptosis, and thereby improving mice cardiac function. In summary, our results suggest that targeting SIRT3 could represent a novel therapeutic approach for clinical prevention and treatment of cardiotoxicity induced by CHK1 inhibition and gemcitabine. [ABSTRACT FROM AUTHOR]

The application of DNA barcoding has been significantly limited by the scarcity of reliable specimens and inadequate coverage and replication across all species. The deficiency of DNA barcode reference coverage is particularly striking for highly biodiverse subtropical and tropical regions. In this study, we present a comprehensive barcode library for woody plants in tropical and subtropical China. Our dataset includes a standard barcode library comprising the four most widely used barcodes (rbcL, matK, ITS, and ITS2) for 2,520 species from 4,654 samples across 49 orders, 144 families, and 693 genera, along with 79 samples identified at the genus level. This dataset also provides a super-barcode library consisting of 1,239 samples from 1,139 species, 411 genera, 113 families, and 40 orders. This newly developed library will serve as a valuable resource for DNA barcoding research in tropical and subtropical China and bordering countries, enable more accurate species identification, and contribute to the conservation and management of tropical and subtropical forests. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor T cell (CAR-T) therapy stands as a precise and targeted approach in the treatment of malignancies. In this study, we investigated the feasibility of targeting Cadherin 17 (CDH17) with CDH17 CAR-T cells as a therapeutic modality for small cell lung cancer (SCLC). Methods: CDH17 expression levels were assessed in human SCLC tumor tissues and cell lines using qPCR and Western blot. Subsequently, we established CDH17 CAR-T cells and assessed their cytotoxicity by co-culturing them with various SCLC cell lines at different effector-to-target (E:T) ratios, complemented by ELISA assays. To ascertain the specificity of CDH17 CAR-T cells, we conducted experiments on SCLC cells with and without CDH17 expression (shRNAs). Furthermore, we employed an SCLC xenograft model to evaluate the in vivo efficacy of CDH17 CAR-T cells. Results: Our results revealed a significant upregulation of CDH17 in both SCLC tissues and cell lines. CDH17 CAR-T cells exhibited robust cytotoxic activity against SCLC cells in vitro, while demonstrating no cytotoxicity towards CDH17-deficient SCLC cells and HEK293 cells that lack CDH17 expression. Importantly, the production of IFN-γ and TNF-α by CDH17 CAR-T cells correlated with their cytotoxic potency. Additionally, treatment with CDH17 CAR-T cells significantly decelerated the growth rate of SCLC-derived xenograft tumors in vivo. Remarkably, no significant difference in body weight was observed between the control group and the group treated with CDH17 CAR-T cells. Conclusions: The preclinical data open further venues for the clinical use of CDH17 CAR-T cells as an immunotherapeutic strategy for SCLC treatment. [ABSTRACT FROM AUTHOR]

The great threat of microbes carried by ballast water calls for figuring out the species composition of the ballast-tank microbial community, where the dark, cold, and anoxic tank environment might select special taxa. In this study, we reconstructed 103 metagenome-assembled genomes (MAGs), including 102 bacteria and one archaea, from four vessels on international voyages. Of these MAGs, 60 were 'near complete' (completeness >90%), 34 were >80% complete, and nine were >75% complete. Phylogenomic analysis revealed that over 70% (n = 74) of these MAGs represented new taxa at different taxonomical levels, including one order, three families, 12 genera, and 58 species. The species composition of these MAGs was most consistent with the previous reports, with the most abundant phyla being Proteobacteria (n = 69), Bacteroidota (n = 17), and Actinobacteriota (n = 7). These draft genomes provided novel data on species diversity and function in the ballast-tank microbial community, which will facilitate ballast water and sediments management. [ABSTRACT FROM AUTHOR]

Through interface engineering and content control strategy, a PdBi bimetallic interface structure was constructed for the first time to selectively convert CO2 to formate with a remarkably high Faraday efficiency (FEformate) of 94% and a partial current density (jformate) of 34 mA·cm−2 at −0.8 V vs. reversible hydrogen electrode (RHE) in an H-cell. Moreover, the PdBi interface electrocatalyst even exhibited a high current density of 180 mA·cm−2 with formate selectivity up to 92% in a flow cell and could steadily operate for at least 20 h. Electrochemical in-situ attenuated total reflection surface enhanced infrared absorption spectroscopy (ATR-SEIRAS) confirmed that the PdBi interface could greatly weaken the adsorption of *CO intermediates due to electronic and geometric effects. Density functional theory (DFT) calculations also established that the PdBi interface regulated the CO2-to-formate pathway by reducing the energy barrier toward HCOOH and largely weakening the adsorption of *CO intermediates on the catalyst surface. This study reveals that the unique PdBi bimetallic interface can provide a novel platform to study the reaction mechanism through combining in-situ ATR-SEIRAS and DFT calculations. [ABSTRACT FROM AUTHOR]

