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Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths in the world. The downregulation of farnesoid X receptor (FXR) is frequently founded in CRC patients. The current study found that the decreased expression of FXR in colorectal cancer leads to disorders of bile acids (BAs) metabolism. The altered BAs profile shaped distinct intestinal flora and positively regulated secretory immunoglobulin A (sIgA). The dual regulation of BAs and sIgA enhanced adhesion and biofilm formation of enterotoxigenic Bacteroides fragilis (ETBF), which has a colorectal tumorigenesis effect. The abundance of ETBF increased significantly in intestinal mucosa of colitis-associated cancer (CAC) mice, and finally promoted the development of colorectal cancer. This study suggests that downregulation of FXR in CRC results in BAs dysregulation, and BAs have strong effects on sIgA and gut flora. The elevated BAs concentration and altered gut microbiome are risk factors for CRC.

Nursing home residents’ well-being is often proxy-rated in studies, and few studies have explored the association between resident-rated person-centered climate, garden greenery, and resident-rated well-being. A cross-sectional study was conducted. Questionnaire data from a convenient sample of 470 nursing home residents in a city in Southeast China in 2021 were analyzed using multiple linear regressions, with block-wise models. The instruments used were the Person-centered Climate Questionnaire-Patient version, the Nursing Home Greenery Index, and, for well-being, the EuroQol-Visual Analogue Scale, the Life Satisfaction Questionnaire, and the 9-item Patient Health Questionnaire (depression symptoms). In the unadjusted models, the person-centered climate was positively associated with general health (β 0.29, p < 0.001), person-centered climate and greenery with life satisfaction (β 0.39, and 0.18; both p < 0.001), and negatively with depression (β −0.28, and β −0.23, both p < 0.001). After adjusting for personal and nursing home characteristics, the associations between person-centered climate, greenery, and well-being remained statistically significant. The three models explained 36%, 35%, and 21% of the variance in general health, life satisfaction, and depression, respectively. This study provides knowledge on person-centered climate in long-term care and the access to greenery.

Objectives. Hyperhomocysteinemia (HHcy) is an easily neglected disease, which can be hidden in the body for many years without signs or symptoms. We want to explore the causes of HHcy, the correlation of HHcy with micronutrients, lifestyle, dietary habits and HHcy related genes, preventing the occurrence of HHcy.Methods. 800 subjects (M/F, 403/397) were divided into normal Hcy and HHcy group according to the plasma levels of Hcy, compared essential characteristics by questionnaires, genetic polymorphism tested by Realtime PCR and micronutrients detected by mass spectrometry. The statistical analysis methods were Chi - square tests, ANOVA, logistic regression. This trial has been registered with the trial number ChiCTR1900025136. Results. 42.66% of 143 HHcy cases were aged from 10 to 18, with higher levels of zinc (Zn), vitamin A, Uric acid (P < 0.05) and a lower level of 25-OH-D3, VB12, folic acid (Fol) (P < 0.05) compared to the normal group. The multivariate logistic regression significantly predicted HHcy development containing higher level of Zinc (Exp(B) = 1.042; 95% CI, 1.000 - 1.086), higher Uric (Exp(B) = 1.014; 95% CI, 1.008 - 1.019), lower B12 (Exp(B) = 0.993; 95%CI, 0.989 - 0.997), lower Folic acid (Exp(B) = 0.772; 95% CI, 0.657 - 0.907), and polymorphism of MTHFR C677T (Exp(B) = 2.923; 95% CI, 1.399–6.107).Conclusion. Pay more attention to those students who were facing great pressure because they are very likely to be potential HHcy patients with high levels of uric acid and zinc and anxiety.

Adaptive intervention(AI)is a methodology which dynamically evaluates adaptive variables at decision points and timely adjusts and develops tailored strategies to meet individual needs.The study reviewed the origin and development and elaborated the core elements(including intervention outcomes,intervention options,decision points,tailoring variables,and decision rules)and the classification of AI.Based on the literature,the key points of the design and implementation of AI were prospected,which can provide evidence for the research and development of health behavior intervention.

Aiming at the problems of large consumption of new coronavirus detection materials and high risk of infection, a virtual training system for new coronavirus detection is designed and developed based on virtual reality technology. The system establishes a 3D model of new coronavirus detection scene and medical equipment, and simulates the process of pre detection, diagnosis, wearing protective clothing and nucleic acid collection. Combined with the system evaluation function, it can effectively improve the learning interest and efficiency.The results show that the irreversible medical operation with high risk of infection and the practice that is difficult to practice on site at ordinary times can be converted into the operation that can be practiced repeatedly.It has a certain reference significance to explore the application of virtual reality technology in medical training.

Background Mesenchymal stem cells (MSCs) have a therapeutic effect on diabetic nephropathy (DN) but the underlying mechanism remains unclear. This study was conducted to investigate whether human umbilical cord-MSCs (hUCMSCs) can induce oxidative damage and apoptosis by activating Nrf2. Methods We used a type 2 diabetic rat model and a high-glucose and fat-stimulated human glomerular mesangial cell (hGMC) model. Western blotting, RT-qPCR, and TUNEL staining were performed on animal tissues and cultured cells. Nuclear expression of Nrf2 was detected in the renal tissue. Furthermore, Nrf2 siRNA was used to examine the effects of hUCMSCs on hGMCs. Finally, the effect of hUCMSCs on the Nrf2 upstream signalling pathway was investigated. Results After treatment with hUCMSCs, Nrf2 showed increased expression and nuclear translocation. After Nrf2-specific knockout in hGMCs, the protective effect of hUCMSCs on apoptosis induced by high-glucose and fat conditions was reduced. Activation of the PI3K signalling pathway may be helpful for ameliorating DN using hUCMSCs. Conclusions hUCMSCs attenuated renal oxidative damage and apoptosis in type 2 diabetes mellitus and Nrf2 activation is one of the important mechanisms of this effect. hUCMSCs show potential as drug targets for DN.

As a new precision processing technology, laser polishing is widely used in metal and non-metal. Laser polishing technology is especially suitable for parts with high hardness and small size. In this paper, a full factor experimental were carried out to investigate the effect of continues wave laser with a wavelength of 1064nm on the surface quality of additive manufacturing Ti6Al4V. The experimental result shows that a smooth surface can be obtained and the average roughness is reduced from 14.95μm to 1.756μm with the reduction rate is as high as 88.3% when laser power is 170W and scan speed is 60mm/s. And the height of the peaks and valleys on the sample surface has also been greatly reduced in condition of the optimized laser processing parameters.

