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Abstract Alphaviruses are arboviruses transmitted by mosquitoes and are pathogenic to humans and livestock, causing a substantial public health burden. So far, several receptors have been identified for alphavirus entry; however, they cannot explain the broad host range and tissue tropism of certain alphaviruses, such as Getah virus (GETV), indicating the existence of additional receptors. Here we identify the evolutionarily conserved low-density lipoprotein receptor (LDLR) as a new cell entry factor for GETV, Semliki Forest virus (SFV), Ross River virus (RRV) and Bebaru virus (BEBV). Ectopic expression of LDLR facilitates cellular binding and internalization of GETV, which is mediated by the interaction between the E2-E1 spike of GETV and the ligand-binding domain (LBD) of LDLR. Antibodies against LBD block GETV infection in cultured cells. In addition, the GST-LBD fusion protein inhibits GETV infection both in vitro and in vivo. Notably, we identify the key amino acids in LDLR-LBD that played a crucial role in viral entry; specific mutations in the CR4 and CR5 domain of LDLR-LBD reduce viral entry to cells by more than 20-fold. These findings suggest that targeting the LDLR-LBD could be a potential strategy for the development of antivirals against multiple alphaviruses.

Abstract Robust hydrogels offer a candidate for artificial skin of bionic robots, yet few hydrogels have a comprehensive performance comparable to real human skin. Here, we present a general method to convert traditional elastomers into tough hydrogels via a unique radiation-induced penetrating polymerization method. The hydrogel is composed of the original hydrophobic crosslinking network from elastomers and grafted hydrophilic chains, which act as elastic collagen fibers and water-rich substances. Therefore, it successfully combines the advantages of both elastomers and hydrogels and provides similar Young’s modulus and friction coefficients to human skin, as well as better compression and puncture load capacities than double network and polyampholyte hydrogels. Additionally, responsive abilities can be introduced during the preparation process, granting the hybrid hydrogels shape adaptability. With these unique properties, the hybrid hydrogel can be a candidate for artificial skin, fluid flow controller, wound dressing layer and many other bionic application scenarios.

Abstract Time-resolved identification of surface-bound intermediates on metallic nanocatalysts is imperative to develop an accurate understanding of the elementary steps of CO2 reduction. Direct observation on initial electron transfer to CO2 to form surface-bound CO2 •− radicals is lacking due to the technical challenges. Here, we use picosecond pulse radiolysis to generate CO2 • − via aqueous electron attachment and observe the stabilization processes toward well-defined nanoscale metallic sites. The time-resolved method combined with molecular simulations identifies surface-bound intermediates with characteristic transient absorption bands and distinct kinetics from nanosecond to the second timescale for three typical metallic nanocatalysts: Cu, Au, and Ni. The interfacial interactions are further investigated by varying the important factors, such as catalyst size and the presence of cation in the electrolyte. This work highlights fundamental ultrafast spectroscopy to clarify the critical initial step in the CO2 catalytic reduction mechanism.

Brucellosis is a zoonotic infectious disease that has long endangered the development of animal husbandry and human health. Currently, vaccination stands as the most efficacious method for preventing and managing brucellosis. Alum, as the most commonly used adjuvant for the brucellosis vaccine, has obvious disadvantages, such as the formation of granulomas and its non-degradability. Therefore, the aims of this study were to prepare an absorbable, injectable, and biocompatible hydroxypropyl chitin (HPCT) thermosensitive hydrogel and to evaluate its immunization efficacy as an adjuvant for Brucella antigens. Specifically, etherification modification of marine natural polysaccharide chitin was carried out to obtain a hydroxypropyl chitin. Rheological studies demonstrated the reversible temperature sensitivity of HPCT hydrogel. Notably, 5 mg/mL of bovine serum albumin can be loaded in HPCT hydrogels and released continuously for more than one week. Furthermore, the L929 cytotoxicity test and in vivo degradation test in rats proved that an HPCT hydrogel had good cytocompatibility and histocompatibility and can be degraded and absorbed in vivo. In mouse functional experiments, as adjuvants for Brucella antigens, an HPCT hydrogel showed better specific antibody expression levels and cytokine (Interleukin-4, Interferon-γ) expression levels than alum. Thus, we believe that HPCT hydrogels hold much promise in the development of adjuvants.

Abstract The efficient use of renewable X/γ-rays or accelerated electrons for chemical transformation of CO2 and water to fuels holds promise for a carbon-neutral economy; however, such processes are challenging to implement and require the assistance of catalysts capable of sensitizing secondary electron scattering and providing active metal sites to bind intermediates. Here we show atomic Cu-Ni dual-metal sites embedded in a metal-organic framework enable efficient and selective CH3OH production (~98%) over multiple irradiated cycles. The usage of practical electron-beam irradiation (200 keV; 40 kGy min−1) with a cost-effective hydroxyl radical scavenger promotes CH3OH production rate to 0.27 mmol g−1 min−1. Moreover, time-resolved experiments with calculations reveal the direct generation of CO2 •‒ radical anions via aqueous electrons attachment occurred on nanosecond timescale, and cascade hydrogenation steps. Our study highlights a radiolytic route to produce CH3OH with CO2 feedstock and introduces a desirable atomic structure to improve performance.

