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Gradation of Disability in Human Body Injuries （hereinafter referred to as Gradation） has been released and used since January 2017, and has become the most widely used standard in forensic science practice. This paper calculates and rates the visual system evaluation provisions of the current domestic disability evaluation criteria represented by the Gradation which used the methods of Guides to the Evaluation of Permanent Impairment （hereinafter referred to as GEPI） issued by American Medical Association （AMA）. Through comparing, a good correlation between the provisions in Gradation and whole person impairment rating index in GEPI was shown. On the basis of this, suggestions are put forward to amend some provisions of Gradation, in order to provide reference for the revision and further improvement of domestic standards and provisions.

Functional and structural disturbances in the orbitofrontal–striatal–thalamic circuitry are thought to be associated with mental symptoms and neurocognitive impairments in schizophrenia. This study tested whether synapse-associated protein 97 (SAP97), a reasonable candidate gene for schizophrenia, is related to orbitofrontal–striatal–thalamic connection changes in first-episode schizophrenia (FES) patients and the clinical performance of schizophrenic patients by affecting this integrity. Fifty-two FES patients and 52 matched healthy controls were recruited. All subjects underwent genotyping via the improved multiplex ligation detection reaction technique and scanning with magnetic resonance imaging (MRI) to provide orbitofrontal–striatal–thalamic functional and structural imaging data. A two-way analysis of covariance model was employed to examine abnormal brain connectivities, and Spearman correlations were applied to estimate the relationships between brain connectivity and clinical manifestations. In the FES group, those with the SAP97 rs3915512 TT genotype showed lower structural and functional connectivity than A allele carriers between the orbitofrontal gyrus and striatum/thalamus. In the FES group, negative correlations were found between resting-state functional connectivity (RSFC) in the orbitofrontal gyrus and thalamus, and positive symptoms between structural connections in the orbitofrontal gyrus and striatum and cognitive functions, and positive correlations were suggested between RSFC in the orbitofrontal gyrus and thalamus and negative symptoms. Our findings suggested that the SAP97 rs3915512 polymorphism may be involved in mental symptoms and cognitive dysfunction in FES patients by influencing structural and functional connectivity of the orbitofrontal–striatal and orbitofrontal–thalamic regions.

Objective: Our group aimed to investigate the expression pattern of miRNA-873-5p in cervical cancer (CC) patients and its association with CC progression. Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied for the examination of the expressions of miRNA-873-5p in both CC specimens and cell lines. The clinical significance of miRNA-873-5p was statistically analyzed. MTT, colony formation, Transwell and flow cytometry assays were used to detect cell proliferation, metastasis, and apoptosis changes of Hela and Siha cell line. Luciferase reporter assays and Western blots were utilized to identify the target genes of miRNA-873-5p. Western blot and RT-PCR were used to judge the dysregulation of Notch signaling. Results: Our results indicated that miRNA-873-5p expression was distinctly reduced in CC patients. Low miRNA-873-5p expressions were distinctly correlated with positively distant metastasis, The International Federation of Gynecology and Obstetrics (FIGO) stage and poor prognosis of CC patients. A functional assay using miRNA-873-5p mimics indicated that overexpression of miRNA-873-5p distinctly suppressed CC cells proliferation and metastasis, and promoted apoptosis. Bioinformatic assays revealed that miRNA-873-5p may target the 3’-UTR of ZEB1 and lead to the suppression of its translation, which was verified by the use of luciferase assays. Finally, overexpression of miRNA-873-5p suppressed the expressions of Jag1, Maml2 and Hey1. Conclusion: Taken together, we firstly provided evidence that miRNA-873-5p expression was a poor favorable factor for CC patients, and the use of miRNA-873-5p may represent a and potential biomarker and promising therapeutic approach for CC.