Coronavirus disease 2019 (COVID-19) has become a global public health concern. We aimed to study the cytokine profile during the convalescent phase and its association with liver functions. We performed a retrospective study to investigate the longitudinal dynamic serum cytokine, liver function, and metabolomic profiles, as well as their potential correlations, from the viral replication phase to early convalescence. Our results demonstrated that liver injury was common. Liver injury was significantly associated with higher levels of interleukin (IL)-6 and IL-10 (p < 0.05). However, alanine aminotransferase levels decreased during the first week after hospital discharge (p < 0.01). In parallel, T-cell and B-cell immune response-stimulating cytokine IL-4, but not IL-2, was significantly elevated (p < 0.05). Furthermore, interferon-γ (IFN-γ) and tumor necrosis factor-α (TFN-α) levels increased, in contrast to the decrease in IL-6 and IL-10 levels; liver function returned to normal. The metabolomic analysis supported active recovery during early convalescence of COVID-19 patients that had distinct metabolic profiles associated with the hepatic tricarboxylic acid cycle, amino acid metabolism, and lipid metabolism. In addition, we identified a metabolomic association of IL-4 with liver repair. Our findings suggest that discharged patients continue to recover from the physiological effects of COVID-19, and the association of IL-4, IL-6, and IL-10 levels with metabolic changes and liver function repair may have important implications for clinical manifestations and treatment of COVID-19.

Wearable electronics, electronic skins, and human-machine interfaces demand flexible sensors with not only high sensitivity but also a wide linear working range. The latter remains a great challenge and has become a big hurdle for some of the key advancements imperative to these fields. Here, we present a flexible capacitive pressure sensor with ultrabroad linear working range and high sensitivity. The dielectric layer of the sensor is composed of multiple layers of double-sided microstructured ionic gel films. The multilayered structure and the gaps between adjacent films with random topography and size enhance the compressibility of the sensor and distribute the stress evenly to each layer, enabling a linear working range from 0.013 to 2063 kPa. Also, the densely distributed protrusive microstructures in the electric double layer contribute to a sensitivity of 9.17 kPa

Lung cancer patients with malignant pleural effusions (MPE) have a particular poor prognosis. It is crucial to distinguish MPE from benign pleural effusion (BPE). The present study aims to develop a rapid, convenient and economical diagnostic method based on FTIR near-infrared spectroscopy (NIRS) combined with machine learning strategy for clinical pleural effusion classification. NIRS spectra were recorded for 47 MPE samples and 35 BPE samples. The sample data were randomly divided into train set (n = 62) and test set (n = 20). Partial least squares, random forest, support vector machine (SVM), and gradient boosting machine models were trained, and subsequent predictive performance were predicted on the test set. Besides the whole spectra used in modeling, selected features using SVM recursive feature elimination algorithm were also investigated in modeling. Among those models, NIRS combined with SVM showed the best predictive performance (accuracy: 1.0, kappa: 1.0, and AUCROC: 1.0). SVM with the top 50 feature wavenumbers also displayed a high predictive performance (accuracy: 0.95, kappa: 0.89, AUCROC: 0.99). Our study revealed that the combination of NIRS and machine learning is an innovative, rapid, and convenient method for clinical pleural effusion classification, and worth further evaluation.

Stellera chamaejasme L. is a traditional Chinese medicine with a long history to treat stubborn skin ulcer, and it also has antiviral and antitumor effects. Neochamaejasmine B (NCB), Neochamaejasmine A (NCA) and Chamaechromone (CMC) are the major components in dried roots of Stellera chamaejasme L.. Our studies suggested that NCB, NCA and CMC are inhibitors of Organic anion transporter 1 (OAT1). OAT1 is encoded by solute carrier family 22 member 6 gene (SLC22A6) in humans and plays a critical role in the organic anion drug uptake and excretion in the kidney. Lamivudine is the typical substrate of OAT1 and is frequently used in combination with other antiviral drugs in clinical antiviral treatments. The aim of this study is to investigate the interaction and its mechanism between these bi-flavone components in Stellera chamaejasme L. and lamivudine via OAT1 both in vitro and in vivo. In vitro, the uptake studies in Madin-Darby canine kidney (MDCK) cells overexpressing OAT1 suggested that NCB inhibited the uptake of 6-CFL and lamivudine.Similar results were obtained for NCA and CMC. NCB was a noncompetitive and competitive inhibitor interaction with OAT1. IC50 values of NCB, NCA and CMC for inhibiting OAT1-mediated lamivudine transport were 2.46, 8.35 and 0.61 μmol·L-1, respectively. In vivo, the pharmacokinetic results of lamivudine in rats showed that the mean area under the plasma concentration-time curve (AUC0-∞) and maximal plasma concentration (Cmax) of lamivudine after co-administration is increased 2.94-fold and 1.87-fold, respectively, compared to lamivudine administration alone. The results of interactions between lamivudine and these bi-flavone components in Stellera chamaejasme L. extracts via OAT1 in vivo are consistent with studies in vitro. The inhibition of OAT1-mediated uptake of lamivudine by NCB, NCA and CMC is the possible mechanism for Stellera chamaejasme L. extracts improving the oral bioavailability of lamivudine in rats.

Purposes: To assess the effects of Tai Chi on quality of life (QOL) of cancer survivors. Methods: The following databases were searched: PubMed, Cochrane CENTRAL, EBSCO (including MEDLINE, CINAHL, and other databases), ScienceDirect, CNKI, Wangfang Data, and CQVIP until April 25, 2018. Randomized controlled trials (RCTs) published in English or Chinese examining the effects of Tai Chi intervention for cancer survivors were included. The primary outcome was QOL; the secondary outcomes were limb function/muscular strength, immune function indicators, cancer-related fatigue (CRF), and sleep disturbance. Methodological quality was assessed using the Cochrane Risk of Bias tool. Results of RCTs were pooled with mean difference (MD) or standardized mean difference (SMD) with 95% confidence intervals (CI). Quality of evidence for each outcome was assessed with the GRADE system. Results: Twenty-two RCTs were included in this review. Tai Chi improved the physical (SMD 0.34, 95%CI 0.09, 0.59) and mental health (SMD 0.60, 95%CI 0.12, 1.08) domains of quality of life. The intervention improved the limb/muscular function of breast cancer survivors (SMD 1.19, 95%CI 0.63, 1.75) and in mixed samples of cancer survivors reduced the levels of cortisol (MD − 0.09, 95%CI − 0.16, − 0.02), alleviated CRF (SMD − 0.37, 95%CI − 0.70, − 0.04), and promoted sleep (SMD − 0.37, 95%CI − 0.72, − 0.02). Conclusion: There is low-level evidence suggesting that Tai Chi improves physical and mental dimensions of QOL and sleep. There is moderate-level evidence suggesting Tai Chi reduces levels of cortisol and CRF and improves limb function. Additional studies with larger sample sizes and with higher-quality RCT designs comparing different regimens of Tai Chi are warranted.