Although genome-wide association studies (GWASs) have identified over 100 colorectal cancer (CRC) risk loci, an understanding of causal genes or risk variants and their biological functions in these loci remain unclear. Recently, genomic loci 10q26.12 with lead SNP rs1665650 was identified as an essential CRC risk loci of Asian populations. However, the functional mechanism of this region has not been fully clarified. Here, we applied an RNA interfering-based on-chip approach to screen for the genes essential for cell proliferation in the CRC risk loci 10q26.12. Notably, HSPA12A had the most significant effect among the identified genes and functioned as a crucial oncogene facilitating cell proliferation. Moreover, we conducted an integrative fine-mapping analysis to identify putative casual variants and further explored their association with CRC risk in a large-scale Chinese population consisting of 4054 cases and 4054 controls and also independently validated in 5208 cases and 20,832 controls from the UK biobank cohort. We identified a risk SNP rs7093835 in the intron of HSPA12A that was significantly associated with an increased risk of CRC (OR 1.23, 95% CI 1.08–1.41, P = 1.92 × 10–3). Mechanistically, the risk variant could facilitate an enhancer–promoter interaction mediated by the transcriptional factor (TF) GRHL1 and ultimately upregulate HSPA12A expression, which provides functional evidence to support our population findings. Collectively, our study reveals the important role of HSPA12A in CRC development and illustrates a novel enhancer–promoter interaction module between HSPA12A and its regulatory elements rs7093835, providing new insights into the etiology of CRC. [ABSTRACT FROM AUTHOR]

Load balancing is vital for the efficient and long-term operation of cloud data centers. With virtualization, post (reactive) migration of virtual machines (VMs) after allocation is the traditional way for load balancing and consolidation. However, it is not easy for reactive migration to obtain predefined load balance objectives and it may interrupt services and bring instability. Therefore, we provide a new approach, called Prepartition, for load balancing. It partitions a VM request into a few sub-requests sequentially with start time, end time and capacity demands, and treats each sub-request as a regular VM request. In this way, it can proactively set a bound for each VM request on each physical machine and makes the scheduler get ready before VM migration to obtain the predefined load balancing goal, which supports the resource allocation in a fine-grained manner. Simulations with real-world trace and synthetic data show that our proposed approach with offline version (PrepartitionOff) scheduling has 10%–20% better performance than the existing load balancing baselines under several metrics, including average utilization, imbalance degree, makespan and Capacity_makespan. We also extend Prepartition to online load balancing. Evaluation results show that our proposed approach also outperforms state-of-the-art online algorithms. [ABSTRACT FROM AUTHOR]

Highlights: Ultrathin P and Fe co-doped NiSe2 nanosheets supported on modified Ni foam are synthesized, which shows desirable bifunctional electrocatalytic hydrogen evolution reaction (HER)/hydrazine oxidation reaction (HzOR) performance in hydrazine-assisted water electrolysis and Zn-Hz battery. The coexistence of P and Fe heteroatoms induces an accelerated "2 + 2" reaction mechanism with a two-step HER process and a two-step HzOR step. Hydrazine-assisted water electrolysis is a promising energy conversion technology for highly efficient hydrogen production. Rational design of bifunctional electrocatalysts, which can simultaneously accelerate hydrogen evolution reaction (HER)/hydrazine oxidation reaction (HzOR) kinetics, is the key step. Herein, we demonstrate the development of ultrathin P/Fe co-doped NiSe2 nanosheets supported on modified Ni foam (P/Fe-NiSe2) synthesized through a facile electrodeposition process and subsequent heat treatment. Based on electrochemical measurements, characterizations, and density functional theory calculations, a favorable "2 + 2" reaction mechanism with a two-step HER process and a two-step HzOR step was fully proved and the specific effect of P doping on HzOR kinetics was investigated. P/Fe-NiSe2 thus yields an impressive electrocatalytic performance, delivering a high current density of 100 mA cm−2 with potentials of − 168 and 200 mV for HER and HzOR, respectively. Additionally, P/Fe-NiSe2 can work efficiently for hydrazine-assisted water electrolysis and Zn-Hydrazine (Zn-Hz) battery, making it promising for practical application. [ABSTRACT FROM AUTHOR]

The identification of additional Echinococcus granulosus sensu lato (s.l.) complex species/genotypes in recent years raises the possibility that there might be more variation among this species in China than is currently understood. The aim of this study was to explore intra- and inter-species variation and population structure of Echinococcus species isolated from sheep in three areas of Western China. Of the isolates, 317, 322, and 326 were successfully amplified and sequenced for cox1, nad1, and nad5 genes, respectively. BLAST analysis revealed that the majority of the isolates were E. granulosus s.s., and using the cox1, nad1, and nad5 genes, respectively, 17, 14, and 11 isolates corresponded to Elodea canadensis (genotype G6/G7). In the three study areas, G1 genotypes were the most prevalent. There were 233 mutation sites along with 129 parsimony informative sites. A transition/transversion ratio of 7.5, 8, and 3.25, respectively, for cox1, nad1, and nad5 genes was obtained. Every mitochondrial gene had intraspecific variations, which were represented in a star-like network with a major haplotype with observable mutations from other distant and minor haplotypes. The Tajima's D value was significantly negative in all populations, indicating a substantial divergence from neutrality and supporting the demographic expansion of E. granulosus s.s. in the study areas. The phylogeny inferred by the maximum likelihood (ML) method using nucleotide sequences of cox1–nad1–nad5 further confirmed their identity. The nodes assigned to the G1, G3, and G6 clades as well as the reference sequences utilized had maximal posterior probability values (1.00). In conclusion, our study confirms the existence of a significant major haplotype of E. granulosus s.s. where G1 is the predominant genotype causing of CE in both livestock and humans in China. [ABSTRACT FROM AUTHOR]