Postmenopausal osteoporosis is the most common type of osteoporosis. Chondroitin sulfate (CS) has been successfully employed as food supplement against osteoarthritis, while the therapeutic potential on postmenopausal osteoporosis is little explored. In this study, CS oligosaccharides (CSOs) were enzymatically prepared through the lysis of CS by a chondroitinase from Microbacterium sp. Strain. The alleviating effects of CS, CSOs and Caltrate D (a clinically used supplement) on ovariectomy (OVX) ‐ induced rat’s osteoporosis were comparatively investigated. Our data showed that the prepared CSOs was basically unsaturated CS disaccharide mixture of ∆Di4S (53.1%), ∆Di6S (27.7%) and ∆Di0S (17.7%). 12 weeks’ intragastric administration of Caltrate D (250 mg/kg/d), CS or CSOs (500 mg/kg/d, 250 mg/kg/d, 125 mg/kg/d) could obviously regulate the disorder of serum indices, recover the mechanical strength and mineral content of bone, improve the cortical bones’ density and the number and length of trabecular bones in OVX rats. Both CS and CSOs in 500 mg/kg/d and 250 mg/kg/d could restore more efficiently the serum indices, bone fracture deflection and femur Ca than Caltrate D. As compared with CS at the same dosage, CSOs exhibited a more significant alleviating effect. These findings suggested that there was great potential of CSOs as daily interventions for delaying the progression of postmenopausal osteoporosis.

BackgroundBladder cancer is the ninth most common malignant tumor worldwide. As an effective evidence-based multidisciplinary protocol, the enhanced recovery after surgery (ERAS) program is practiced in many surgical disciplines. However, the function of ERAS after radical cystectomy remains controversial. This systematic review and meta-analysis aims to research the impact of ERAS on radical cystectomy.MethodsA systematic literature search on PubMed, EMBASE, SCOPUS, and the Cochrane Library databases was conducted in April 2022 to identify the studies that performed the ERAS program in radical cystectomy. Studies were selected, data extraction was performed independently by two reviewers, and quality was assessed using a random effects model to calculate the overall effect size. The odds ratio and standardized mean difference (SMD) with a 95% confidence interval (CI) served as the summary statistics for the meta-analysis. A sensitivity analysis was subsequently performed.ResultsA total of 25 studies with 4,083 patients were enrolled. The meta-analysis showed that the complications (OR = 0.76; 95% CI: 0.63–0.90), transfusion rate (OR = 0.59; 95% CI: 0.39–0.90), readmission rate (OR = 0.79; 95% CI: 0.64–0.96), length of stay (SMD = −0.79; 95% CI: −1.41 to −0.17), and time to first flatus (SMD = −1.16; 95% CI: −1.58 to −0.74) were significantly reduced in the ERAS group. However, no significance was found in 90-day mortality and urine leakage.ConclusionThe ERAS program for radical cystectomy can effectively decrease the risk of overall complications, postoperative ileus, readmission rate, transfusion rate, length of stay, and time to first flatus in patients who underwent radical cystectomy with relative safety.Systematic Review Registrationhttps://inplasy.com/, identifier INPLASY202250075.

The application of fertilizer is necessary for the growth and yield of crops, especially for paddy rice. Precision application is important for the fertilizer utilization rate and sustainable development of agriculture. However, the crushing of fertilizer grains will reduce the quality of fertilization, for the decrease in the size and mass of the fertilizer particles and the degree of crushing mainly depend on the physical and mechanical properties of the fertilizer grains. In this study, the compression strength and critical impact speed of four typical commonly used fertilizer grains, a compound fertilizer of nitrogen, phosphorus, and potassium (NPK compound fertilizer), organic fertilizer, large granular urea, and small granular urea, were measured and analyzed. The static compression test was carried out using a TMS-Pro texture analyzer and the results show that the four kinds of fertilizer grains are brittle materials, and their elastic moduli are 208 MPa, 233 MPa, 140 MPa, and 107 MPa, respectively; the theoretical impact model of fertilizer granules is established based on the compression test result and Hertz elastic contact theory, the theoretical formula for the critical impact speed of fertilizer grains is derived, and the theoretical critical impact strength and speed are worked out. An image capture system for the impact process of fertilizer grains was developed, and the impact test was conducted. The results show that the critical impact speed of the four kinds of fertilizer grains decreases with the increase in granule size, while the variance analysis shows that the effect is not significant. The comparison of the experimental results with the theoretical values shows that the theoretical formula could be used to predict the trends of the critical impact speed of fertilizer grains. The model was optimized with the MATLAB 2018 function fitting tool based on the test and analysis. The goodness of fit of the formula is 0.824, which is 13.43% greater than that of the original theoretical formula, indicating that the modified formula based on the compression test data might estimate the critical impact speed of the granular fertilizer with brittle material properties more accurately. The results may provide a reference for the parameter design of a precision fertilization machine.

