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Rare-earth-mediated selective endocyclic and exocyclic Si–C(sp3) bond cleavage of a silyl-modified silylamido ligand was realized through the nucleophilic addition of unsaturated molecules such as CO, CS2, and organonitriles.

Background: The vibration isolation platform (VIP) can greatly reduce the risk of damage to dynamic equipment caused by external vibration interference and provide the most stable and reliable working environment for dynamic equipment. Objective: Aiming at the problems of small vibration isolation dimension, low bearing capacity, serious motion coupling, and narrow vibration isolation bandwidth in the field of vibration isolation of dynamic load equipment, a hydraulic redundant six degrees of freedom parallel vibration isolation platform (PVIP) with active and passive composite vibration isolation support is proposed. Methods: The dynamic coupling model of active and passive hybrid vibration isolation (APHVI) of redundant PVIP is established, and the matrix diagonal decoupling control strategy and fuzzy PI control theory are combined. Analysis of passive vibration isolation performance and APHVI performance of VIP is done. Results: The simulation results show that the effect of APHVI based on fuzzy PI decoupling control is better than that of passive vibration isolation and matrix diagonal decoupling control. Conclusion: Fuzzy PI control can effectively attenuate more than 98 % of the disturbance, significantly improve the vibration isolation performance and decoupling effect of the platform, and expand the effective vibration isolation bandwidth.

Current action mechanisms for aptamer-based therapeutics depend on occupancy-driven pharmacology to mediate protein functions. We report a new mechanism where aptamers leverage cellular proteasomal degradation system to degrade proteins for cancer treatment. A DNA aptamer (hereinafter referred to as c-Met-Ap) binds to the extracellular domain of mesenchymal-epithelial transition factor (c-Met) and selectively induces c-Met phosphorylation at Y1003 and Y1349. The phosphorylation of Y1003 recruits E3 ubiquitin ligase casitas B-lineage lymphoma, causing c-Met ubiquitination and degradation in the proteasome. Furthermore, c-Met-Ap can induce a decrease in the heterodimeric partner proteins of c-Met and the downstream effector proteins in the c-Met signal axis, effectively inhibiting tumor growth in A549 tumor-bearing BALB/c mice. Our study uncovers a novel, actionable mechanism for aptamer therapeutics and opens a new avenue for developing highly efficient anticancer drugs.

AIM: To obtain the baseline data on presenting visual acuity (PVA) and evaluate the prevalence and associated factors for visual impairment based on PVA in 9070 Chinese college students. METHODS: The freshmen at a university in southern China, including 6527 undergraduate students and 2543 graduate students, were investigated for some socio-demographic characteristics and underwent routine medical examination, including measuring PVA, height, and weight. Visual impairment was defined according to the new World Health Organization criteria for blindness and visual impairment. RESULTS: In 9070 college students, the mean PVA in the better eye was 0.094±0.163 logMAR. The prevalence of visual impairment based on PVA was 2.7%. Only 38.3% college students had normal visual acuity [PVA equal to 0 logMAR (20/20) in both eyes]. There were 69.8% of students wearing spectacles. Logistic regression showed that home region (non-Guangdong provinces, P

