Search

Objective: CD4 + CD25 + Foxp3 + regulatory T (Treg) cell-mediated immunosuppression is an essential mechanism of rheumatoid arthritis (RA). However, little is known regarding the specific role of CD4 + CD25 - Foxp3 + Treg cells in RA. This study aimed to investigate the frequency of circulating CD4 + CD25 - Foxp3 + Treg cells and their role in RA., Methods: Sixty-one untreated RA patients and 40 healthy controls (HCs) were enrolled in this study. The proportion of CD4 + CD25 - Foxp3 + T cells and CD4 + CD25 + Foxp3 + Tregs; the levels of CTLA4, GITR, Helios, and ICOS; and the production of IL-17A, IFN-γ, and IL-10 were assessed by flow cytometry. The correlation of CD4 + CD25 - Foxp3 + T cells and CD4 + CD25 + Foxp3 + Tregs with the clinical indicators was conducted by Spearman correlation analysis., Results: The proportion of CD4 + CD25 - Foxp3 + T cells was elevated in RA and positively correlated with disease activity. CD4 + CD25 - Foxp3 + T cells expressed less Helios and produced more IFN-γ than conventional Tregs in RA. Additionally, the proportion of CD4 + CD25 - Foxp3 + T cells was positively correlated with DAS28 score, IgG titer, and anti-CCP titer., Conclusions: These data indicate that CD4 + CD25 - Foxp3 + T cells in RA exhibit several different functional properties from conventional Tregs and are correlated with RA disease activity., (© 2022. The Author(s).)

Two new organic acids, identified as (7 E ,9 E ,12 E )-pentadecyl-7,9,12-trienoic acid, named Oleraceacid A ( 1 ), and 6,7-dihydroxy-4-(4-hydroxy-3,5-dimethoxyphenyl)-2-naphthoic acid, named Oleraceacid B ( 2 ), were isolated from Portulaca oleracea L.. The structures were verified by spectroscopic methods, including UHPLC-ESI-QTOF/MS, 1 D and 2 D NMR. Both Oleraceacid A ( 1 ) and Oleraceacid B ( 2 ) at 20 μM inhibited the inflammatory factor, IL-1 β in the RAW 264.7 cells induced by LPS, moreover, Oleraceacid A ( 1 ) can inhibit cholinesterase activity.

Next generation textile-based wearable sensing systems will require flexibility and strength to maintain capabilities over a wide range of deformations. However, current material sets used for textile-based skin contacting electrodes lack these key properties, which hinder applications such as electrophysiological sensing. In this work, a facile spray coating approach to integrate liquid metal nanoparticle systems into textile form factors for conformal, flexible, and robust electrodes is presented. The liquid metal system employs functionalized liquid metal nanoparticles that provide a simple "peel-off to activate" means of imparting conductivity. The spray coating approach combined with the functionalized liquid metal system enables the creation of long-term reusable textile-integrated liquid metal electrodes (TILEs). Although the TILEs are dry electrodes by nature, they show equal skin-electrode impedances and sensing capabilities with improved wearability compared to commercial wet electrodes. Biocompatibility of TILEs in an in vivo skin environment is demonstrated, while providing improved sensing performance compared to previously reported textile-based dry electrodes. The "spray on dry-behave like wet" characteristics of TILEs opens opportunities for textile-based wearable health monitoring, haptics, and augmented/virtual reality applications that require the use of flexible and conformable dry electrodes., (© 2022 Wiley-VCH GmbH.)