Abstract Background Arterioureteral fistula (AUF) is a rare, life-threatening condition wherein communication occurs between a ureter and the common, internal, or external iliac artery. The sensitivity of common clinical imaging examination for AUF is low, which leads to a delayed diagnosis and increased mortality. In addition, the increased use of ureteral stents contributes to the growing frequency of AUF. Case presentation Our two patients were 74 and 65 years old males respectively. They both had a medical history of bladder cancer and underwent radical cystectomy with ureterocutaneostomy. The patients underwent routine catheter exchange during over 1 year postradical cystectomy and subsequently experienced intermittent gross pulsatile haematuria. After a series of imaging examinations failed to identify the cause, the patients were ultimately diagnosed with AUF and treated with interventional radiotherapy, followed by broad-spectrum antibiotics. Positive effects were found. Conclusions The incidence of AUF is increased with the prolongation of survival in patients with related risk factors. This case report aims to highlight early diagnosis and management of AUF to lower the mortality.

BackgroundIncreased rates of methicillin-resistant Staphylococcus aureus (MRSA) antibiotic resistance and the associated morbidity have increased dermatologists' attention to skin and soft tissue MRSA infections. However, the clinical characterization of MRSA skin and soft tissue infections (SSTIs) in Southwest China is lacking, which precludes optimal prevention and treatment of these infections.ObjectivesThis study was conducted to characterize the prevalence, clinical comorbidities and antibiotic susceptibility of MRSA isolates from SSTIs, including community-associated (CA) and healthcare-associated (HA) isolates.MethodsIn the Dermatology Inpatient Department of the First Affiliated Hospital of Guangxi Medical University, a retrospective study was conducted on data, including patient demographics and clinical information, from culture-confirmed S. aureus isolated from skin and soft tissue between January 1, 2015, and December 31, 2021. Isolate susceptibility to 13 antibiotics was determined using the Vitek 2 system.ResultsFrom among 864 S. aureus strains, we identified 283 MRSA (32.75%) isolates comprising 203 CA-MRSA and 80 HA-MRSA isolates. The average rate of CA-MRSA isolation for MRSA SSTIs was 71.73%. The HA-MRSA isolation rate for MRSA SSTIs increased significantly. HA-MRSA-infected patients were older. The most common dermatological presentation of CA-MRSA infection was staphylococcal scalded skin syndrome, while the comorbidity severe drug eruption was significantly associated with HA-MRSA infection. One CA-MRSA strain was resistant to linezolid, and one HA-MRSA strain had an intermediate phenotype for vancomycin; both strains had low sensitivity to clindamycin and erythromycin (3.70%~19.40%). However, HA-MRSA isolates were more susceptible to trimethoprim/sulfamethoxazole.ConclusionsCA-MRSA is a predominant pathogen causing SSTIs, and HA-MRSA infection incidence is increasing gradually. Both strains showed increasing antibiotic resistance. Our data on MRSA susceptibility may guide dermatologist antibiotic treatment decisions. Dermatologists should consider these identified comorbidities of MRSA SSTIs when patients are admitted and initiate early prevention and treatment of MRSA.

Abstract Background Pigeon circovirus (PiCV) infections in pigeons (Columba livia) have been reported worldwide. Currently, pigeon racing is becoming increasingly popular and considered to be a national sport in China, and even, the greatest competitions of racing pigeons are taking place in China. However, there are still no epidemiologic data regarding PiCV infections among racing pigeons in China. The purpose of our study was to provide information of prevalence, genetic variation and evolution of PiCV from racing pigeons in China. Results To trace the prevalence, genetic variation and evolution of PiCV in sick and healthy racing pigeons, 622 samples were collected from 11 provinces or municipalities in China from 2016 to 2019. The results showed that the positive rate of PiCV was 19.3% (120/622) at the sample level and 59.0% (23/39) at the club level, thus suggesting that the virus was prevalent in Chinese racing pigeons. A sequence analysis revealed that the cap genes of the PiCV strains identified in our study displayed a high genetic diversity and shared nucleotide homologies of 71.9%–100% and amino acid homologies of 71.7%–100%. 28 and 36 unique amino acid substitutions were observed in the Cap and Rep proteins derived from our PiCV strains, respectively. A cladogram representation of PiCV strains phylogeny based on 90 cap gene sequences showed that the strains in this study could be further divided into seven clades (A, B, C, E, G, H, and I) and some of them were closely related to worldwide strains from different types of pigeons. A large number of recombination events (31 events) were also detected in the PiCV genomes from Chinese racing pigeons. Conclusions These findings indicate that PiCV strains circulating in China exhibit a high genetic diversity and also contribute to information of prevalence, genetic variation and evolution of PiCV from racing pigeons in China.

In recent years, carbon nanotubes(CNTs) have begun to attract attention in the fields of field emission, nanoelectronic devices, nano machines and composite reinforced materials. But the traditional processing methods for cutting these increase tool wear. However, non-traditional processing can be used to machine materials of any hardness and strength. In this paper, the research trends of non-traditional processing of CNTs are critically reviewed. First, this study introduces the application of CNTs and their development history. Second, the surface morphology, purification and growth effects of laser-processed CNTs are summarised, these are analysed and discussed. Subsequently, the effects of ultrasonic parameters and other external parameters on the diormance of ultrasonically processed CNTs are analysed. Next, the effects of electrical and non-electrical parameters on the surface morphology of CNTs processed by micro-electro-discharge machining(μEDM) are compared, and a summary analysis is presented. In addition, the research on the improvement of the performance of CNTs by electrochemical machining(ECM) is reviewed and prospected. Simultaneously, different non-traditional processing of CNTs is discussed. Finally, the most recent progress in non-traditional processing of CNTs is described, and the future trends, which may potentially guide subsequent research studies, are predicted.