Background:Sodium Taurocholate Co-transporting Polypeptide (NTCP) and Bile Salt Export Pump (BSEP) play significant roles as membrane transporters because of their presence in the enterohepatic circulation of bile salts. They have emerged as promising drug targets in related liver disease.Methods:We reviewed the literature published over the last 20 years with a focus on NTCP and BSEP.Results:This review summarizes the current perception about structure, function, genetic variation, and regulation of NTCP and BSEP, highlights the effects of their defects in some hepatic disorders, and discusses the application prospect of new transcriptional activators in liver diseases.Conclusion:NTCP and BSEP are important proteins for transportation and homeostasis maintenance of bile acids. Further research is needed to develop new models for determining the structure-function relationship of bile acid transporters and screening for substrates and inhibitors, as well as to gain more information about the regulatory genetic mechanisms involved in the processes of liver injury.

Retrospective survival analysis of 44 undifferentiated high grade pleomorphic sarcoma (UPS) of the spine.To identify factors related to overall survival (OS) and help decision making in the treatment of undifferentiated high grade pleomorphic sarcoma of the spine.UPS is an aggressive malignant tumor rarely originating from the spine. Due to its scarcity, only a few studies had been reported to describe the clinical features, treatments, and outcomes of sporadic cases, devoid of evaluation on prognostic factors.Enrolled in this survival analysis were 44 patients who underwent surgery and adjuvant therapies from January 1999 to December 2015. Kaplan-Meier methods were applied to estimate the overall survival. A multivariate Cox algorithm was applied to recognize factors independently associated with overall survival.Multivariate analysis suggested that age greater than or equal to 55 years (hazard ratio [HR], 3.923, P 0.001), Eastern Cooperative Oncology Group (ECOG) score four (HR, 4.656, P 0.001), and subtotal resection or piecemeal total resection (HR, 4.375, P 0.001) were independently associated with poor overall survival.We identified independent prognostic factors of UPS of the spine. Subtotal resection or piecemeal total resection, age more than or equal to 55 years and ECOG score four are factors adversely affecting overall survival of patients with UPS of the spine.4.

Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) patients who progress to end-stage renal disease (ESRD). With the increasing incidence of CKD, it is of importance to develop effective therapies that blunt development of renal fibrosis. FFNT25 is a newly developed molecular compound that could be used to prevent fibrosis. In this study, we administered FFNT25 to rats following unilateral ureteral obstruction (UUO) to investigate its anti-fibrosis mechanism. Thirty-two Sprague-Dawley rats were randomly divided into four groups: (1) control (normal rats), (2) sham-operated, (3) UUO-operated + vehicle, and (4) UUO-operated + FFNT25. Two weeks after UUO, the rats were gavaged with either FFNT25 (20.6 mg/kg/day) or vehicle for two weeks. Serum, urine, and kidney samples were collected at the end of the study. FFNT25 reduced levels of renal fibrosis and decreased mRNA and protein levels of extracellular matrix (ECM) markers α-smooth muscle actin (α-SMA) and plasminogen activator inhibitor-1 (PAI-1) following UUO compared to vehicle treatment (n = 8, p

The pathogenesis of multiple sclerosis (MS) is significantly regulated by long noncoding RNAs (lncRNAs), the expression of which is substantially influenced by a number of MS-associated risk single nucleotide polymorphisms (SNPs). It is thus hypothesized that the dysregulation of lncRNA induced by genomic variants may be one of the key molecular mechanisms for the pathology of MS. However, due to the lack of sufficient data on lncRNA expression and SNP genotypes of the same MS patients, such molecular mechanisms underlying the pathology of MS remain elusive. In this study, a bioinformatics strategy was applied to obtain lncRNA expression and SNP genotype data simultaneously from 142 samples (51 MS patients and 91 controls) based on RNA-seq data, and an expression quantitative trait loci (eQTL) analysis was conducted. In total, 2383 differentially expressed lncRNAs were identified as specifically expressing in brain-related tissues, and 517 of them were affected by SNPs. Then, the functional characterization, secondary structure changes and tissue and disease specificity of the cis-eQTL SNPs and lncRNA were assessed. The cis-eQTL SNPs were substantially and specifically enriched in neurological disease and intergenic region, and the secondary structure was altered in 17.6% of all lncRNAs in MS. Finally, the weighted gene coexpression network and gene set enrichment analyses were used to investigate how the influence of SNPs on lncRNAs contributed to the pathogenesis of MS. As a result, the regulation of lncRNAs by SNPs was found to mainly influence the antigen processing/presentation and mitogen-activated protein kinases (MAPK) signaling pathway in MS. These results revealed the effectiveness of the strategy proposed in this study and give insight into the mechanism (SNP-mediated modulation of lncRNAs) underlying the pathology of MS.

Protein–protein interactions (PPIs) governing the recognition of substrates by E3 ubiquitin ligases are critical to cellular function. There is significant therapeutic potential in the development of small molecules that modulate these interactions; however, rational design of small molecule enhancers of PPIs remains elusive. Herein, we report the prospective identification and rational design of potent small molecules that enhance the interaction between an oncogenic transcription factor, β-Catenin, and its cognate E3 ligase, SCFβ-TrCP. These enhancers potentiate the ubiquitylation of mutant β-Catenin by β-TrCP in vitro and induce the degradation of an engineered mutant β-Catenin in a cellular system. Distinct from PROTACs, these drug-like small molecules insert into a naturally occurring PPI interface, with contacts optimized for both the substrate and ligase within the same small molecule entity. The prospective discovery of ‘molecular glue’ presented here provides a paradigm for the development of small molecule degraders targeting hard-to-drug proteins., Directed protein degradation to target hard-to-drug proteins is a promising therapeutic approach. Here, the authors report the prospective discovery of small molecule “molecular glue” that inserts into a naturally occurring E3 ligase-substrate interface leading to degradation of substrate protein.