Genome-wide association studies have identified numerous variants associated with human complex traits, most of which reside in the non-coding regions, but biological mechanisms remain unclear. However, assigning function to the non-coding elements is still challenging. Here we apply Activity-by-Contact (ABC) model to evaluate enhancer-gene regulation effect by integrating multi-omics data and identified 544,849 connections across 20 cancer types. ABC model outperforms previous approaches in linking regulatory variants to target genes. Furthermore, we identify over 30,000 enhancer-gene connections in colorectal cancer (CRC) tissues. By integrating large-scale population cohorts (23,813 cases and 29,973 controls) and multipronged functional assays, we demonstrate an ABC regulatory variant rs4810856 associated with CRC risk (Odds Ratio = 1.11, 95%CI = 1.05–1.16, P = 4.02 × 10−5) by acting as an allele-specific enhancer to distally facilitate PREX1, CSE1L and STAU1 expression, which synergistically activate p-AKT signaling. Our study provides comprehensive regulation maps and illuminates a single variant regulating multiple genes, providing insights into cancer etiology.Here, the authors apply the Activity-by-Contact (ABC) model to infer enhancer-gene regulation and the effect of associated variants across multiple cancer types, integrating genetic and multi-omics data. Then, they explore the mechanisms associated with ABC regulatory variants in colorectal cancer. [ABSTRACT FROM AUTHOR]

To explore the relationship between physical exercise and smoking behavior among Chinese residents aged 16 years and older. Analysis based on 29,466 validated cases in the 2018 China Family Panel Studies (CFPS 2018). The chi-square test and Mann–Whitney U test were used for comparative analysis between groups. Logistic regression analysis was used to explore the relationship between physical exercise and smoking behavior. Gender and birth cohort differences in the relationship between physical exercise and smoking behavior were explored based on stratified regression analysis using gender and birth cohort as stratified variables, respectively. Robustness testing based on multiple linear regression analysis using a replacement data approach. There were 8735 cases of smokers among the respondents. After controlling for relevant confounders, there was a significant negative association between physical exercise and smoking behavior among residents [OR 0.718, 95% CI (0.673, 0.765), P < 0.01]. Physical exercise was more significantly associated with smoking behavior among male residents [OR 0.694, 95% CI (0.649, 0.743), P < 0.01], while it was not significantly associated with smoking behavior among female residents [OR 0.901, 95% CI (0.743, 1.093), P > 0.05]. Physical exercise was more significantly associated with smoking behavior in the pre-1948 (OR 0.748), 1959–1968 (OR 0.748), 1969–1978 (OR 0.812), 1989–1998 (OR 0.576) and post-1999 (OR 0.411) birth cohorts, and the association decreased over time and with social change. The results of the robustness test showed that frequency of exercise was significantly and negatively associated with smoking behavior among residents [OR 0.961, 95% CI (0.951, 0.970), P < 0.01]. Physical exercise is negatively associated with smoking behavior among Chinese residents aged 16 years and older, especially among male residents. There is a cohort effect between physical exercise and smoking behavior of the population, that is, the relationship between the two decreases with social change. [ABSTRACT FROM AUTHOR]

Symbiotic microbiomes of Sphagnum have been confirmed to play a fundamental role in carbon and nitrogen cycles, however, little is known about microbiomes associated with other bryophytes in subtropical peatland ecosystems. To explore the differences in community structure, metabolic potential and interaction relationship of bacterial microbiomes associated with different bryophytes species, the gametophytes of three bryophyte species (Sphagnum palustre, Aulacomnium androgynum, and Polytrichum commune) and their underlying peat sediments were collected from the subtropical Dajiuhu Peatland and subjected to Illumina high-throughout sequencing of 16S rRNA gene. Results showed that bacterial diversity was lowest in S. palustre, the dominant moss species, among the three moss species investigated in Dajiuhu Peatland. Bacterial communities from bryophytes clearly separated with those from sediments as indicated by both phylogenetic and taxonomical approaches. Linear discriminant analysis effect size (LEfSe) identified 30 and 36 indicator taxa in mosses and peat sediments. Bacteroidetes, Verrucomicrobia and Thermoleophilia significantly enriched in S. palustre, A. androgynum and P. commune, Chloroflexi, Proteobacteria and Acidobacteria subgroup 6 was indicator taxa for corresponding underlying sediments, respectively. Despite of these differences in compositions, bacterial functional structures were similar among all bryophytes, such as abundant aerobic heterotrophs, rare nitrifiers and denitrifiers. This phenomenon was also observed among the underlying sediments. Network analysis indicated that Proteobacteria and Acidobacteria located in the center of network and exerted strong interactions to other taxa. The sub-network of bacterial communities in sediments was more connected and microbial groups were more competitive than those in bryophytes subnetwork. Our results offer new insight into the community structure, ecological function and interaction pattern of bacterial microbiomes in the Dajiuhu Peatland across different habitats. [ABSTRACT FROM AUTHOR]