The dispersion of silica dioxide (SiO 2 )/sodium lauryl sulfate (SDS) has been widely used in hydrocarbon reservoirs, but its instability is still a problem in practical engineering applications. The dispersion morphology of SiO 2 nanoparticles before and after modification was studied by TEM, and the thermal stability of different foam dispersions was evaluated by FoamScan. In this paper, the mechanism of foam stability was investigated by combining the measurement of interfacial energy of nanoparticles at the gas-liquid interface with dynamics simulation of molecular diffusion. The results showed that SiO 2 /SDS dispersions had good thermal stability due to the synergistic effect of SiO 2 nanoparticles and SDS. The addition of SiO 2 nanoparticles improved the interfacial energy and interfacial activity at the gas-liquid interface, meanwhile limited the movement of SDS molecules and water molecules, which was beneficial for foam stability. Notably, the addition of modified SiO 2 nanoparticles further enhanced the interfacial energy at the gas-liquid interface and strengthened the restriction of water/SDS molecular movement, thereby slowing down the drainage and decay of the foam dispersions. The mechanism investigation of SiO 2 /SDS dispersions was of benefit to foam flooding in hydrocarbon reservoirs., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The SARS-CoV-2 vaccines have been widely used to build an immunologic barrier in the population against the COVID-19 pandemic. However, a newly emerging Omicron variant, including BA.1, BA.1.1, BA.2, and BA.3 sublineages, largely escaped the neutralization of existing neutralizing antibodies (nAbs), even those elicited by three doses of vaccines. Here, we used the Omicron BA.1 RBD as a fourth dose of vaccine to induce potent Omicron-specific nAbs and evaluated the broadly neutralizing activities against SARS-CoV-2 variants. The BA.1-based vaccine was indeed prone to induce a strain-specific antibody response substantially cross-reactive with BA.2 sublineage, and yet triggered broad neutralization against SARS-CoV-2 variants when it was used in the sequential immunization with WT and other variant vaccines. These results demonstrated that the booster of Omicron RBD vaccine could be a rational strategy to enhance the broadly nAb response., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Ionizable cationic lipids have great potential for gene delivery, yet the effect of the molecular structure of such lipids on gene delivery efficiency is an ongoing research challenge. To better understand corresponding structure-function activity relationships, we synthesized four ester-linked, pH-responsive, ionizable cationic lipids. The screened DEDM4 lipid, containing 2-ethylenedimethylamine in the headgroup and a branched-chain tail, exhibited a high delivery efficacy of plasmid DNA and siRNA in A549 cells, which was comparable with that of the commercial reagent lipofectamine 3000 (lipo3000). Moreover, because of its pK a value of 6.35 and pH-sensitivity under acidic conditions, DEDM4 could carry sufficient positive charge in the acidic environment of endosomes and interact with the endosome lumen, leading to destruction of the endomembrane and subsequent release of siRNA into the cytoplasm with endosomal escape. Furthermore, we used DEDM4 to deliver IGF-1R siRNA to induce cancer cell apoptosis, thereby leading to great tumor inhibition. More importantly, it also showed very low toxicity in vivo. These structure-activity data for DEDM4 demonstrate potential clinical applications of DEDM4-mediated gene delivery for cancer., (Copyright © 2022. Published by Elsevier B.V.)

This literature review focuses on land quality evaluation (LQE) and its effects on sustainable development through quantitative analysis and value-added information. In contrast to the traditional perspective, a structured review based on bibliometric indicators and social network analysis allows identifying hidden evidence for answering the following research questions: (i) What: What is the application of LQE? (ii) Which: Which sustainable development goals does the application contribute to? (iii) Why and how: What are the main applications and methods of each topic? (iv) Where: Where is the hotspot of the problem? What is the future research orientation of the topic? (v) How and when: How has the topic grown since 2000? Data investigation explores 4029 articles in 2000-2019 from four publishers. With the support of VOSviewer software, six clusters corresponding to six main applications of LQE are classified. Overlapping keywords in several clusters are resolved by the binary term frequency counter for the cluster preference determination. After conducting the data verification and editing process, a structured review is performed again with systematic research questions. This research offers a synthesis of traditional and novel quantitative analysis for literature review, which is comprehensive, accurate, and reliable., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Because of the complexity of cancer ecosystems, the efficacy of single-agent chemotherapy is limited. Herein, we report the use of cationic nanoparticles (designated PPCNs) generated from a chemically modified form of the chemotherapeutic agent podophyllotoxin (PPT) to deliver both microRNA-424 (miR-424) and PPT to tumor cells, thus combining chemotherapy and gene therapy. We evaluated the optimal loading ratio of miR-424─which targets programmed cell death ligand 1 (PD-L1) mRNA and reduces PD-L1 production, thus promoting the attack of tumor cells by T cells─for effective delivery of miR-424 and PPCNs into nonsmall-cell lung cancer cells (H460). Because miR-424 can reverse chemotherapy resistance, treatment of the tumor cells with the combination of miR-424 and PPT enhanced their sensitivity to PPT. Because miR-424 and the PPCNs regulated PD-L1 production in different ways, the miR-424@PPCN complexes were significantly more efficacious than either miR-424 or PPCNs alone. We also demonstrated that treatment of tumor-bearing mice with these complexes significantly inhibited tumor growth and extended survival. Moreover, additional in vitro experiments revealed that the complexes could remodel the tumor immune microenvironment, relieve immunosuppression, and achieve immune normalization. This novel system for delivering a combination of PPT and miR-424 shows great potential for the multimodal treatment of lung cancer.