Acute lung injury (ALI) is a type of diffuse lung inflammation with a high mortality rate. Studies show that miR-155 plays an important role in inflammation. Here, we investigated the role of miR-155 in lipopolysaccharide (LPS)-induced ALI. The mice with bone marrow transplantation between MiR-155 knockout and wild-type were used as animal models of LPS-induced sepsis. In response to LPS injection, ALI was less severe in miR-155 knockout mice than in wild-type mice, and mainly manifested as reduced pulmonary vascular leakage, pulmonary edema, and neutrophil infiltration. The expression levels of Ang-2 and apoptosis-associated caspases-3 and -9, as well as myosin light chain (MLC) phosphorylation in the lungs were also decreased. A bone marrow transplantation experiment showed that miR-155 expressed in bone marrow-derived lymphocytes rather than lung parenchymal lymphocytes promoted inflammation. Findings suggest that miR-155 expressed in bone marrow-derived lymphocytes promoted LPS-induced ALI through the modulation of the Ang-2-Tie-2 pathway.

Histone deacetylase 6 (HDAC6) plays a key role in a variety of neurological disorders, which makes it attractive drug target for the treatment of Alzheimer's disease, Parkinson's disease, and memory/learning impairment. The selectivity of HDAC6 inhibitors (sHDAC6Is) are widely considered to be susceptible to the sizes of their Cap group and the physicochemical properties of their linker or zinc-binding group, which makes the discovery of new sHDAC6Is extremely difficult. With the discovery of the distinct selectivity between Trichostatin A (TSA) enantiomers, the chirality residing in the connective units between TSA's Cap and linker shows a great impact on its selectivity. However, the mechanism underlining ( S)-TSA's selectivity is still elusive, and the way chirality switches the selective ( S)-TSA to nonselective ( R)-TSA is unknown. In this study, multiple computational approaches were collectively applied to explore, validate, and differentiate the binding modes of two TSA enantiomers in HDACs (especially the HDAC6) at atomic level. First, two nonconservative residues (G200/M205 and Y197/F202 in HDAC1/6) in loop3 and four conservative residues deep inside the hydrophobic binding pocket were discovered as the decisive residues of ( S)-TSA's selectivity toward HDAC6. Then, a novel mechanism underlying the selectivity of ( S)-TSA toward HDAC6 was proposed, which was composed of the trigger by two nonconservative residues F202 and M205 in HDAC6 and a subsequently improved fit of ( S)-TSA deep inside HDAC6's hydrophobic binding pocket. TSA enantiomers were used as a molecular probe to explore the mechanism underlying sHDAC6Is' selectivity in this study. Because of their decisive roles in ( S)-TSA's selectivity to HDAC6, both F202 and M205 in HDAC6 should be especially considered in the discovery of novel sHDAC6Is.

In single-point diamond turning (SPDT), the workpiece centre error owing to the tool height below or above the spindle axis causes cylinder or cone appearances at the workpiece centre. The formed cone or cylinder boundary is used to identify the tool height and then compensate for it, in order to obtain the desired surface profile. As opposed to previous studies, based on the fact that the diamond tool is elevated during cone formation and therefore forms a tool interference zone with higher land and larger radius, this research conducts a theoretical and experimental study to investigate the origin of tool interference owing to centre error, and its influencing factors. In this study, the relation between centre error and interference force was investigated. A series of experiments were conducted to explore tool interference generation and its influencing factors. A mathematical model was derived to calculate the tool interference zone radius, whereby the relation between this radius and the cutting conditions was established. Moreover, the error sources between the theoretical and experimental results were analysed. As centre error can only be reduced by compensation and cannot be eliminated, particularly in machine tools with poor resolution, it is meaningful to conduct research on the centre cone generation and its influence on tool interference in SPDT, as well as suppressing the tool interference in SPDT. Furthermore, this research provides a reference for establishing an online force-based centre error identification method, thereby improving cutting efficiency.

Ewing's sarcoma family tumors (ESFTs) are the second most common malignancy in children and adolescents. The purpose of the present retrospective study was to evaluate the prognostic role of inflammatory biomarkers and preoperative D-dimer levels in patients with spinal ESFTs.The neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte ratio, albumin/globulin ratio, C-reactive protein/albumin ratio (CAR), preoperative D-dimer level, and clinical parameters were evaluated and analyzed. Univariate and multivariate analyses for disease-free survival (DFS) and overall survival (OS) were performed using the log-rank test and Cox regression analysis, respectively. The DFS and OS rates were calculated using the Kaplan-Meier method. Nomograms were established to predict DFS and OS quantitatively.The optimal cutoff values for D-dimer, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte ratio, CAR, and albumin/globulin ratio were 0.3, 3.2, 168, 2.2, 1.5, and 1.4, respectively. The patients were stratified into 2 groups according to the cutoff values. Multivariate analysis revealed that age, resection mode, and D-dimer level were favorable prognostic factors for DFS and OS (P0.05). Metastasis and CAR1.5 were significantly associated with OS (P 0.05). Nomograms with all significant factors were established to predict DFS and OS.Our results have indicated that the preoperative D-dimer level is an effective prognostic factor with discriminatory ability for DFS and OS, superior to other indicators. Also, CAR was favorable prognostic factor for OS. Nomograms of DFS and OS can be recommended as practical models to evaluate the prognosis for patients with spinal ESFTs.