BackgroundProteins containing the caspase recruitment domain (CARD) play critical roles in cell apoptosis and immunity. However, the impact of CARD genes in tumor immune cell infiltration, responsiveness to checkpoint immunotherapy, and clinical outcomes of gliomas remains unclear. Here, we explore using CARD genes to depict the immune microenvironment and predict the responsiveness of gliomas to anti-PD-1 therapy.MethodsThe genome and transcriptome data of 231 patients with isocitrate dehydrogenase wild-type (IDH-wt) gliomas were retrieved from The Cancer Genome Atlas (TCGA) database to screen CARD genes associated with T lymphocyte infiltration in gliomas. Weighted co-expression network and LASSO penalized regression were employed to generate a CARD-associated risk score (CARS). Two independent and publicly available datasets were used to validate the effectiveness of CARS.ResultsThe CARS divided the 231 glioma patients into high- and low-risk subgroups with distinct immune microenvironment and molecular features. The high-risk group had high CARS and was characterized by enrichment of dysfunctional T lymphocytes in a profound immunosuppressive microenvironment, whereas the low-risk group had low CARS and exhibited an immune exclusion genotype. Moreover, signaling aberrations including upregulation of PI3K/Akt/mTOR, NF-κB, and TGF-β were found in the high-risk group. In contrast, the activated WNT pathway was more evident in the low-risk group. Furthermore, we found that an elevated CARS indicated a decreased overall survival for IDH-wt gliomas under standard care but a clinical benefit from checkpoint immunotherapy.ConclusionThis study developed an immune- and prognosis-relevant risk score, which could be used to enhance our understanding of the heterogeneity of immune microenvironment of gliomas and facilitate to identify patients who will benefit from checkpoint immunotherapy.

Posttranslational modifications, such as SUMOylation, play specific roles in the life cycle of invading pathogens. However, the effect of SUMOylation on the adaptation, pathogenesis, and transmission of influenza A virus (IAV) remains largely unknown. Here, we found that a conserved lysine residue at position 612 (K612) of the polymerase basic protein 1 (PB1) of IAV is a bona fide SUMOylation site. SUMOylation of PB1 at K612 had no effect on the stability or cellular localization of PB1, but was critical for viral ribonucleoprotein (vRNP) complex activity and virus replication in vitro. When tested in vivo, we found that the virulence of SUMOylation-defective PB1/K612R mutant IAVs was highly attenuated in mice. Moreover, the airborne transmission of a 2009 pandemic H1N1 PB1/K612R mutant virus was impaired in ferrets, resulting in reversion to wild-type PB1 K612. Mechanistically, SUMOylation at K612 was essential for PB1 to act as the enzymatic core of the viral polymerase by preserving its ability to bind viral RNA. Our study reveals an essential role for PB1 K612 SUMOylation in the pathogenesis and transmission of IAVs, which can be targeted for the design of anti-influenza therapies.

Objective: To investigate the effects of microRNA-137 (MIR137) polymorphisms (rs1198588 and rs2660304) on the risk of schizophrenia in a Han Chinese population.Methods: Schizophrenia was diagnosed according to the DSM-5. Clinical symptoms and cognitive functions were assessed with the Positive and Negative Symptom Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS), respectively. The polymorphisms were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 1,116 patients with schizophrenia and 1,039 healthy controls.Results: Significant associations were found between schizophrenia and MIR137 in the distributions of genotypes (p = 0.037 for rs1198588; p = 0.037 for rs2660304, FDR corrected) and alleles (p = 0.043 for rs1198588; p = 0.043 for rs2660304, FDR corrected) of two SNPs. When the population was stratified by sex, we found female-specific associations between MIR137 and schizophrenia in terms of genotype and allele distributions of rs1198588 (χ2 = 4.41, p = 0.036 and χ2 = 4.86, p = 0.029, respectively, FDR corrected) and rs2660304 (χ2 = 4.74, p=0.036 and χ2 = 4.80, p = 0.029, respectively, FDR corrected). Analysis of the MIR137 haplotype rs1198588-rs2660304 showed a significant association with schizophrenia in haplotype T-T [χ2 = 4.60, p = 0.032, OR = 1.32, 95% CI (1.02–1.70)]. Then, significant female-specific associations were found with the haplotypes T-T and G-A [χ2 = 4.92, p = 0.027, OR = 1.62, 95% CI (1.05–2.50); χ2 = 4.42, p = 0.035, OR = 0.62, 95% CI (0.39–0.97), respectively]. When the TT genotype of rs1198588 was compared to the GT+GG genotype, a clinical characteristics analysis also showed a female-specific association in category instances (t = 2.76, p = 0.042, FDR corrected).Conclusion: The polymorphisms within the MIR137 gene are associated with susceptibility to schizophrenia, and a female-specific association of MIR137 with schizophrenia was reported in a Han Chinese population.