Aeschynomene indica has a distinctive symbiosis with Bradyrhizobium in which nodulation is Nod factor-independent. In this study, we characterised three Gram-negative and rod-shaped strains (83002 T , 81013 and 83012) isolated from root nodules of Aeschynomene indica in Shandong Peninsula. The major cellular fatty acids of isolates were C 16:0 , C 18:0 , C 18:1 ω7c 11-methyl, summed feature 3 and summed feature 8. The major polar lipids were phosphatidylethanolamine (PE), aminolipids (AL) and phosphatidylcholine (PC). Phylogenetic analysis based on the 16S rRNA locus showed that they belonged to the Bradyrhizobium genus, and shared the highest similarity to the type strains Bradyrhizobium oligotrophicum S58 T and Bradyrhizobium denitrificans LMG 8443 T . As expected, analysis of concatenated sequences of six housekeeping genes (atpD, recA, glnII, dnaK, gyrB, and rpoB) and nifH gene proposed that these three strains formed a distinct clade within the genus Bradyrhizobium. The highest average nucleotide identity and DNA-DNA hybridization values of the three strains in comparison to the closest Bradyrhizobium species were 87.5% and 65.3%, respectively, which are far below the threshold of species delineation, and thus confirmed the three strains as a new species. The genome size of strain 83002 T is 7.52 Mbp, and the DNA G+C content is 65.42 mol%. Strain 83002 T (=KCTC 82266 T =MCCC 1K04775 T ) was chosen as the type strain of the new species, for which the name Bradyrhizobium aeschynomenes sp. nov. was proposed., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: The rates of hepatitis B virus (HBV) infection in rheumatoid arthritis (RA) patients are controversial when considering the reported outcomes. It was speculated that HBV infection status was altered after RA, and variations inn HBV infection rates became apparent., Methods: To compare the positive proportions of hepatitis B e antigen (HBeAg) and HBV DNA, a retrospective case-control study was performed between 27 chronic hepatitis B (CHB) patients with RA and 108 age- and gender-matched CHB patients. In addition, the positivity rates of hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) were surveyed among the 892 RA patients., Results: Compared to CHB patients, CHB patients with RA exhibited lower rates of HBeAg positivity (11.1% vs. 35.2%, P = 0.003), HBV DNA positivity (37.0% vs. 63.9%, P = 0.007) and ALT elevation (11.1% vs. 35.2%, P = 0.024). In the 892 RA patients, the prevalence of HBsAg (3.0%) was lower than that reported in the Chinese national data (7.2%), whereas the anti-HBc positivity rate of 44.6% was higher than that of 34.1%., Conclusion: HBV infection status was altered after suffering from RA. Compared to the matched CHB patients, low positive proportions of HBeAg and HBV DNA were observed for CHB patients with RA., (© 2022. The Author(s).)

The different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have attracted most public concern because they caused "wave and wave" COVID-19 pandemic. The initial step of viral infection is mediated by the SARS-CoV-2 Spike (S) protein, which mediates the receptor recognition and membrane fusion between virus and host cells. Neutralizing antibodies (nAbs) targeting the S protein of SARS-CoV-2 have become promising candidates for clinical intervention strategy, while multiple studies have shown that different variants have enhanced infectivity and antibody resistance. Here, we explore the structure and function of STS165, a broadly inter-Spike bivalent nAb against SARS-CoV-2 variants and even SARS-CoV, contributing to further understanding of the working mechanism of nAbs., Competing Interests: Patent application has been filed on the monoclonal antibody STS165 (patent application number: 202210489241.1; patent applicants: National Clinical Research Center for Infectious Disease and Shenzhen Third People’s Hospital). Q.F., B.Z., F.Q., B.J., and Z.Z. are inventors., (© 2022.)