Clear cell Renal Cell Carcinoma (ccRCC) is characterized in most cases (>80%) by the inactivation of von Hippel-Lindau (VHL) tumor suppressor. VHL loss leads to HIF2α accumulation and constitutive activation of its downstream genes important in carcinogenesis. Preclinical and clinical evidence demonstrate that HIF2α inhibition by the first-in-class belzutifan (MK-6482) offers an effective treatment for ccRCC. Here we discovered a novel, potent, selective, and orally available small molecule HIF2α inhibitor (NKT2152) through rational drug design. Cellular thermal shift assay demonstrated NKT2152 engaged HIF2α and stabilized it against heat-induced denaturation in ccRCC 786-O cells. NKT2152 disrupted HIF2α/HIF1β complex in a dose-dependent manner, resulting in increased cytosol localization and reduced nucleus localization of HIF2α in 786-O cells. In vitro, NKT2152 specifically suppressed the expression of HIF2α target genes including vascular endothelial growth factor A, cyclin D1, and glucose transporter 1 in 786-O cells. Pharmacodynamic analysis of NKT2152 in the 786-O xenograft tumor model confirmed that NKT2152 potently inhibited HIF2α as demonstrated by the repression of HIF2α-regulated genes at both mRNA and protein levels. Moreover, NKT2152 treatment, administrated twice daily by oral gavage, led to a dose-dependent tumor growth inhibition or tumor regression in both ccRCC cell line-derived (A498 and 786-O) and patient-derived xenograft tumor models. More pronounced tumor growth inhibition was observed when NKT2152 was combined with a VEGFR inhibitor or a CDK4/6 inhibitor in the 786-O xenograft tumor model. In addition to directly promoting tumor progression by regulating gene expression in tumor cells, HIF2α has also been proposed to play an integral role in shaping the tumor microenvironment under hypoxia. Given hypoxia is a hallmark of most solid tumors and is associated with poor survival in a wide range of cancer types, we tested the hypothesis that HIF2α inhibition by NKT2152 may exert broader anti-tumor activity in other solid tumors that lack a VHL gene deficiency. Indeed, we demonstrated here that NKT2152 caused significant tumor growth inhibition in multiple solid tumor xenograft models, including but not limited to hepatocellular carcinoma. NKT2152 had excellent oral bioavailability and achieved high exposures in mouse, rat and dog. These data not only support clinical development of NKT2152 in ccRCC, but also provide exciting opportunities for expanding to other solid tumor indications with tremendous unmet medical needs. Clinical evaluation of NKT2152 for the treatment of ccRCC is ongoing. Citation Format: Jing Lu, Hairong Wei, Wenfeng Sun, Jianlin Geng, Ke Liu, Jessica Liu, Zhihong Liu, Jiping Fu, Yigang He, Keshi Wang, Yan Lou, Zhenhai Gao. NKT2152: A highly potent HIF2α inhibitor and its therapeutic potential in solid tumors beyond ccRCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6330.

Breast cancer is prone to form bone metastases and subsequent skeletal‐related events (SREs) dramatically decrease patients’ quality of life and survival. Prediction and early management of bone lesions are valuable; however, proper prognostic models are inadequate. In the current study, we reviewed a total of 572 breast cancer patients in three microarray data sets including 191 bone metastases and 381 metastases‐free. Gene set enrichment analysis (GSEA) indicated less aggressive and low‐grade features of patients with bone metastases compared with metastases‐free ones, while luminal subtypes are more prone to form bone metastases. Five bone metastases‐related genes (KRT23, REEP1, SPIB, ALDH3B2, and GLDC) were identified and subjected to construct a gene expression signature‐based nomogram (GESBN) model. The model performed well in both training and testing sets for evaluation of breast cancer bone metastases (BCBM). Clinically, the model may help in prediction of early bone metastases, prevention and management of SREs, and even help to prolong survivals for patients with BCBM. The five‐gene GESBN model showed some implications as molecular diagnostic markers and therapeutic targets. Furthermore, our study also provided a way for analysis of tumor organ‐specific metastases. To the best of our knowledge, this is the first published model focused on tumor organ‐specific metastases.

In ultra-precision fly cutting (UPFC), steady tool wear progresses gradually when cutting ductile materials. The steady wear of diamond tools changes the tool geometry, and further affects the topography of the machined surface. In this study, a theoretical and experimental investigation was conducted on the forms of steady tool wear and their influence on the tool geometry in UPFC. The features of steady tool wear in UPFC were investigated, the displacement of the cutting edge under the effects of tool flank wear was modeled, and factors affecting the cutting edge roundness were investigated. The study results indicate the following: (1) the features of steady tool wear in UPFC include crater wear on the rake face, smooth and flat wear on the cutting edge, and flank wear on the tool clearance face. (2) A smooth wear-land on the cutting edge changes the top rake of the cutting tools, whereas flank wear on the tool clearance face affects the clearance angle and roundness of the cutting edge. (3) The maximum width of the tool material loss zone, the nose radius of the original fresh cutting edge, and the arc angle of the wear-land have a certain influence on the nose radius of the worn cutting edge. The results of this study will provide deep insight into steady tool wear and its influence on the tool geometry, which can potentially be used to predict or evaluate the finish of a machined surface under tool steady wear.

The current upper limits of normal (ULN) for serum alanine aminotransferase (ALT) are increasingly challenged. We aimed to re-evaluate the ULN for ALT and assess the potential impact on the classification of natural course of chronic hepatitis B virus (HBV) infection in children. Laboratory data obtained from three hospitals in China were retrospectively analysed. In total, 2054 children with chronic HBV infection and 8149 healthy children at age ≤18 years were included in the study. Age-specific and gender-specific ULNs for ALT, at averages of 30 U/L for boys and 24 U/L for girls, were calculated from the data of healthy children. Using the revised ULNs vs. the current ULNs (40–50 U/L), 31–60% vs. 9–17% of the 2054 HBV-infected children had an abnormal result as seen in their ALT baseline analysis, and the highest abnormality rate was seen in the infants. Data of 516 HBV-infected children were applied for the classification of clinical phase, 28.8% vs. 19.8% of the children were classified into the phases of hepatitis B e antigen (HBeAg-)positive/negative hepatitis. During a median follow-up of 62 months, 39 of 153 children underwent HBeAg seroconversion, whereas 3 of them had persistently “normal” ALT, according to the current ULN. The revision of ULN for ALT in children substantially impacts the classification of the natural course of chronic HBV infection. Mild ALT fluctuation is common during the stage childhood, suggesting a need to rethink the current conceptions of immune tolerance and natural course of chronic HBV infection in the children.

In 2018, a renal risk score of antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) based on estimated glomerular filtration rate (eGFR), normal glomeruli, and tubular atrophy/interstitial fibrosis (TA/IF) was proposed to predict renal outcomes. We aimed to evaluate this renal risk score in a myeloperoxidase (MPO)-ANCA predominant population in Northeast China.We retrospectively analyzed the clinicopathologic data of 65 patients biopsy-proven from a Chinese medical center. Each patient was assessed by eGFR, normal glomeruli, and TA/IF, and the renal outcome was evaluated using the renal risk score.In our study, 95.4% of patients were ANCA positive (78.5% MPO-ANCA positive and 16.9% proteinase 3-ANCA positive). The average follow-up period was 14.3 months. Thirty-four patients (52.3%) reached end-stage renal disease (ESRD). Based on the renal risk score, 8 (12.3%), 31 (47.7%), and 26 (40%) patients were divided into the low-risk, medium-risk, and high-risk groups, respectively. Kaplan-Meier survival curves revealed the high-risk group had worse renal outcomes than the low-risk group (p0.01) and the medium-risk group (p0.01), but the renal outcome did not differ between the low-risk and medium-risk groups (p0.017). Similar results were obtained by the competitive survival analysis. The AUC for 3-year overall ESRD predictions was 0.845. In the regression analysis, the renal risk score was a favorable predictor for the development of ESRD (HR 3.13, 95%CI 1.58-6.19, p=0.001).The renal risk score is a preferred index that can predict ESRD in Chinese AAGN patients, especially in the high-risk group with worse renal outcomes. Key Points • The eGFR and percentage of normal glomeruli were valuable predictors of renal outcome, whereas TA/IF was not. • We confirmed the renal risk score is a preferred index that can predict ESRD in Chinese AAGN patients. • Based on the renal risk score, the high-risk group had worse renal outcomes than the low-risk group and the medium-risk group.