In recent years, with the rapid development of artificial intelligence, machine vision technology has been widely used in various fields. Traditional cancer detection methods are time-consuming, labor-intensive, and highly dependent on the experience of pathologists; therefore, these methods cannot meet the needs of modern medical treatment. Machine vision overcomes the disadvantages of traditional detection methods in cancer detection and can help pathologists improve the detection accuracy. According to the requirements of medical detection, this review summarizes the applications of machine vision in the detection of cancer cells in histopathological images and analyzes the advantages and disadvantages of existing methods in image preprocessing, segmentation, feature extraction and recognition. Finally, research on the detection methods of histopathological cancer cells is reviewed and prospected, and future development trends are predicted to provide guidance for follow-up research.

Background Next-generation cancer immunotherapies are designed to broaden the therapeutic repertoire by targeting new immune checkpoints including lymphocyte-activation gene 3 (LAG-3) and T cell immunoglobulin and mucin-domain containing-3 (TIM-3). Yet, the molecular and cellular mechanisms by which either receptor functions to mediate its inhibitory effects are still poorly understood. Similarly, little is known on the differential effects of dual, compared with single, checkpoint inhibition.Methods We here performed in-depth characterization, including multicolor flow cytometry, single cell RNA sequencing and multiplex supernatant analysis, using tumor single cell suspensions from patients with cancer treated ex vivo with novel bispecific antibodies targeting programmed cell death protein 1 (PD-1) and TIM-3 (PD1-TIM3), PD-1 and LAG-3 (PD1-LAG3), or with anti-PD-1.Results We identified patient samples which were responsive to PD1-TIM3, PD1-LAG3 or anti-PD-1 using an in vitro approach, validated by the analysis of 659 soluble proteins and enrichment for an anti-PD-1 responder signature. We found increased abundance of an activated (HLA-DR+CD25+GranzymeB+) CD8+ T cell subset and of proliferating CD8+ T cells, in response to bispecific antibody or anti-PD-1 treatment. Bispecific antibodies, but not anti-PD-1, significantly increased the abundance of a proliferating natural killer cell subset, which exhibited enrichment for a tissue-residency signature. Key phenotypic and transcriptional changes occurred in a PD-1+CXCL13+CD4+ T cell subset, in response to all treatments, including increased interleukin-17 secretion and signaling toward plasma cells. Interestingly, LAG-3 protein upregulation was detected as a unique pharmacodynamic effect mediated by PD1-LAG3, but not by PD1-TIM3 or anti-PD-1.Conclusions Our in vitro system reliably assessed responses to bispecific antibodies co-targeting PD-1 together with LAG-3 or TIM-3 using patients’ tumor infiltrating immune cells and revealed transcriptional and phenotypic imprinting by bispecific antibody formats currently tested in early clinical trials.

In recent years, the environmental problems accompanying the extensive application of biomedical polymer materials produced from fossil fuels have attracted more and more attentions. As many biomedical polymer products are disposable, their life cycle is relatively short. Most of the used or overdue biomedical polymer products need to be burned after destruction, which increases the emission of carbon dioxide (CO2). Developing biomedical products based on CO2 fixation derived polymers with reproducible sources, and gradually replacing their unsustainable fossil-based counterparts, will promote the recycling of CO2 in this field and do good to control the greenhouse effect. Unfortunately, most of the existing polymer materials from renewable raw materials have some property shortages, which make them unable to meet the gradually improved quality and property requirements of biomedical products. In order to overcome these shortages, much time and effort has been dedicated to applying nanotechnology in this field. The present paper reviews recent advances in nanocomposites of CO2 fixation derived reproducible polymers for biomedical applications, and several promising strategies for further research directions in this field are highlighted.

The high variability and unpredictability of the plasma concentration of voriconazole (VRC) pose a major challenge for clinical administration. The aim of this study was to develop a population pharmacokinetics (PPK) model of VRC and identify the factors influencing VRC PPK in patients with talaromycosis. Medical records and VRC medication history of patients with talaromycosis who were treated with VRC as initial therapy were collected. A total of 233 blood samples from 69 patients were included in the study. A PPK model was developed using the nonlinear mixed-effects models (NONMEM). Monte Carlo simulation was applied to optimize the initial dosage regimens with a therapeutic range of 1.0–5.5 mg/L as the target plasma trough concentration. A one-compartment model with first-order absorption and elimination adequately described the data. The typical voriconazole clearance was 4.34 L/h, the volume of distribution was 97.4 L, the absorption rate constant was set at 1.1 h-1, and the bioavailability was 95.1%. Clearance was found to be significantly associated with C-reactive protein (CRP). CYP2C19 polymorphisms had no effect on voriconazole pharmacokinetic parameters. ‏Monte Carlo simulation based on CRP levels showed that a loading dose of 250 mg/12 h and a maintenance dose of 100 mg/12 h are recommended for patients with CRP ≤ 96 mg/L, whereas a loading dose of 200 mg/12 h and a maintenance dose of 75 mg/12 h are recommended for patients with CRP > 96 mg/L. The average probability of target attainment of the optimal dosage regimen in CRP ≤ 96 mg/L and CRP > 96 mg/L groups were 61.3% and 13.6% higher than with empirical medication, and the proportion of Cmin > 5.5 mg/L decreased by 28.9%. In conclusion, the VRC PPK model for talaromycosis patients shows good robustness and predictive performance, which can provide a reference for the clinical individualization of VRC. Adjusting initial dosage regimens based on CRP may promote the rational use of VRC.