Striking number of mutations found in the spike protein of recently emerged SARS-CoV-2 Omicron subvariants BA.1, BA.2, BA.3 and BA.4/5 has raised serious concerns regarding the escape from current antibody therapies and vaccine protection. Here, we conducted comprehensive analysis on the extent of two major Omicron lineages BA.1/BA.1.1 and BA.2 to escape neutralization from the therapeutic antibodies approved by the regulatory authorities and convalescent plasma from SARS-CoV-2 patients infected during initial wave of pandemic in early 2020. We showed that Omicron BA.1/BA.1.1 were the most resistant in both magnitude and breadth against antibodies and convalescent plasma, followed by Beta, BA.2, Gamma, Delta and Alpha. While the majority of therapeutic antibodies lost binding and neutralization to Omicron variants, BRII combo (BRII-196 + BRII-198), S309, and AZ combo (COV2-2196 + COV2-2130) maintained neutralization despite of reduction due to either conserved epitope or combinational effect between the two designated antibodies. A single intraperitoneal injection of BRII combo as a prophylactic treatment protected animals from Omicron infection. Treated animals manifested normal body weight, survived infection up to 14 days, undetectable levels of infectious viruses in the lungs, and reduced lung pathology compared to the controls. Analyzing ACE2 from diverse host species showed that Omicron variants acquired ability to use mouse ACE2 for entry. These results demonstrate major antigenic shifts and potentially broadening the host range of two major Omicron lineages BA.1/BA.1.1 and BA.2, posing serious challenges to current antibody therapies and vaccine protection as well as increasing danger of spillover into the wildlife., Competing Interests: The authors have filed patent applications on antibodies BRII-196 and BRII-198 described in the manuscript. LZ, QZ, and XS are shareholders of TSB Therapeutics., (Copyright © 2022 Wang, Zhang, Zhang, Aw, Chen, Wong, Hong, Ju, Shi, Ding, Zhang, Chu and Zhang.)

To determine original gas-in-place, this study establishes a flowing material balance equation based on the improved material balance equation for shale gas reservoirs. The method considers the free gas in the matrix and fracture, the dissolved gas in kerogen, and the pore volume occupied by adsorbed phase simultaneously, overcoming the problem of incomplete consideration in the earlier models. It also integrates the material balance method with the flowing material balance method to obtain the average formation pressure, eliminating the problem with the previous method where shutting down of wells was needed to monitor the formation pressure. The volume of the adsorbed gas on the ground is converted into volume of the adsorbed phase in the formation using the volume conservation method to characterize the pore volume occupied by the adsorbed phase, which solves the problem of the previous model that the adsorbed phase was neglected in the pore volume. The model proposed in this study is applied to the Fuling Shale Gas Field in southwest China and compared with other flowing material balance equations, and the results show that the single-well control area calculated by the model proposed in this study is closer to the real value, indicating that the calculations in this study are more accurate. Furthermore, the calculations show that the dissolved gas takes up a large fraction of the total reserves and cannot be ignored. The sensitivity analyses of critical parameters demonstrate that (a) the greater the porosity of the fracture, the greater the free gas storage; (b) the values of Langmuir volume and TOC can significantly affect the results of the reservoir calculation; and (c) the adsorbed phase occupies a smaller pore volume when the Langmuir volume is smaller, the Langmuir pressure is higher, or the adsorbed phase density is higher. The findings of this study can provide better understanding of the necessity to take into account the dissolved gas in the kerogen, the pore volume occupied by the adsorbed phase, and the fracture porosity when evaluating reserves. The method could be applied to the calculation of pressure, recovery of free gas phase and adsorbed phase, original gas-in-place, and production predictions, which could help for better guidance of reserve potential estimations and development strategies of shale gas reservoirs., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

A recently identified SARS-CoV-2 variant, Lambda, has spread to many countries around the world. Here, we measured and evaluated the reduced sensitivity of Lambda variant to the neutralization by plasma polyclonal antibodies elicited by the natural SARS-CoV-2 infection and inactivated vaccine. The combination of two substitutions appearing in the RBD of spike protein (L452Q and F490S) resulted in noticeably reduced neutralization against Lambda variant. F490S contributed more than L452Q in affecting the neutralization. In addition, the neutralization test with 12 published nAbs binding to RBD of SARS-CoV-2 with defined structures suggested that Lambda variant resisted the neutralization by some antibodies from Class 2 and Class 3. Overall, these results suggest that pre-existing antibody neutralization established by natural infection from non-Lambda variants or immunization could be significantly decreased, re-emphasizing the importance of ongoing viral mutation monitoring., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