Introduction: Inflammation is a defensive response of the organism to irritation which is manifested by redness, swelling, heat, pain and dysfunction. The inflammatory response underlies the role of various diseases. Ferroptosis, a unique modality of cell death, driven by iron-dependent lipid peroxidation, is regulated by multifarious cellular metabolic pathways, including redox homeostasis, iron processing and metabolism of lipids, as well as various signaling pathways associated with diseases. A growing body of evidence suggests that ferroptosis is involved in inflammatory response, and targeting ferroptosis has great prospects in preventing and treating inflammatory diseases. Materials and methods: Relevant literatures on ferroptosis, inflammation, inflammatory factors and inflammatory diseases published from January 1, 2010 to now were searched in PubMed database. Conclusion: In this review, we summarize the regulatory mechanisms associated with ferroptosis, discuss the interaction between ferroptosis and inflammation, the role of mitochondria in inflammatory ferroptosis, and the role of targeting ferroptosis in inflammatory diseases. As more and more studies have confirmed the relationship between ferroptosis and inflammation in a wide range of organ damage and degeneration, drug induction and inhibition of ferroptosis has great potential in the treatment of immune and inflammatory diseases. [ABSTRACT FROM AUTHOR]

In the "treat all" era, the high rate of late HIV diagnosis (LHD) worldwide remains an impediment to ending the HIV epidemic. In this study, we analyzed LHD in newly diagnosed people living with HIV (PLWH) and its impact on HIV transmission in Northeast China. Sociodemographic information, baseline clinical data, and plasma samples obtained from all newly diagnosed PLWH in Shenyang, the largest city in Northeast China, between 2016 and 2019 were evaluated. Multivariate logistic regression analysis was performed to identify risk factors associated with LHD. A molecular network based on the HIV pol gene was constructed to assess the risk of HIV transmission with LHD. A total of 2882 PLWH, including 882 (30.6%) patients with LHD and 1390 (48.2%) patients with non-LHD, were enrolled. The risk factors for LHD were older age (≥ 30 years: p <.01) and diagnosis in the general population through physical examination (p <.0001). Moreover, the molecular network analysis revealed that the clustering rate (p <.0001), the fraction of individuals with ≥ 4 links (p =.0847), and the fraction of individuals linked to recent HIV infection (p <.0001) for LHD were significantly or marginally significantly lower than those recorded for non-LHD. Our study indicates the major risk factors associated with LHD in Shenyang and their limited contribution to HIV transmission, revealing that the peak of HIV transmission of LHD at diagnosis may have been missed. Early detection, diagnosis, and timely intervention for LHD may prevent HIV transmission. [ABSTRACT FROM AUTHOR]

Bathyarchaeota are believed to have roles in the carbon cycle in marine systems. However, the ecological knowledge of Bathyarchaeota is limited in peatland ecosystems. Here, we investigated the vertical distribution of Bathyarchaeota community structure using quantitative PCR and high-throughput sequencing technology of ribosomal 16S rRNA gene integrated with detailed chemical profiling in the Dajiuhu Peatland, central China. Eight archaeal phyla were observed in peat samples, which mainly composed of Bathyarchaeota with a mean relative abundance about 88%, followed by Thaumarchaeota (9%). Bathyarchaeota were further split into 17 subgroups, and some subgroups showed habitat specificity to peat horizons with distinct lithological and physicochemical properties, for example, Bathy-6 and Bathy-15 had preference for the acrotelm, Bathy-5b, Bathy-16, and Bathy-19 were enriched in the catotelm, Bathy-5a, Bathy-8, and Bathy-11 were specific for the clay horizon. This spatial distribution pattern of archaeal communities along peat profile was mainly influenced by water content as indicated by RDA ordination and permutational MANOVA, whereas organic matter content exclusively affected Bathyarchaeota distribution along the peat profile significantly. The abundance of archaeal 16S rRNA genes ranged from 105 to 107 copies per gram dry sediment, and the highest archaeal biomass was observed in the periodically oxic mesotelm horizon with more dynamic archaeal interaction relationship as indicated by the network analysis. Bathyarchaeota dominated the archaeal interaction network with 82% nodes, 96% edges, and 71% keystone species. Our results provide an overview of the archaeal population, community structure, and relationship with environmental factors that affect the vertical distribution of archaeal communities and emphasize the ecology of bathyarchaeotal lineages in terrestrial peatland ecosystems. [ABSTRACT FROM AUTHOR]

Purpose: The prognostication for the injured recurrent laryngeal nerve (RLN) with incomplete loss of signal (LOS) and its function outcome have not been well unified. A warning criterion was proposed to predict RLN injury during monitored thyroidectomy. Methods: A retrospective review of prospectively collected data from consecutive 357 patients with 560 nerves at risk was conducted. Vocal cords mobility with laryngoscope was performed preoperatively, on the second day, and once a month postoperatively until complete recovery. Different cutoff values of the percentage reduction in sum of the amplitude of left and right channel at the end of the surgery, for postoperative vocal cord paralysis (VCP) prediction were compared. Results: Percentage reduction in sum of the amplitude of left and right channel at the end of operation ranged from 30.2 to 63.6% in 27 nerves with incomplete LOS (absolute amplitude value of final R2 > 100 μV with reduction > 50% of R1). Seven (1.25%) nerves experienced transient postoperative VCP, in which one nerve with postoperative VCP showed no amplitude reduction. The positive predictive value of VCP for the sum amplitude reduction exceeding 30, 40, 50, and 60% was 22.2, 40, 85.7, and 100%, respectively. Accuracy was 96.1, 98.2, 99.6, 99.4%, respectively. Conclusion: Percentage reduction in sum of the amplitude of left and right channel is a meaningful method to improve the accuracy of VCP prediction. When the sum amplitude reduction ≥ 50%, surgeons should consider the possibility of postoperative VCP and correct some surgical maneuvers. [ABSTRACT FROM AUTHOR]