Bone defects, a common orthopedic problem in clinical practice, are a serious threat to human health. As alternative materials to autologous bone grafts, synthetic cell-free functionalized scaffolds have been the focus of recent research in designing scaffolds for bone tissue engineering. Butyryl chitin (BC) is a derivative of chitin (CT) with improved solubility. It has good biocompatibility, but few studies have investigated its use in bone repair. In this study, BC was successfully synthesized with a degree of substitution of 2.1. BC films were prepared using the cast film method and showed strong tensile strength (47.8 ± 4.54 N) and hydrophobicity (86.4 ± 2.46°), which was favorable for mineral deposition. An in vitro cytological assay confirmed the excellent cell attachment and cytocompatibility of the BC film; meanwhile, in vivo degradation indicated the good biocompatibility of BC. Hydroxyapatite (HA), extracted from bovine cancellous bone, had good cytocompatibility and osteogenic induction activity for the mouse osteoblast cell line MC3T3-E1. With the aim of combining the advantages of BC and HA, a BC–HA composite scaffold, with a good pore structure and mechanical strength, was prepared by physical mixing. Administered into skull defects of rats, the scaffolds showed perfect bone-binding performance and effective structural support, and significantly promoted the regeneration of new bone. These results prove that the BC–HA porous scaffold is a successful bone tissue engineering scaffold and has strong potential to be further developed as a substitute for bone transplantation.

Data processing is an essential component of heavy-metal ion detection. Most of the research now uses a conventional data-processing approach, which is inefficient and time-consuming. The development of an efficient and accurate automatic measurement method for heavy-metal ions has practical implications. This paper proposes a CNN-based heavy-metal ion detection system, which can automatically, accurately, and efficiently detect the type and concentration of heavy-metal ions. First, we used square-wave voltammetry to collect data from heavy-metal ion solutions. For this purpose, a portable electrochemical constant potential instrument was designed for data acquisition. Next, a dataset of 1200 samples was created after data preprocessing and data expansion. Finally, we designed a CNN-based detection network, called HMID-NET. HMID-NET consists of a backbone and two branch networks that simultaneously detect the type and concentration of the ions in the solution. The results of the assay on 12 sets of solutions with different ionic species and concentrations showed that the proposed HMID-NET algorithm ultimately obtained a classification accuracy of 99.99% and a mean relative error of 8.85% in terms of the concentration.

Based on the rapid development of semiconductors, integrated circuits and the Internet. 3C products such as computers, tablets, mobile phones and smart TVs have become an indispensable part of people’s lives. With the prosperity and development of the 3C product market, the demand for the quality of display panels and related detection technologies are increasing. As the iconic network of deep learning, has been extensively studied in the field of image recognition and defect detection. Based on the development of CNN, this article summarizes the defect detection method of 3C products by CNN with different depths. First, we reviewed the origin of CNN and its structural components, then introduced the upgrade and improvement of important components, and finally introduced and compared the applications of CNN with different depths in defect detection. Through the comparison and summary of the effect of defect detection, we analyze the opportunities and challenges of different CNN frameworks, and exhibit the strategies for different application scenarios.

Increasing evidence has elucidated that the microbiome plays a critical role in many human diseases. Apart from continuous and binary traits that measure the extent or presence of a disease, multi-categorical outcomes including variations/subtypes of a disease or ordinal levels of disease severity are commonly seen in clinical studies. On top of that, studies with clustered design (i.e., family-based and longitudinal studies) are popular alternatives to population-based ones as they are able to identify characteristics on both individual and population levels and to investigate the trajectory of traits of interest over time. However, existing methods for microbiome association analysis are inadequate to handle multi-categorical outcomes, neither independent nor clustered data. We propose a microbiome kernel association test with multi-categorical outcomes (MiRKAT-MC). Our method is versatile to deal with both nominal and ordinal outcomes for independent and clustered data. In addition, it incorporates multiple ecological distances to allow for different association patterns between outcomes and microbiome compositions to be incorporated. A computationally efficient pseudo-permutation strategy is used to evaluate the statistical significance. Comprehensive simulations show that MiRKAT-MC preserves the nominal type I error and increases statistical powers under various scenarios and data types. We also apply MiRKAT-MC to real data sets with nominal and ordinal outcomes to gain biological insights. MiRKAT-MC is easy to implement, and freely available via an R package at https://github.com/Zhiwen-Owen-Jiang/MiRKATMC with a Graphical User Interface through R Shinny also available.