The majority of diffuse midline gliomas, H3 K27-altered (DMG-H3 K27-a), are infiltrating pediatric brain tumors that arise in the pons with no effective treatment. To understand how clonal evolution contributes to the tumor's invasive spread, we performed exome sequencing and SNP array profiling on 49 multi-region autopsy samples from 11 patients with pontine DMG-H3 K27-a enrolled in a phase I clinical trial of PDGFR inhibitor crenolanib. For each patient, a phylogenetic tree was constructed by testing multiple possible clonal evolution models to select the one consistent with somatic mutations and copy number variations across all tumor regions. The tree was then used to deconvolute subclonal composition and prevalence at each tumor region to study convergent evolution and invasion patterns. Somatic variants in the PI3K pathway, a late event, are enriched in our cohort, affecting 70% of patients. Convergent evolution of PI3K at distinct phylogenetic branches was detected in 40% of the patients. 24 (~ 50%) of tumor regions were occupied by subclones of mixed lineages with varying molecular ages, indicating multiple waves of invasion across the pons and extrapontine. Subclones harboring a PDGFRA amplicon, including one that amplified a PDGRFA Y849C mutant allele, were detected in four patients; their presence in extrapontine tumor and normal brain samples imply their involvement in extrapontine invasion. Our study expands the current knowledge on tumor invasion patterns in DMG-H3 K27-a, which may inform the design of future clinical trials., (© 2022. The Author(s).)

The SARS-CoV-2 nucleocapsid protein (NP) is an important indicator for the virus infection, highlighting the crucial role of NP-specific monoclonal antibodies (mAbs) used in multiple biochemical assays and clinical diagnosis for detecting the NP antigen. Here, we reported a pair of noncompeting human NP-specific mAbs, named P301-F7 and P301-H5, targeting two distinct linear epitopes on SARS-CoV-2 or SARS-CoV. We evaluated the application of P301-F7 in the analysis of enzyme linked immunosorbent assay, western blot, flow cytometry, immunofluorescence, and focus reduction neutralization test. We for the first time report a broad mAb effectively recognizing various live viruses of SARS-CoV-2 variants including Alpha, Beta, Delta, and Omicron, indicating a wide range of application prospects., (© 2022. The Author(s).)

The mammary gland epithelial tree contains two distinct cell populations, luminal and basal. The investigation of how this heterogeneity is developed and how it influences tumorigenesis has been hampered by the need to perform studies on these populations using animal models. Comma-1D is an immortalized mouse mammary epithelial cell line that has unique morphogenetic properties. By performing single-cell RNA-seq studies, we found that Comma-1D cultures consist of two main populations with luminal and basal features, and a smaller population with mixed lineage and bipotent characteristics. We demonstrated that multiple transcription factors associated with the differentiation of the mammary epithelium in vivo also modulate this process in Comma-1D cultures. Additionally, we found that only cells with luminal features were able to acquire transformed characteristics after an oncogenic HER2 (also known as ERBB2) mutant was introduced in their genomes. Overall, our studies characterize, at a single-cell level, the heterogeneity of the Comma-1D cell line and illustrate how Comma-1D cells can be used as an experimental model to study both the differentiation and the transformation processes in vitro., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

With an in-depth understanding of noncoding ribonucleic acid (RNA), many studies have shown that microRNA (miRNA) plays an important role in human diseases. Because traditional biological experiments are time-consuming and laborious, new calculation methods have recently been developed to predict associations between miRNA and diseases. In this review, we collected various miRNA-disease association prediction models proposed in recent years and used two common data sets to evaluate the performance of the prediction models. First, we systematically summarized the commonly used databases and similarity data for predicting miRNA-disease associations, and then divided the various calculation models into four categories for summary and detailed introduction. In this study, two independent datasets (D5430 and D6088) were compiled to systematically evaluate 11 publicly available prediction tools for miRNA-disease associations. The experimental results indicate that the methods based on information dissemination and the method based on scoring function require shorter running time. The method based on matrix transformation often requires a longer running time, but the overall prediction result is better than the previous two methods. We hope that the summary of work related to miRNA and disease will provide comprehensive knowledge for predicting the relationship between miRNA and disease and contribute to advanced computation tools in the future., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We report a new synthetic strategy of combining N -carboxyanhydride (NCA) chemistry and photonic crystals for the fabrication of polypeptide structural color films. Driven by surface-initiated ring-opening polymerization, the di-NCA derivative of l-cystine (Cys) is introduced to replicate the functionalized colloidal crystal templates and construct freestanding P(Cys) films with tunable structural color. Furthermore, the feasibility of preparing patterned polypeptide photonic films is demonstrated via template microfabrication. Because of the incorporation of l-glutamate (Glu) components, the P(Cys- co -Glu) co-polypeptide films are endowed with a visual color responsiveness toward pH changes. Additionally, the polypeptide photonic films show on-demand degradability. Given the large family of amino acid building blocks, this powerful and versatile approach paves the way for chemical derivatization of multifunctional peptide-based optical platforms.