PurposeTo evaluate the contributions of human leucocyte antigen (HLA) class I and II genes in the development of Graves’ ophthalmopathy (GO) in a Southern Chinese population.MethodsEight HLA loci were genotyped and analysed in 272 unrelated patients with Graves’ disease (GD) or the proptosis and myogenic phenotypes of GO, and 411 ethnically matched control subjects.ResultsThe allele frequencies of HLA-DRB1*16:02 and -DQB1*05:02 in the GD, proptosis and myogenic groups, HLA-B*38:02 and -DQA1*01:02 in the myogenic group were significantly higher than those in the control group, respectively (all corrected p values 2.5). The haplotype frequencies of HLA-DRB1*16:02-DQA1*01:02-DQB1*05:02 and HLA-DRB1*16:02-DQA1*01:02-DQB1*05:02-DPA1*02:02-DPB1*05:01 in the proptosis and myogenic groups, and HLA-A*02:03-B*38:02-C*07:02 and HLA-A*02:03-B*38:02-C*07:02-DRB1*16:02-DQA1*01:02-DQB1*05:02-DPA1*02:02-DPB1*05:01 in the myogenic group were significantly higher than those in the control group respectively (all corrected p values 2.5). The potential epitopes (‘FLGIFNTGL’ of TSHR, ‘IRHSHALVS’, ‘ILYIRTNAS’ and ‘FVFARTMPA’ of IGF-1R) were fitted exactly in the peptide-binding groove between HLA-DRA1-DRB1*16:02 heterodimer, and the epitopes (‘ILEITDNPY’ of THSR, ‘NYALVIFEM’ and ‘NYSFYVLDN’ of IGF-1R) were also fitted exactly in the peptide-binding groove between HLA-DQA1*01:02-DQB1*05:02 heterodimer.ConclusionsThe HLA-DRB1*16:02 and -DQB1*01:02 alleles might be risk factors for GD including the proptosis and myogenic phenotypes of GO. The alleles HLA-B*38:02, -DQA1*01:02, the HLA haplotypes consisting of HLA-B*38:02, -DRB1*16:02, -DQA1*01:02 and -DQB1*05:02 might be susceptibility risk factors for GO. Simultaneously, some epitopes of TSHR and IGF-1R tightly binding to groove of HLA-DRA1-DRB1*16:02 or HLA-DQA1*01:02-DQB1*05:02 heterodimers might provide some hints on presenting the pathological antigen in GO.

Purpose. Based on the differential gene expression analysis for predictive biomarkers with RNA-Sequencing data from Fuchs endothelial corneal dystrophy (FECD) patients, we are aiming to evaluate the efficacy of Library of Integrated Network-based Cellular Signatures (LINCS) perturbagen prediction software to identify novel pharmacotherapeutic targets that can revert the pathogenic gene expression signatures and reverse disease phenotype in FECD. Methods. A publicly available RNA-seq dataset was used to compare corneal endothelial specimens from controls and patients with FECD. Based on the differential gene expression analysis for predictive biomarkers, we evaluated the efficacy of LINCS perturbagen prediction software to identify novel therapeutic targets that can revert the pathogenic gene expression signatures and reverse disease phenotypes in FECD. Results. The RNA-seq dataset of the corneal endothelial cells from FECD patients revealed the differential gene expression signatures of FECD. Many of the differential expressed genes are related to canonical pathways of the FECD pathogenesis, such as extracellular matrix reorganization and immunological response. The expression levels of genes VSIG2, IL18, and ITGB8 were significantly increased in FECD compared with control. Meanwhile, the expression levels of CNGA3, SMOX, and CERS1 were significantly lower in the FECD than in control. We employed LINCS L1000 Characteristic Direction Signature Search Engine (L1000-CDS2) to investigate pathway-based molecular treatment. L1000-CDS2 predicted that small molecule drugs such as histone deacetylase (HDAC) inhibitors might be a potential candidate to reverse the pathological gene expression signature in FECD. Conclusions. Based on differential gene expression signatures, several candidate drugs have been identified to reverse the disease phenotypes in FECD. Gene expression signature with LINCS small molecule prediction software can discover novel preclinical drug candidates for FECD.

Viral myocarditis (VMC) is a type of inflammation affecting myocardial cells caused by viral infection and has been an important cause of dilated cardiomyopathy (DCM) worldwide. Type B3 coxsackievirus (CVB3), a non-enveloped positive-strand RNA virus of the Enterovirus genus, is one of most common agent of viral myocarditis. Till now, effective treatments for VMC are lacking due to lack of drugs or vaccine. Lithium chloride (LiCl) is applied in the clinical management of manic depressive disorders. Accumulating evidence have demonstrated that LiCl, also as an effective antiviral drug, exhibited antiviral effects for specific viruses. However, there are few reports of evaluating LiCl's antiviral effect in mice model. Here, we investigated the inhibitory influence of LiCl on the CVB3 replication in vitro and in vivo and the development of CVB3-induced VMC. We found that LiCl significantly suppressed CVB3 replication in HeLa via inhibiting virus-induced cell apoptosis. Moreover, LiCl treatment in vivo obviously inhibited virus replication within the myocardium and alleviated CVB3-induced acute myocarditis. Collectively, our data demonstrated that LiCl inhibited CVB3 replication and negatively regulated virus-triggered inflammatory responses. Our finding further expands the antiviral targets of LiCl and provides an alternative agent for viral myocarditis.