A three-DOF (degree-of-freedom) serial-parallel hybrid mechanism is proposed that consists of a 2-UPS+U component (UPS: universal-/prismatic-/spherical-joint chain and U: universal joint) and an R+RPS component (R: revolute joint and RPS: revolute-/prismatic-/spherical-joint chain). This mechanism can provide high precision and a large workspace, which indicates its applicability to wheel-legged robots. To verify our proposal, a mobility analysis showed that the mechanism simultaneously achieved three rotational movements. Then, the inverse/forward position analysis, velocity analysis, acceleration analysis, and stiffness analysis were carried out. Finally, a prototype of the mechanism was fabricated and its position error was found to be

To combat climate change and meet energy conservation and emission reduction goals, the building sector must adopt low-carbon technologies and low-carbon management methods. To systematically explore existing research areas and track future research trends of carbon emission in the construction stage (CECS), this study conducts a bibliometric and content analysis of CECS studies. 563 relevant publications published between 2000 and 2022 are examined and analyzed using data from the Web of Science (WoS) core collection database. The findings reveal that studies of CECS have evolved through three stages: preliminary exploratory period, stable development period, and rapid development period. In addition, the literature co-citation network and content analysis classify the 13 found co-citation clusters into four knowledge domains: sources definition, data statistics, assessment methods, and carbon reduction strategies. Finally, a knowledge map of CECS studies is presented, outlining significant aspects of research, existing gaps in knowledge, and directions for future study. This work will make it easier for academics and professionals to pinpoint promising areas of study, fill in knowledge gaps, and broaden the scope of existing research on CECS.

Abstract Background Radiation sensitive 52 (RAD52) is an important protein that mediates DNA repair in tumors. However, little is known about the impact of RAD52 on hepatocellular carcinoma (HCC). We investigated the expression of RAD52 and its values in HCC. Some proteins that might be coordinated with RAD52 in HCC were also analyzed. Methods Global RAD52 mRNA levels in HCC were assessed using The Cancer Genome Atlas (TCGA) database. RAD52 expression was analyzed in 70 HCC tissues and adjacent tissues by quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemistry. The effect of over-expressed RAD52 in Huh7 HCC cells was investigated. The String database was then used to perform enrichment and functional analysis of RAD52 and its interactome. Cytoscape software was used to create a protein–protein interaction network. Molecular interaction studies with RAD52 and its interactome were performed using the molecular docking tools in Hex8.0.0. Finally, these DNA repair proteins, which interact with RAD52, were also analyzed using the TCGA dataset and were detected by qRT-PCR. Based on the TCGA database, algorithms combining ROC between RAD52 and RAD52 interactors were used to diagnose HCC by binary logistic regression. Results In TCGA, upregulated RAD52 related to gender was obtained in HCC. The area under the receiver operating characteristic curve (AUC) of RAD52 was 0.704. The results of overall survival (OS) and recurrence-free survival (RFS) indicated no difference in the prognosis between patients with high and low RAD52 gene expression. We validated that RAD52 expression was increased at the mRNA and protein levels in Chinese HCC tissues compared with adjacent tissues. Higher RAD52 was associated with older age, without correlation with other clinicopathological factors. In vitro, over-expressed RAD52 significantly promoted the proliferation and migration of Huh7 cells. Furthermore, RAD52 interactors (radiation sensitive 51, RAD51; X-ray repair cross complementing 6, XRCC6; Cofilin, CFL1) were also increased in HCC and participated in some biological processes with RAD52. Protein structure analysis showed that RAD52–RAD51 had the firmest binding structure with the lowest E-total energy (− 1120.5 kcal/mol) among the RAD52–RAD51, RAD52–CFL1, and RAD52–XRCC6 complexes. An algorithm combining ROC between RAD52 and its interactome indicated a greater specificity and sensitivity for HCC screening. Conclusions Overall, our study suggested that RAD52 plays a vital role in HCC pathogenesis and serves as a potential molecular target for HCC diagnosis and treatment. This study’s findings regarding the multigene prediction and diagnosis of HCC are valuable.

Chitosan (CTS) has been used as a nerve guidance conduit (NGC) material for bridging peripheral nerve defects due to its biocompatible, biodegradable, and non-toxic properties. However, the nerve regeneration effect of chitosan alone is restricted due to its inadequate biological activity. Herein, a composite, bioactive chitosan based nerve conduit, consisting of outer warp-knitted tube scaffold made from medical-grade chitosan fiber, and inner porous cross linked carboxymethyl chitosan (C-CM-CTS) sponge with radial texture was developed. The inner wall of the scaffold was coated with C-CM-CTS solution. CM-CTS provided favorable bioactivities in the composite chitosan-based nerve conduit. An in vitro study of CM-CTS revealed its satisfying biocompatibility with fibroblast and its inhibition of oxidative damage to Schwann cells. As the internal filler of the NGC, the lyophilized sponge of C-CM-CTS showed a longitudinal guidance effect for nerve reconstruction. After 10 mm defect in rat sciatic nerve was bridged with the composite bioactive chitosan-based nerve conduit, the nerve conduit was able to effectively promote axonal regeneration and played a positive role in inducing nerve regeneration and functional recovery. In addition to the functional advantages, which are equal to those of an autograft; the technology for the preparation of this conduit can be put into mass production.