Our previous study suggested that the synapse-associated protein 97 (SAP97) gene rs3915512 polymorphism may influence neurocognition in schizophrenia patients. Neuroimaging studies have shown a possible association between cognitive function and brain activity/connectivity. Considering the poor understanding of whether the disease state and SAP97 rs3915512 polymorphism have interactive effects on brain activity/connectivity, 52 first-episode schizophrenia (FES) patients and 52 healthy controls were genotyped using blood DNA samples and underwent magnetic resonance imaging scanning. A two-way ANCOVA model was performed with rs3915512 genotypes and disease state as the between-subject factors. A significant disease × SAP97 interactive effect was found for the amplitude of low-frequency fluctuation (ALFF) in the right supplementary motor area, left rolandic opercularis area (ROC-L), and bilateral middle occipital gyrus (MOG). In addition, among auditory/visual-related brain areas, a significant interactive effect was found for resting-state functional connectivity (RSFC) between the MOG-L and bilateral superior temporal gyrus (STG) in the STG-L with ROC-R, right cuneus (Cu-R), left fusiform (Fu-L), and left lingual gyrus (LG-L). Positive correlations were found between ALFF in the ROC-L and motor speed scores, between RSFC in the STG-L and LG-L and between Brief Assessment of Cognition in Schizophrenia verbal memory scores in FES. The SAP97 rs3915512 polymorphism may affect neurocognitive function in patients with schizophrenia by changing the brain activity and connectivity of auditory/visual-related brain areas.

The nonstructural protein 10 (nsp10) of porcine reproductive and respiratory syndrome virus (PRRSV) encodes for helicase which plays a vital role in viral replication. In the present study, a truncated form of nsp10, termed nsp10a, was found in PRRSV-infected cells and the production of nsp10a was strain-specific. Mass spectrometric analysis and deletion mutagenesis indicated that nsp10a may be short of about 70 amino acids in the N terminus of nsp10. Further studies by rescuing recombinant viruses showed that the Glu-69 in nsp10 was the key amino acid for nsp10a production. Finally, we demonstrated that nsp10a exerted little influence on the growth kinetics of PRRSV in vitro.

Afterglow brightness represents one of the most important characteristics in the application of afterglow materials. High molar absorption coefficient, high afterglow efficiency, and long afterglow lifetimes are required to achieve intense afterglow. However, current strategies cannot simultaneously fulfill these requirements due to specific intrinsic problems. Here, based on the understanding of difluoroboron β‐diketonate systems, the manipulation of higher triplet excited states is conceived to selectively enhance intersystem crossing with phosphorescence lifetimes remaining long. Aromatic substrates, which possess specific HOMO levels and T1 levels, are selected for relay synthesis to form difluoroboron β‐diketonate compounds with very close‐lying S1 and T2 levels; according to the energy gap law, such systems exhibit strong intersystem crossing. Upon doping into rigid matrices, the resultant difluoroboron β‐diketonate systems display the brightest ambient afterglow that has ever been observed. [ABSTRACT FROM AUTHOR]

Purpose This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC. [ABSTRACT FROM AUTHOR]

Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy. [ABSTRACT FROM AUTHOR]

Metal core@semiconductor shell hybrids are regarded as promising candidates for plasmon-enhanced photocatalysis, but it remains a challenge to build semiconductor junctions on the shell region for further improved photocatalysis. Herein, Au core@dual-semiconductor coshell hybrids, whose shell was made by two different metal sulfides, were prepared by a one-pot direct growth method based on Au nanorods for highly improved photocatalysis for the first time. By inducing two different metal ions at the step of shell growth in a surfactant-assisted hydrothermal reaction, three types of Au@dual-semiconductor hybrids were prepared. In these hybrids, Au and two semiconductors intimately contact with each other, and three types of semiconductor heterojunctions including type I (ZnS–CdS), type II (Cu2–xS–Bi2S3), and Z-scheme (Bi2S3–CdS) are grown on Au nanorods. The as-prepared Au@dual-semiconductor hybrids show excellent photocatalytic activity on degrading rhodamine B under light irradiation, which is much higher than that of Au@single-semiconductor, semiconductor junctions, and Au@semiconductor@semiconductor hybrids with a double-layer shell. The enhanced mechanism can be ascribed to the accelerated carrier transfer and separation driven by the internal electric fields (IEFs) between semiconductors. Meanwhile, the plasmon-induced hot electron injection from Au to semiconductors can be promoted due to the cooperation of the Schottky junction or ohmic contact at metal–semiconductor interfaces and IEFs at semiconductor–semiconductor interfaces, which further promote the photocatalysis. [ABSTRACT FROM AUTHOR]