Parasitic infection is one of the many challenges facing livestock production globally. Cysticercosis tenuicollis is a common parasitic disease in domestic and wild ruminants (intermediate host) caused by the larval stage of Taenia hydatigena that primarily infects dogs (definitive host). Although genetic studies on this parasite exist, only a few describe the genetic variation of this parasite in Mongolia. Our aim was thus, to identify the mitochondrial differences in ovine isolates of Cysticercus tenuicollis entering China from Mongolia and comparison with existing Chinese isolates from sheep and goats based on the recently described PCR–RFLP method and mitochondrial genes of NADH dehydrogenase subunit 4 (nad4) and the NADH dehydrogenase subunit 5 (nad5). Sixty-nine isolates were collected during routine veterinary meat inspections from sheep that originated from Mongolia, at the modern slaughterhouses in Erenhot City, Inner Mongolia. Additional 114 cysticerci were also retrieved from sheep and goats from northern (Inner Mongolia Autonomous Region, Ningxia Hui Autonomous Region, and Gansu Province), western (Tibet Autonomous Region), and southern (Jiangxi Province and Guangxi Province) China. The PCR–RFLP approach of the nad5 showed nine mitochondrial subclusters A1, A2, A3, A5, A8, A9, A10, A11, and B of T. hydatigena isolates from sheep and goats from Mongolia and China. Meanwhile, haplogroup A1 RFLP profile was more widespread than other variants. These data supplements existing information on the molecular epidemiology of T. hydatigena in China and Mongolia and demonstrate the occurrence of similar genetic population structures in both countries. [ABSTRACT FROM AUTHOR]

Intracellular Ca2+ dysregulation is a key marker in septic cardiac dysfunction; however, regulation of the classic Ca2+ regulatory modules cannot successfully abolish this symptom. Here we show that the knockout of transient receptor potential canonical (TRPC) channel isoforms TRPC1 and TRPC6 can ameliorate LPS-challenged heart failure and prolong survival in mice. The LPS-triggered Ca2+ release from the endoplasmic reticulum both in cardiomyocytes and macrophages is significantly inhibited by Trpc1 or Trpc6 knockout. Meanwhile, TRPC's molecular partner — calmodulin — is uncoupled during Trpc1 or Trpc6 deficiency and binds to TLR4's Pococurante site and atypical isoleucine-glutamine-like motif to block the inflammation cascade. Blocking the C-terminal CaM/IP3R binding domain in TRPC with chemical inhibitor could obstruct the Ca2+ leak and TLR4-mediated inflammation burst, demonstrating a cardioprotective effect in endotoxemia and polymicrobial sepsis. Our findings provide insight into the pathogenesis of endotoxemic cardiac dysfunction and suggest a novel approach for its treatment. TRPCs, nonselective cation channels, are involved in cardiac contraction and conduction. Here, the authors show that Trpc1/6 deficiency or pharmacological inhibition improves endotoxemic cardiac dysfunction and prolongs survival by prominently suppressing cardiac inflammation and ER Ca2+ release. [ABSTRACT FROM AUTHOR]

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As an effective tool for data analysis, formal concept analysis (FCA) is widely used in software engineering and machine learning. The construction of concept lattice is a key step of the FCA. How to effectively to update the concept lattice is still an open, interesting and important issue. To resolve this problem, an incremental algorithm for concept lattice on image structure similarity (SsimAddExten) was presented. The proposed method mapped each knowledge class on the conceptlattice into a graphic, when a new object was added or deleted in a knowledge class, the boundary profile of graphic will be changed, the graphic edge structure similarity was introduced as the calculation index of the change degree before and after the knowledge, and the concept lattice will be updated on the basis of the index. We performed experiments to test SsimAddExtent, whose computational efficiency obtains obvious advantages over mainstream methods on almost all test points, especially on the data set with a large number of attributes. But, its complexity is not reduced compared with mainstream methods. Both theoretical analysis and performance test show SsimAddExtent algorithm is better choice when we apply the FCA to large scale data or non-sparse data. [ABSTRACT FROM AUTHOR]