Bacterial and viral infection is a common cause of pneumonia, respiratory failure, and even acute respiratory distress syndrome. Increasing evidence indicates that red blood cells (RBCs) may contribute to immune response and inflammation. However, the precise molecular mechanisms that link RBC and hemolysis to the development and progression of inflammatory pathologies are not entirely understood. In this study, we used bacterial endotoxin, lipopolysaccharide (LPS), to mimic an infectious hemolysis and found that RBCs dynamically regulated cell aggregation between immune cells and human lung microvascular endothelial cells (HLMVEC). When RBCs were treated with LPS, integrin α4β1 was increased and was accompanied by cytokines and chemokines release (TNF-α, IL-1β, IL-6, IL-8, IFN-γ, CXCL12, CCL5, CCL7 and CCL4). Upon α4β1 elevation, RBCs not only facilitated mature monocyte derived dendritic cell (mo-DCs) adhesion but also promoted HLMVEC aggregation. Furthermore, co-culture of the supernatant of LPS pre-treated RBCs with mo-DCs could promote naïve CD4 T cell proliferation. Notably, the filtered culture from LPS-lysed RBCs further promoted mo-DCs migration in a concentration dependent manner. From a therapeutic perspective, cyclic peptide inhibitor of integrin α4β1 combined with methylprednisolone (α4β1/Methrol) remarkably blocked RBCs aggregation to mo-DCs, HLMVEC, or mo-DCs and HLMVEC mixture. Moreover, α4β1/Methrol dramatically reduced mo-DCs migration up-regulated glucocorticoid-induced leucine zipper in mo-DCs, and ultimately reversed immune cell dysfunction induced by hemolysis. Taken together, these results indicate that integrin α4β1 on RBCs could mediate cell-cell interaction for adaptive immunity through influencing cell adhesion, migration, and T cell proliferation.

Hyperoside, a flavonol glycoside, is derived from plants of the genera Hypericum and Crataegus. Recent studies have indicated the anti-apoptotic and anti-inflammatory roles of hyperoside. The present study was designed to measure the effects of hyperoside on high glucose (HG)-treated HK-2 cells. HK-2 is a human papillomavirus 16 transformed cell line and can be used as a model for normal tubular cell. Cell apoptosis was examined by TUNEL assays and flow cytometry analysis. Inflammatory response was detected by Enzyme linked immunosorbent assay kits. Western blotting was applied to detect protein levels of apoptosis-related genes and inflammatory cytokines. Mechanistical assays including luciferase reporter and RNA pull down assays were applied to detect the binding relationship between molecules. We identified that hyperoside protected HK-2 cells against HG-induced apoptosis and inflammation. Moreover, miR-499a-5p was upregulated by hyperoside in a dose dependent manner. MiR-499a-5p inhibition rescued the suppressive effects of hyperoside on apoptosis and inflammation of HG-treated HK-2 cells. Furthermore, miR-499a-5p targeted NRIP1 to inhibit its mRNA expression, and further suppressed its translation. NRIP1 was downregulated by hyperoside in a dose dependent manner. Finally, rescue assays indicated that miR-499a-5p inhibition rescued the protective effects of hyperoside on apoptosis and inflammatory response of HK-2 cells by NRIP1. In conclusion, our findings revealed that hyperoside alleviates HG-induced apoptosis and inflammatory response of HK-2 cells by the miR-499a-5p/NRIP1 axis.

University libraries use social networks to promote reading; however, there are challenges to increasing the use of these library platforms, such as poor promotion and low reader participation. Therefore, these libraries need to find ways of dealing with the behavior characteristics of social network readers. In this study, a simulation experiment was developed to explore the behaviors of readers seeking book reviews and opinions on social networks. The study draws on social network theory to find the causes of students’ behavior and how these affect their selection of information. Finally, it presents strategies for peer reading promotion in university libraries.

Anti-programmed cell death protein 1 (PD-1) therapy has shown promising efficacy in hepatocellular carcinoma (HCC), but its response rates in advanced HCC are lower than 20%. A critical reason for this is the imbalance between CD8+ T cells and tumor burden. Here, a novel concept of vascular disruption and normalization dependent on a polymeric vascular disrupting agent (VDA) poly (L-glutamic acid)-graft-methoxy poly (ethylene glycol)/combretastatin A4 (CA4-NPs) + a vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) inhibitor DC101 is applied to improve anti-PD-1 therapy, wherein CA4-NPs reduce tumor burden and DC101 simultaneously increases the number of intratumoral CD8+ T cells, successfully regulating the abovementioned imbalance in an H22 tumor model. Methods: Blood vessel density, tumor cell proliferation, and necrosis were evaluated to reveal the effects on reducing tumor burden by CA4-NP treatment. Pericyte coverage of blood vessels, tumor blood vessel perfusion, tumor hypoxia, and intratumoral immune cells were examined to verify their role in vascular normalization and immune cell homing of DC101. Furthermore, the effects of CA4-NPs + DC101 on reducing tumor burden and increasing the number of immune cells were studied. Finally, tumor suppression, intratumoral CD8+ T cell activation, and the synergistic effects of anti-PD-1 combined with CA4-NPs + DC101 were verified. Results: The tumor inhibition rate of anti-PD-1 antibody combined with CA4-NPs + DC101 reached 86.4%, which was significantly higher than that of anti-PD-1 (16.8%) alone. Importantly, the Q value reflecting the synergy between CA4-NPs + DC101 and anti-PD-1 was 1.24, demonstrating a strong synergistic effect. Furthermore, CA4-NPs + DC101 improved anti-PD-1 therapy by increasing the number of intratumoral CD8+ T cells (anti-PD-1, 0.31% vs triple drug combination, 1.18%). Conclusion: These results reveal a novel approach to enhance anti-PD-1 therapy with VDAs + VEGF/VEGFR2 inhibitors in HCC.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a severe and rapidly evolving epidemic. Now, although a few drugs and vaccines have been proved for its treatment and prevention, little systematic comments are made to explain its susceptibility to humans. A few scattered studies used bioinformatics methods to explore the role of microRNA (miRNA) in COVID-19 infection. Combining these timely reports and previous studies about virus and miRNA, we comb through the available clues and seemingly make the perspective reasonable that the COVID-19 cleverly exploits the interplay between the small miRNA and other biomolecules to avoid being effectively recognized and attacked from host immune protection as well to deactivate functional genes that are crucial for immune system. In detail, SARS-CoV-2 can be regarded as a sponge to adsorb host immune-related miRNA, which forces host fall into dysfunction status of immune system. Besides, SARS-CoV-2 encodes its own miRNAs, which can enter host cell and are not perceived by the host’s immune system, subsequently targeting host function genes to cause illnesses. Therefore, this article presents a reasonable viewpoint that the miRNA-based interplays between the host and SARS-CoV-2 may be the primary cause that SARS-CoV-2 accesses and attacks the host cells.