Because of their small size and large specific surface area, nanoparticles (NPs) have special properties that are different from bulk materials. In particular, Au/Ag NPs have been intensively studied for a long time, especially for biomedical applications. Thereafter, they played a significant role in the fields of biology, medical testing, optical imaging, energy and catalysis, MRI contrast agents, tumor diagnosis and treatment, environmental protection, and so on. When synthesizing Au/Ag NPs, the laser ablation and biosynthesis methods are very promising green processes. Therefore, this review focuses on the progress in the laser ablation and biological synthesis processes for Au/Ag NP generation, especially in their fabrication fundamentals and potential applications. First, the fundamentals of the laser ablation method are critically reviewed, including the laser ablation mechanism for Au/Ag NPs and the controlling of their size and shape during fabrication using laser ablation. Second, the fundamentals of the biological method are comprehensively discussed, involving the synthesis principle and the process of controlling the size and shape and preparing Au/Ag NPs using biological methods. Third, the applications in biology, tumor diagnosis and treatment, and other fields are reviewed to demonstrate the potential value of Au/Ag NPs. Finally, a discussion surrounding three aspects (similarity, individuality, and complementarity) of the two green synthesis processes is presented, and the necessary outlook, including the current limitations and challenges, is suggested, which provides a reference for the low-cost and sustainable production of Au/Ag NPs in the future.

Porcine viral diarrhea diseases affect the swine industry, resulting in significant economic losses. Porcine epidemic diarrhea virus (PEDV) genotypes G1 and G2, and groups A and C of the porcine rotavirus, are major etiological agents of severe gastroenteritis and profuse diarrhea, particularly among piglets, with mortality rates of up to 100%. Based on the high prevalence rate and frequent co-infection of PEDV, RVA, and RVC, close monitoring is necessary to avoid greater economic losses. We have developed a multiplex TaqMan probe-based real-time PCR for the rapid simultaneous detection and differentiation of PEDV subtypes G1 and G2, RVA, and RVC. This test is highly sensitive, as the detection limits were 20 and 100 copies/μL for the G1 and G2 subtypes of PEDV, respectively, and 50 copies/μL for RVA and RVC, respectively. Eighty-eight swine clinical samples were used to evaluate this new test. The results were 100% in concordance with the standard methods. Since reassortment between porcine and human rotaviruses has been reported, this multiplex test not only provides a basis for the management of swine diarrheal viruses, but also has the potential to impact public health as well.

Air quality is highly related to the health of a human being. Urban morphology has a significant influence on air quality; however, the specific relationship between urban morphology characteristics and air quality at the neighborhood scale has yet to be investigated, especially the vegetation effect on PM2.5 concentration and diffusion. The relevant morphological parameters based on the affected pathways of urban morphology on air quality were selected, and the sensitivity degree and laws of the selected morphological parameters to PM2.5 were quantified by numerical simulation, bivariate correlation analysis, and regression analysis. The results showed that Building Density (BD), Block Envelope Degree (BED), Average Building Volume (ABV), Average Building Floors (ABF), Standard Deviation of Building Height (SDH) and Greenbelt Coverage Rate (GCR) were Sensitive Morphological Parameters (SMPs). A positive and cosine curve trend of BD and BED with PM2.5 was observed. GCR was significant to dust retention along with vertical canopy height. When ABV = 40,000 m3 and ABF = 20F, the lowest PM2.5 concentration was examined, while increased SDH could promote airflow and enhance the capacity of PM2.5 diffusion. Finally, morphology-optimization strategies were proposed at the neighborhood scale: (1) Decreasing the BED along the street; (2) considering the species of vegetation with the appropriate height and increasing the GCR; (3) increasing the ABF of neighborhoods appropriately while controlling the ABV and distinguishing the internal SDH of neighborhoods. The study could apply the scientific basis for the planning and design of healthy and livable cities.

To conduct a comfortable lift for the care-receiver, it takes a lot of time and operations to design the motion trajectory for each care-receiver before transfer tasks. To solve this problem, this paper proposed a method to design a lift trajectory for a piggyback transfer robot. The robot, which can lift and move a person from a wheelchair to a bed or a pedestal pan, has been developed. The trajectory obtained by this method could make the robot conduct a comfort lift for the care-receiver, according to the weight and height of the care-receiver. A human-robot mechanics model and the relationship between the comfortable lift trajectory and the care-receiver’s weight and height were also contributed. According to the test results of 20 subjects, the force parameters used for trajectory design were determined, and the trajectory design method was optimized. The results of three subjects demonstrated that this method could conveniently and quickly provide a robot lift trajectory based on the subject’s weight and height, and this trajectory also achieved a similar lift as the trajectory designed by relying on the opinion of the subject. This method can be used for the design of the reference trajectory in the compliant control of the piggyback robot, which realizes the comfortable lifting of the care-receiver.