The understanding of the mechanical behavior of granite containing fissures is of great significance for geothermal energy exploitation and high-level nuclear waste disposal repository. To consider the grain interlocking and rotational resistance behavior in granite specimens, the grain-based model 3D (GBM3D) was constructed to investigate the fracture behavior of granite specimens containing a single fissure. The numerical result indicates that this GBM3D can be used to investigate the mechanical behavior of granite constituted by different minerals, and it can provide more information to understand the mechanical behavior of specimens under loading process. The inter-granular cracks initiate in the first place, but the initiation of intra-granular cracks mainly concentrates after the peak strength. The tensile cracks between different minerals are more than that between the same minerals, and the intra-granular cracks in muscovite initiate firstly, and the number of them is more than that in other minerals. The wing crack is mainly constituted by the inter-granular cracks, and the shape of it is different in different depths, whereas the anti-wing is similar in different depths. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles (EVs) contain thousands of proteins and nucleic acids, playing an important role in cell–cell communications. Sertoli cells have been essential in the testis as a "nurse cell". However, EVs derived from human Sertoli cells (HSerCs) have not been well investigated. Methods: EVs were isolated from HSerCs via ultracentrifugation and characterized by transmission electron microscopy, tunable resistive pulse sensing, and Western blotting. The cargo carried by HSerCs-EVs was measured via liquid chromatography-mass spectrometry and GeneChip miRNA Arrays. Bioinformatic analysis was performed to reveal potential functions of HSerCs-EVs. Results: A total of 860 proteins with no less than 2 unique peptides and 88 microRNAs with high signal values were identified in HSerCs-EVs. Biological processes related to molecular binding, enzyme activity, and regulation of cell cycle were significantly enriched. Specifically, many proteins in HSerCs-EVs were associated with spermatogenesis and regulation of immune system, including Septins, Large proline-rich protein BAG6, Clusterin, and Galectin-1. Moreover, abundant microRNAs within HSerCs-EVs (miR-638, miR-149-3p, miR-1246, etc.) had a possible impact on male reproductive disorders such as asthenozoospermia and oligozoospermia. Conclusions: Our study has shown that HSerCs-EVs contain diverse components such as proteins and microRNAs. Further research is required to evaluate HSerCs-EVs in spermatogenesis, which are underutilized but highly potent resources with particular promise for male infertility. [ABSTRACT FROM AUTHOR]

The aim of this paper is to develop 10-year cardiovascular disease (CVD) risk prediction models for the contemporary Chinese populations based on the Guangzhou Biobank Cohort Study (GBCS) and to compare its performance with models based on Framingham's general cardiovascular risk profile and the Prediction for Atherosclerotic CVD Risk in China (China-PAR) project. Subjects were randomly classified into the training (n = 15,000) and validation (n = 12,721) sets. During an average of 12.0 years' follow-up, 3,732 CVD events occurred. A 10-year sex-specific CVD risk prediction model including age, systolic blood pressure, use of antihypertensive medication, smoking, and diabetes was developed. Compared with the Framingham and China-PAR models, the GBCS model had a better discrimination in both women (c-statistic 0.72, 95% CI 0.71–0.73) and men (c-statistic 0.68, 95% CI 0.67–0.70), and the risk predicted was closer to the actual risk. This prediction model would be useful for identifying individuals at higher risks of CVD in contemporary Chinese populations. [ABSTRACT FROM AUTHOR]

Segmental overgrowth of the skeletal muscles with bone involvement in body extremities, predominantly affecting the upper limb, is an extremely rare condition with only 40–50 affected children described clinically. The molecular pathogenesis of this disorder remains largely unclear except for the identification of a somatic PIK3CA mutation in each of the six patients genetically tested, all restricted to upper limbs in the literature. This study aimed to further characterize the molecular defects for patients affected with segmental overgrowth of the skeletal muscles by analyzing a 9-gene panel selected from the PI3K/AKT/mTOR pathway and genes associated with other related conditions. Nineteen unrelated patients were chosen for this study, comprising ten upper limb (nine unilateral and one bilateral) and nine lower limb (eight unilateral and one bilateral) cases with variable bone involvement. In each case, an activating PIK3CA mutation (p.E110del, p.N345K, p.E542K, p.E545K, p.H1047R, or p.H1047L) was identified in the affected muscle tissue with variant allele frequencies ranging from 13.88 to 30.43%, while no mutation was detected in the paired peripheral blood sample, indicating somatic mosaicism. All detected mutations were limited to PIK3CA and were previously reported in other overgrowth syndromes currently categorized under the PIK3CA-Related Overgrowth Spectrum (PROS). Our study provides strong molecular evidence that isolated segmental overgrowth of the skeletal muscle with bone involvement is a subtype of PROS. Our findings expand the PROS clinical presentations with a newly molecularly classified condition and can provide guidance in clinical and molecular diagnosis and treatment for patients with this condition. [ABSTRACT FROM AUTHOR]

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In this work, we determine up/down-quark mass m q = u / d in the isoscalar scalar channel from both the Shifman–Vainshtein–Zakharov (SVZ) and the Monte-Carlo-based QCD sum rules. The relevant spectral function, including the contributions from the f 0 (500) , f 0 (980) and f 0 (1370) resonances, is determined from a sophisticated U(3) chiral study. Via the traditional SVZ QCD sum rules, we give the prediction to the average light-quark mass m q (2 GeV) = 1 2 (m u (2 GeV) + m d (2 GeV)) = (3. 46 - 0.22 + 0.16 ± 0.33) MeV . Meanwhile, by considering the uncertainties of the input QCD parameters and the spectral functions of the isoscalar scalar channel, we obtain m q (2 GeV) = (3.44 ± 0.14 ± 0.32) MeV from the Monte-Carlo-based QCD sum rules. Both results are perfectly consistent with each other, and nicely agree with the Particle Data Group value within the uncertainties. [ABSTRACT FROM AUTHOR]