MicroRNAs (miRNAs) participated in the regulation of tumorigenesis, progression, metastasis, recurrence and chemo-resistance of cancers. However, the potential function of miRNAs in cancer stem cells (CSCs) or tumor-initiating cells (T-ICs) was not clearly elucidated. In the present study, we found that miR-186 expression was reduced in liver CSCs. Functional studies showed that miR-186 knockdown facilitated liver CSCs self-renewal and tumorigenesis. Conversely, forced miR-186 expression suppressed liver CSCs self-renewal and tumorigenesis. Mechanically, miR-186 downregulated PTPN11 via binding to its 3’-UTR in liver CSCs. The correlation of miR-186 and PTPN11 was confirmed in Hepatocellular carcinoma (HCC) patients’ tissues. Further study showed that interference of PTPN11 can abolished the discrepancy between miR-186 mimic and control HCC cells in self-renewal and the proportion of CSCs. Additionally, we found that miR-186 overexpression HCC cells were more sensitive to cisplatin treatment. Clinical cohort analysis showed that HCC patients with high miR-186 were benefited more from transcatheter arterial chemoembolization (TACE) treatment. In conclusion, our study demonstrates a new regulation mechanism of liver CSCs, a new target for HCC, and a biomarker for postoperative TACE.

Hyperoside, a flavonol glycoside, is derived from plants of the genera Hypericum and Crataegus. Recent studies have indicated the anti-apoptotic and anti-inflammatory roles of hyperoside. The present study was designed to measure the effects of hyperoside on high glucose (HG)-treated HK-2 cells. HK-2 is a human papillomavirus 16 transformed cell line and can be used as a model for normal tubular cell. Cell apoptosis was examined by TUNEL assays and flow cytometry analysis. Inflammatory response was detected by Enzyme linked immunosorbent assay kits. Western blotting was applied to detect protein levels of apoptosis-related genes and inflammatory cytokines. Mechanistical assays including luciferase reporter and RNA pull down assays were applied to detect the binding relationship between molecules. We identified that hyperoside protected HK-2 cells against HG-induced apoptosis and inflammation. Moreover, miR-499a-5p was upregulated by hyperoside in a dose dependent manner. MiR-499a-5p inhibition rescued the suppressive effects of hyperoside on apoptosis and inflammation of HG-treated HK-2 cells. Furthermore, miR-499a-5p targeted NRIP1 to inhibit its mRNA expression, and further suppressed its translation. NRIP1 was downregulated by hyperoside in a dose dependent manner. Finally, rescue assays indicated that miR-499a-5p inhibition rescued the protective effects of hyperoside on apoptosis and inflammatory response of HK-2 cells by NRIP1. In conclusion, our findings revealed that hyperoside alleviates HG-induced apoptosis and inflammatory response of HK-2 cells by the miR-499a-5p/NRIP1 axis.

The solvent extraction, complexing ability, and basicity of tetradentate N-donor 2,9-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-1,10-phenanthroline (CyMe4-BT- Phen) and its derivatives functionalized by Br, hydroxyphenyl, nitryl were discussed and compared. It was demonstrated that four BTPhen ligands are able to selectively extract Am(lll) over Eu(lll). It was notable that the distribution ratio of 5-nitryl-CyMe4-BTPhen for Eu(lll) was suppressed under 0.02, which was much lower compared to DEu(lll) = 1 by CyMe4-BTPhen. The analysis of the effect of the substituent on the affinity to lanthanides was conducted by UV/vis and fluorescence spectroscopic titration. The stability constants of various ligands with Eu(lll) were obtained by fitting titration curve. Additionally, the basicity of various ligands was determined to be 3.1 ± 0.1, 2.3 ± 0.2, 0.9 ± 0.2, 0.5 ± 0.1 by NMR in the media of CD3OD with the addition of DClO4. The basicity of ligands follows the order of L1 > L2 > L3 > L4, indicating the tendency of protonation decreases with the electron-withdrawing ability increase.

Recent years have seen a rapid development of electronic skin for wearable devices, autonomous robotics, and human-machine interaction. As a result, the demand for flexible pressure sensors as the critical sensing element in electronic skin is also increasing. These sensors need to feature high sensitivity, short response time, low detection limit, and so on. In this paper, inspired from the cobweb in nature, we propose a piezoresistive pressure sensor by forming a cobweb-like network made of a zinc octaethylphorphyrin (ZnOEP)/carbon nanotube (CNT) hybrid on an array of polydimethylsiloxane (PDMS) microposts. The hybrid material exhibits excellent adhesion to PDMS, benefitting from ZnOEP's low Young's modulus and the nonpolar bonding between ZnOEP and PDMS such that no delamination and resistance variation are found after thousands of cycles of bending and twisting. With the overhanging morphology of the ZnOEP/CNT network on the micropost array, we realized a pressure sensor with an ultrahigh sensitivity of 39.4 kPa-1, a super-fast response time of 3 ms, a low detection limit of 10 Pa, and a reproducible response without degradation after 5000 cycles of pressure loading/unloading. The sensor can be employed for a variety of applications, including wrist pulse measurement, sound level detection, mechanical vibration monitoring, etc., proving its great potential for use in electronic skin systems.