Transparent nano-ceramics have an important high-transmittance, material-integrating structure and function and a variety of potential applications, such as use in infrared windows, optical isolators, composite armors, intelligent terminal screens, and key materials of solid-state lasers. Transparent ceramics were originally developed to replace single crystals because of their low fabricating cost, controllable shape, and variable composition. Therefore, this study reviews and summarizes the development trends in transparent nano-ceramics and their potential applications. First, we review the research progress and application of laser nano-ceramic materials, focusing on the influence of controllable doping of rare earth ions on thermal conductivity and the realization of large-scale fabrication technology. Second, the latest research progress on magneto-optical transparent nano-ceramics, mainly including terbium gallium garnet (Tb3Ga5O12, TGG) ceramics and terbium aluminum garnet (Tb3Al5O12, TAG) ceramics, are summarized, and their performance is compared. Third, the research progress of transparent armor nano-ceramic materials, represented by MgAl2O3 and Aluminum oxynitride (AlON), are reviewed. Lastly, the progress in electro-optical transparent nano-ceramics and scintillation transparent nano-ceramics is reported, and the influence of the material-fabrication process on electro-optic effect or luminous intensity is compared. Moreover, the effect of particle diameter on fabrication, the relationship between nano powder and performance, and different sintering methods are discussed. In summary, this study provides a meaningful reference for low-cost and sustainable production in the future.

Abstract Background Retinal pigment epithelium (RPE) cells transfer oxygen and nutrients from choroid to the neural retina. Reduced oxygen to RPE perturbs development and functions of blood vessels in retina. Previous efforts of genome-wide studies have been largely focused on transcriptional changes of cells in response to hypoxia. Recently developed ribosome profiling provides an opportunity to study genome-wide translational changes. To gain systemic insights into the transcriptional and translational regulation of cellular in response to hypoxic stress, we used simultaneous RNA sequencing and ribosome profiling on an RPE cells line, ARPE-19, under hypoxia condition. Results Both HIF-1α and EPAS1 (HIF-2α) proteins were stabilized in ARPE-19 under hypoxic stress treatment at 1 h, 2 h and 4 h. Analysis of simultaneous RNA sequencing and ribosome profiling data showed genome-wide gene expression changes at both transcriptional and translational levels. Comparative analysis of ribosome profiling and RNA-seq data revealed that hypoxia induced changes of more genes at the translational than the transcriptional levels. Ribosomes densities at 5′ untranslated region (UTR) significantly increased under hypoxic stress. Interestingly, the increase in ribosome densities at 5′ UTR is positively correlated with the presence of upstream open reading frames (uORFs) in the 5′ UTR of mRNAs. Conclusion Our results characterized translational profiles of mRNAs for a RPE cell line in response to hypoxia. In particular, uORFs play important roles in the regulation of translation efficiency by affecting ribosomes loading onto mRNAs. This study provides the first attempt to understand translational response of mammalian cells under hypoxic condition.

Cancer is considered to have an adverse influence on health around the world. Chitosan, a linear polysaccharide that contains copolymers of β-1-4 linked d-glucosamine and N-acetyl-d-glucosamine units, has been widely used in the field of biomedicine, owing to its nontoxicity, biocompatibility, biodegradability, and hemocompatibility. This study was aimed at preparing the chitosan oligosaccharides (COS) and examining its ability on suppressing lung cancer in vitro and in vivo. Human non-small-cell lung cancer A549 cells model and C57BL/6 mice bearing lung cancer model were adopted. COS showed inhibition on the viability and proliferation of lung carcinoma cells (A549) in time-dependent manners, but no cytotoxicity to human liver cell (HL-7702). Moreover, COS could significantly increase Bax expression of A549 cells while decreasing Bcl-2 expression. COS supplementation significantly inhibited the growth of Lewis tissues and promoted necrosis of tumor cells in vivo. After treatment with COS, significantly elevated concentrations of Bax and reduced expression of Bcl-2 in tumor tissues, as well as elevated levels of TNF-α, IL-2, Fas and Fas-L in mice serum were observed (p < 0.05). In conclusion, COS had certain anti-tumor effects and potential application as a synergic functional food ingredient to prevent cancer.

Postmenopausal osteoporosis has seriously affected the life quality of elderly women. A natural polymer, chitin, obtained from shells of crab and shrimp, has been widely used in the biomedical field owing to its nontoxicity, biocompatibility, and biodegradability. In this study, natural N-acetyl-d-glucosamine (NAG) was prepared from liquefied chitin. The protective activities of NAG in postmenopausal osteoporosis were evaluated on Sprague Dawley rats and osteoblast-based models. Results showed that oral administration of NAG boosted trabecular bone volume and trabecular numbers. Additionally, the calcium content in the femur and tibia increased, and femoral biomechanical properties improved. Furthermore, NAG supplementation significantly lowered alkaline phosphatase levels and increased calcium content in the serum of ovariectomized rats. In vitro studies showed that NAG markedly promoted cell proliferation and stimulated osteoblast differentiation of mouse calvaria origin MC3T3-E1 cells with increased alkaline phosphatase activity in a concentration-dependent manner. Moreover, NAG effectively protected osteoblasts from oxidative damage induced by hydrogen peroxide. In conclusion, our data provide an additional foundation for dietary supplementation of NAG, which could protect and reverse osteopenia in postmenopausal women.