The security of cyber-physical systems (CPS) has become an active research area in recent years. Autonomous micro-grid, an important component of smart grid and essentially a cyber-physical system, extends the attack surface and undermines system security. This paper proposes a game-theoretic approach to describe the plausible attack-defense dynamics for autonomous micro-grid. The game is a kind of two-player, one shot, non-cooperative, and Zero-sum game, where the goal of attackers in this game is to gain the maximum payoff under a certain cost. The behavior of attackers includes two steps, intrusion and disruption, whereas the defenders can improve their defense performance by updation or reinforcement of cyber component. The optimal strategy of attackers is deduced based on the dynamic model. Finally, the case studies validate the proposed method and demonstrate its feasibility. [ABSTRACT FROM AUTHOR]

A new grain-based model (NGBM) was presented based on the cluster logic to vividly mimic the granitic basement rock. This model introduced a lower strength at the intra-granular and the zigzag of the grain boundary, and then it was used to simulate the Bukit Timah granite under tensile and compression. The non-linear strength with confining pressure, failure mode, and shear bands was investigated and compared with GBM. The results show that the NGBM can better simulate the failure modes and non-linear characteristic of peak strength with confining pressure, especially under higher confining pressure. Particularly, NGBM can better mimic the crack evolution process under direct tension and triaxial compression compared with GBM. It is also found that the crack evolution process can be divided into the typical three stages, which are similar to experimental observations. The shear bands simulated by NGBM are closer to experimental ones than those by GBM. [ABSTRACT FROM AUTHOR]

Canonical transient receptor potential channels (TRPCs) are nonselective, high calcium permeability cationic channels. The TRPCs family includes TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7. These channels are widely expressed in the cardiovascular and nervous systems and exist in many other human tissues and cell types, playing several crucial roles in the human physiological and pathological processes. Hence, the emergence of TRPCs modulators can help investigate these channels' applications in health and disease. It is worth noting that the TRPCs subfamilies have structural and functional similarities, which presents a significant difficulty in screening and discovering of TRPCs modulators. In the past few years, only a limited number of selective modulators of TRPCs were detected; thus, additional research on more potent and more selective TRPCs modulators is needed. The present review focuses on the striking desired therapeutic effects of TRPCs modulators, which provides intel on the structural modification of TRPCs modulators and further pharmacological research. Importantly, TRPCs modulators can significantly facilitate future studies of TRPCs and TRPCs related diseases. [ABSTRACT FROM AUTHOR]

Purpose: Ultrasomics is a radiomics technique that extracts high-throughput quantitative data from ultrasound imaging. The aim of this study was to differentiate malignant from benign focal liver lesions (FLLs) using two-dimensional shear wave elastography (2D-SWE)-based ultrasomics. Methods: A total of 175 FLLs in 169 patients were prospectively analyzed. The study population was divided into a training cohort (n = 122) and a validation cohort (n = 53). The maxima, minima, mean, and standard deviation of 2D-SWE measurements were expressed in kilopascals (Emax, Emin, Emean, and ESD). The ultrasonics technique was used to extract the features from the 2D-SWE images. Support vector machine was used to establish two prediction models: the ultrasomics score (ultrasomics features only) and the combined score (SWE measurements and ultrasomics features). The diagnostic performance of the models in differentiating FLLs was analyzed. Results: A total of 1044 features were extracted and 15 features were selected. The AUC for the combined score, ultrasomics score, Emax, Emean, Emin and ESD were 0.94, 0.91, 0.92, 0.89, 0.67, and 0.89, respectively. The combined score had the best diagnostic performance. The sensitivity, specificity, PPV, NPV, +LR, LR of the combined score were 92.59%, 87.50%, 94.59%, 82.50%, 7.35%, and 0.09%, respectively. The decision curve analysis results showed that when the threshold probability was > 29%, the combined score showed improved benefits for patients compared to using the ultrasomics score and 2D-SWE measurements. Conclusion: The results of this study demonstrated that the combined score had good diagnostic accuracy in differentiating malignant from benign FLLs. [ABSTRACT FROM AUTHOR]

In this study, a new adaptive morphological filter is developed based on the mathematical morphology algorithm and characteristics of the subtle differences in the waveform morphology in seismic data. The algorithm improves the traditional morphological dilation and corrosion operations. In this study, we propose a multiscale adaptive operator based on the principle of morphological structural "probes" and present the corresponding mathematical proof. Simulation experiments and actual seismic data processing results show that compared with traditional morphological filters, the constructed OCCO-based multistructure adaptive morphological filter can suppress noise to the greatest extent. Moreover, it can effectively improve the SNR of the images, and offers great application prospects. [ABSTRACT FROM AUTHOR]