Tumor vaccine inducing effective and perdurable antitumor immunity has a great potential for cancer prevention and therapy. The key indicator for a successful tumor vaccine is boosting the immune system to produce more memory T cells. Although many tumor vaccines have been designed, few of them involve in actively regulating immune memory CD8+T cells. Here a tumor vaccine vector (TA-Met@MS) by encapsulating tumor antigen (TA), metformin (Met) and Hollow gold nanospheres (HAuNS) into poly (lactic-co-glycolic acid) (PLGA) microspheres was presented. TA via the treatment of photothermal therapy (PTT) showed high immunogenicity and immune-adjuvant effectiveness. And NIR light-mediated photothermal effect can lead to a pulsed-release behavior of TA and Met from the microspheres. The released TA can regulate primary T cell expansion and contraction, and stimulate the production of effector T cells at the early immunization stage. The metabolic behavior of the cells is then intervened from glycolysis into fatty acids oxidation (FAO) through the activation of AMPK mediated by Met, which can enhance T cell survival and facilitate the differentiation of memory CD8+T cells. This study may present a valuable insight to design tumor vaccine for enhanced cancer prevention and therapy.

The rejuvenation of Zr52.5Cu17.9Ni14.6Al10Ti5 bulk metallic glasses (BMGs) by ultrasonic vibration-assisted elastic deformation (UVEF) was studied herein. The UVEF-treated samples demonstrate an obvious rejuvenation and have a higher relaxation enthalpy and a smaller range of supercooled liquid regions than the as-cast samples. The fracture of the rejuvenated amorphous alloy is mainly ductile fracture, and shear deformation occurs in the deformation region. It is also found that as the amplitude increases, the free volume of the rejuvenated amorphous alloy increases, the yield strength and the elastic modulus decrease, and the formability increases. The free-volume content is used to characterize the degree of rejuvenation, and a mathematical model of the relationship between the ultrasonic amplitude and free volume is established. In addition, it is found that the ultrasonic vibration stress induces the additional free volume in the Zr-based bulk metallic glasses and improves the plasticizing behavior. The temperature rise caused by the ultrasonic thermal effect does not induce additional free volume.

RRM2, the small subunit of ribonucleotide reductase, is identified as a tumor promotor and therapeutic target. It is common to see the overexpression of RRM2 in chemo-resistant cancer cells and patients. RRM2 mediates the resistance of many chemotherapeutic drugs and could become the predictor for chemosensitivity and prognosis. Therefore, inhibition of RRM2 may be an effective means to enhance the anticancer activity of chemotherapy. This review tries to discuss the mechanisms of RRM2 overexpression and the role of RRM2 in resistance to chemotherapy. Additionally, we compile the studies on small interfering RNA targets RRM2, RRM2 inhibitors, kinase inhibitors, and other ways that could overcome the resistance of chemotherapy or exert synergistic anticancer activity with chemotherapy through the expression inhibition or the enzyme inactivation of RRM2.

The system constructs a virtual digital model of knee joint and makes full use of virtual reality technology to interpret and visualize it. All anatomical structures of the knee joint can be displayed comprehensively and clearly, so that students can understand the examination and surgical treatment of knee joint injuries. The system is equipped with different teaching links including simulation demonstration, autonomous learning, repeated training, intelligent evaluation, etc. It can endow students a relaxed and fast learning experience and stimulate students' learning interest and autonomous learning ability.Visualization of medical data, dynamic tissue model in knee joint cavity, stress deformation simulation of knee joint tissues and organs, demonstration of simulated minimally invasive surgery cases.

Constructing regular micro-structures with certain geometric characteristics on the surface of the polymer part can obtain some specific functions. Micro ultrasonic powder molding (micro-UPM) is an efficient processing technique for the fabrication of well-filled micro-structured Polypropylene (PP) parts. The micro-structure array on the surface of the core insert was obtained by low speed wire electrical discharge machining (WEDM-LS). PP polymer surfaces with micro-structured patterns were successfully replicated from the core insert surface after micro-UPM. By studying the detailed topography characterizations of micro-structured PP parts, the effects of processing parameters (ultrasonic energy, welding pressure and holding time) on the micro-structured filling show that when PP polymer was formed under the conditions of 1000 J, 115 kPa and 8 s during micro-UPM, well-filled micro-structured parts can be obtained. Besides, without low surface energy coating modification, the water contact angles (WCAs) of micro-structured PP parts increased from 85.3&deg, to 146.8&deg, indicating that the wettability of the surface can be changed by replicating the micro-structure on PP parts after micro-UPM.

A new sintering method, namely ultrasonic assisted sintering (UAS), has been proposed using mechanical heat converted from high frequency motion between particles. Pure aluminum specimens with diameter of 5 mm and thickness of ~2 mm have been successfully sintered in two seconds. Based on the thermodynamic analysis, the underlying heating mechanism is quantitatively interpreted, which involves high-frequency interparticle friction and plastic deformation driven by ultrasonic squeezing. Consequently, temperature rises rapidly at a speed of about 300 K/s, and the maximum temperature reaches up to 0.9 times of melting point of the aluminum during UAS. The sintered specimens have a high density of dislocations, under the combined effects of dislocations and undulating stress field, volume diffusion coefficient for sintering increases by several orders of magnitude, therefore, rapid densification can be accomplished in seconds. In addition, the sintered aluminum has ultrahigh nanohardness (~1.13 GPa), which can be attributed to the hierarchical structure formed during UAS process.

To investigate the clinical and pathological characteristics of lupus nephritis (LN) patients with serositis and analyse the relationship between serositis and hyperuricemia (HUA) in LN patients in northeast China. The data of patients with LN diagnosed by renal biopsy in our hospital from April 2013 to May 2020 were retrospectively analyzed. The differences between the non-serositis and serositis groups were compared by t tests and Chi-square test. Factors with P

Stenting for iliac vein stenosis or compression has become a common therapeutic approach in recent years. The antithrombotic therapy after the stent deployment, however, reaches no consensus. Medications strategies and patients' prognoses differ in non-thrombotic, acute thrombotic and chronic thrombotic these three circumstances. Non-thrombotic patients usually possess satisfactory stent patency whatever antithrombotic therapy is used. Anticoagulant is the basic medication for acute thrombotic patients, benefits from additional antiplatelet drug remains to be clarified. In terms of chronic thrombotic patients, their prognoses are unsatisfactory under all antithrombotic therapies. In this review, we outlined the recent progress of antithrombotic therapy after iliac vein stenting, aiming to provide feasible medication plans for each circumstance.