In this paper, the structural equation model is used to investigate the factors that affect the satisfaction of college students with Jingdong (JD) logistics. Based on the Swedish customer satisfaction index (SCSI) model and the American customer satisfaction index (ACSI) model, combined with their own actual needs, the model of college students’ satisfaction with JD Logistics is redefined. In this way, the scale indicators of the questionnaire survey are set. Combined with the research and empirical analysis of relevant literature, the initial model hypothesis was constructed, and six path hypotheses were proposed. The reliability and validity analysis confirmed that the questionnaire scale had high reliability and structural validity, and the structural equation model is also carried out. The fitting degree test confirmed that the structural equation hypothesis model has a high degree of fit, and verified the hypothesis established in the article, and finally put forward some countermeasures and suggestions for improving the service system of JD Logistics.

The oxidation behavior of the alloy Fe−25%Cr−6%Al-RE (rich in lanthanum) was investigated by means of TEM analysis. The results show that after 2 hr oxidation of the alloy, in pure oxygen at 1200° C, La precipitated in the oxide scale at the top of α-Al2O3 grains and at the grain-boundary regions in the form of tiny particles of hexagonal La2O3. These tiny particles prevented aluminum from diffusing toward the surface and suppressed lateral growth of the oxide scale. The rare-earth constituents accelerated the internal oxidation of the alloy during thermal cycling between 1200° C and room temperature. They appeared as particles of aluminum oxide and lanthanum oxide. Particles of cubic La2O3 precipitated in the alloy matrix near the oxide scale-metal interface in a direction parallel to grain boundaries.

Ferritic stainless steels containing intermediate to h igh interstitial contents (greater than 200 wppm total C + N ) exhibit severe embritt!ement after heating to 950°C and cooling rapidly to room temperature [1, 2]. The underlying cause in type 446 stainless steel is the rapid precipitation of Cr carbides and nitrides at grain boundaries and dislocation sites during cooling from temperatures above 950 °C, where the interstitial atoms are in solution [2]. The complex nature of carbonitride precipitation in Fe-Cr alloys has been the subject of several previous studies of 475 °C embrittlement reaction [1, 3 6]; formation of Cr2N was reported within the first few hours of ageing [3, 4], Fe and C may substitute partially for Cr and N in Cr2N (M2X) [4], and the metastable M2X precipitates coarsen with prolonged ageing and transition to Cr23X6 occurs [5]. Spear et al. proposed that the sequence of interstitial precipitation processes in FeCrA1 alloys is MX--~ M2X---~,M23X 6 [1]. In this work, interstitial preCipitation in a Fe25Cr5A1 alloy has been indentified during ageing at 600°C and thermal cycling treatment processes. The ingot of Fe25Cr5A1 alloy was prepared by induction melting. After homogenizing, the alloy was rolled into rod 8 mm in diameter with intermediate anneals. The altoy chemical composition was (wt %) Cr 24.61, A1 4.91, Mn 0.11, Si 0.35, C 0.038, N 0.007, S 0.002, P 0.015, Ti 0.3, mixed rare earth 0.05, and Fe balance. All alloy specimens were cut from the rod and were solution heated at 1200 °C in air before quenching in water. The programme of thermai cycling treatment used involved heating in air for 3 min at 1200 °C and cooling in air at a rate of 2.8 °C/s for a period which allowed all specimens to cool to ambient temperature. A small amount of residue extracted from the specimens was examined by X-ray diffraction. Thin foils of the alloy specimens for transmission electron microscopy (TEM) studies were prepared by standard procedures and the foils examined in a Philips 400 TEM with an electron accelerating voltage Of 100kV and an incident electron probe diameter of approximately 40 nm; energy-dipersive X,ray spectroscopy (EDS) was used to enable X-ray microanalysis of the specimens. TEM investigation indicates that there is no precipitation at grain boundaries in the alloy quenched from 1200 °C as shown in Fig. 1. A small amount of intragranular blocky TiN is present in the alloy. The matrix of the alloy has a bcc structure (a