Granite is a viable host for deep nuclear waste disposal because its low permeability and high strength enable the stable and safe operation of the repository. We examined the evolution of the permeability and triaxial mechanical behaviour of granite after high-temperature treatment. First, the effect of the high temperature on the physical behaviour and permeability evolution of granite was analysed in detail. The mass, P-wave velocity, and thermal conductivity of granite decrease, but the volume increases with increasing temperature. The permeability of intact granite increases by four orders of magnitude as the cycled temperature increases from 25 to 800 °C. Subsequently, the effect of high temperature on the triaxial deformation and acoustic emission (AE) behaviour of granite was investigated. Under uniaxial compression at T ≤ 300 °C, the stress decreases before the peak strength is reached, corresponding to a significant AE event, which is due to the development of multiple splitting tensile fractures along the loading direction. At T ≥ 450 °C, AE event is observed once a minor stress is applied, which results from failure is controlled by thermally induced cracks. However, under triaxial compression, the temperature has little effect on the AE characteristics. The granite fails along the shear fracture plane, which becomes wider with increasing confining pressure. At T ≥ 600 °C, it is easier to form intragranular cracks and the stress quickly decreases after the peak strength is reached. The shear plane is smoother under high confining pressure. Third, the effect of high temperature on the peak strength and crack damage threshold of granite was further analysed. Generally, under uniaxial compression, the peak strength and crack damage threshold first remain relatively constant at T ≤ 300 °C, begin to decrease at T = 450 °C, and decrease more rapidly at T = 600 °C. The confining pressure notably reduces the effect of the temperature on the peak strength and crack damage threshold. Finally, the effect and mechanism of high temperature on the triaxial strength parameters of granite were further discussed. At T ≤ 300 °C, thermally induced cracks are not notable and the temperature has little effect on the strength. At 450 °C≤ T ≤ 600 °C, thermally induced cracks are more notable and the temperature has a significant effect on the strength behaviour. Because of the thermal stress released by thermal macrocrack formation, the continuous increase in the temperature has little impact on strength. [ABSTRACT FROM AUTHOR]

To understand the fracture coalescence in specimens containing oval flaws, PFC2D was used to investigate the sandstone containing two oval flaws with different ligament angles under uniaxial compression. The micro-parameters were first confirmed by intact sandstone, and then, these were adopted to simulate the flawed specimen under uniaxial compression. Numerical results show that the peak strength, the peak strain, elastic modulus, and the ultimate failure modes were approximated well with these obtained by experiment. The failure modes obtained by numerical simulation can be divided into the following four typical categories based on the crack coalescence between the pre-existing flaws: no crack coalescence; indirect crack coalescence outside the bridge area; single crack coalescence inside the bridge area; tensile crack coalescence outside the bridge area. Based on parallel bond force fields and stress variation of measurement circles along the crack trajectory, the crack evolution processes were analyzed in detail and crack types were identified. The mode III can be divided into mode IIIa and mode IIIb. The mode IIIa is the single shear crack coalesced inside the bridge area; the mode IIIb is the single crack that initiated with tensile crack and coalesced with shear crack, and it only occurred as β = 90°. The mode IV can be divided into mode IVa and mode IVb. The mode IVa is that wing crack initiated at the middle of oval and coalesced at another oval tip, and it occurred as β = 120°. The mode IVb is that coalesced with anti-wing crack outside the bridge area, and it occurred as β = 150°. The stress distribution along the ligament has an obvious effect on ligament angle and flaw angle, and crack initiation only affects the stress concentration factor value. [ABSTRACT FROM AUTHOR]

Background: Despite the fact that thyroid surgery has evolved towards minimal incisions and endoscopic approaches, the role of total endoscopic thyroidectomy (TET) in thyroid cancer has been highly disputed. We performed a systematic review and meta-analyses of peer reviewed studies in order to evaluate the safety and effectiveness of TET compared with conventional open thyroidectomy (COT) in papillary thyroid cancer (PTC).Method: Medical literature databases such as PubMed, Embase, the Cochrane Library, and Web of science were systematically searched for articles that compared TET and COT in PTC treatment from database inception until March 2019. The quality of the studies included in the review was evaluated using the Downs and Black scale using Review Manager software Stata V.13.0 for the meta-analysis.Results: The systematic review and meta-analysis were based on 5664 cases selected from twenty publications. Criteria used to determine surgical completeness included postoperative thyroglobulin (TG) levels, recurrence of the tumor after long-term follow-up. Adverse event and complication rate scores included transient recurrent laryngeal nerve (RLN) palsy, permanent RLN palsy, transient hypocalcaemia, permanent hypocalcaemia, operative time, number of removed lymph nodes, length of hospital stay and patient cosmetic satisfaction. TET was found to be generally equivalent to COT in terms of surgical completeness and adverse event rate, although TET resulted in lower levels of transient hypocalcemia (OR 1.66; p < 0.05), a smaller number of the retrieved lymph nodes (WMD 0.46; p < 0.05), and better cosmetic satisfaction (WMD 1.73; p < 0.05). COT was associated with a shorter operation time (WMD - 50.28; p < 0.05) and lower rates of transient RLN palsy (OR 0.41; p < 0.05).Conclusions: The results show that in terms of safety and efficacy, TET was similar to COT for the treatment of thyroid cancer. Indeed, the tumor recurrence rates and the level of surgical completeness in TET are similar to those obtained for COT. TET was associated with significantly lower levels of transient hypocalcemia and better cosmetic satisfaction, and thus is the better option for patients with cosmetic concerns. Overall, randomized clinical trials and studies with larger patient cohorts and long-term follow-up data are required to further demonstrate the value of the TET. [ABSTRACT FROM AUTHOR]