A novel lignan, identified as 4-(3,4-dihydroxyphenyl)-6,7-dimethoxy-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one, named oleralignan A ( 1 ), together with six known compounds, loliolide ( 2 ), isololiolide ( 3 ), dehydrololiolide ( 4 ), daphnetin ( 5 ), esculetin ( 6 ), and trans-coumaric acid methyl ester ( 7 ) was obtained from Portulaca oleracea L., while compounds 3 , 4 , 6 , and 7 were isolated from the plant for the first time. Their structures were elucidated using spectroscopic methods, including one- and two-dimensional NMR and high-resolution electrospray ionization time-of-flight mass spectrometry. In addition, the results of activity assay demonstrated that compounds 1 - 7 have anticholinesterase activities.

Ionizable lipids are the leading vectors for gene therapy. Understanding the effects of molecular structure on efficient gene delivery is one of the most important challenges for maximizing the utility of such lipid vectors. We synthesized an array of pH-responsive and ionizable lipids to investigate the relationship between lipid structure and activity. The optimized lipid (EDM) has double tertiary amines in the headgroup and an ester linker. EDM exhibited efficient DNA and siRNA delivery to, and gene silencing of, A549 cells. EDM has a pK a value of 6.67, which enabled it to quickly escape from the endosome after entering the cell; the ester linkages rapidly degraded and enabled gene release into the cytoplasm. EDM also delivered IGF-1R siRNA to inhibit tumor growth and induce cancer cell apoptosis by efficient inhibition of IGF-1R expression in mice. Our study on the structure-activity relationships of ionizable lipids will facilitate clinical applications., (Copyright © 2022. Published by Elsevier B.V.)

Metabolic reprogramming of immune cells has been proven to be important for systemic lupus erythematosus (SLE). This study aims to understand the role of SLC7A5, an amino acid transporter, in SLE. We analyzed SLC7A5 mRNA expression of SLE patients compared to healthy controls using GEO database, and found that it was increased in CD4 + T cells and CD19 + B cells. We then confirmed the expression up-regulation using flow cytometry and found that the proportion of SLC7A5 + cells and its expression were increased in peripheral blood T and B cells from SLE patients. Importantly, SLC7A5 expression in T and B cells was positively correlated with blood urea nitrogen and serum creatinine. Therefore, we conclude that SLC7A5, up-regulating in circulating T and B cells, correlates with kidney function, suggesting its potential role in mediating renal damage in SLE, which provides novel insight into SLE pathogenesis and provides a potential biomarker for disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Past swarm intelligence algorithms for solving UAV path planning problems have suffered from slow convergence, lack of complex constraints and guidance for local optimisation. It no longer meets the requirements of the Multi-UAV Cooperative Reconnaissance Mission Planning (MUCRMP) problem in the context of multi-radar detection. In this paper, a global optimisation model with the objective of a shorter distance within radar detection range of the UAV is proposed at first, including the planning of reconnaissance sequence between and within target groups, relative position to targets. More importantly, the imaging characteristics of the UAV and its minimum turning radius have been considered in depth in this study. Then an improved synthetic heuristic algorithm is proposed to solve the model, which obtains valuable reconnaissance mission plan. Finally, an example solution for a problem with 68 target point sizes is carried out, and the validity and feasibility of the model and algorithm are illustrated through the analysis given. Compared with the existing algorithms, the improved synthetic heuristic algorithm can give better anti-radar attributes to the UAV and efficiently improved the convergence speed in the specific reconnaissance mission.

Low drug delivery efficiency elevates the cost of medication, lowers the therapeutic efficacy, and appears as a leading reason for unmet needs in anticancer therapies. Herein, we report the development of self-assembled podophyllotoxin-loaded lipid bilayer nanoparticles that inhibit the production of programmed cell death ligand 1 in lung cancer cells and promote tumor-specific immune responses, thus offering a strategy for regulating the immunosuppressive microenvironment of tumors. In addition, encapsulation of podophyllotoxin in the nanoparticles reduced its systemic toxicity, enhanced its penetration into tumors, and increased its antitumor efficacy. Systemic injection of the nanoparticles into tumor-bearing mice not only prevented tumor immune escape but also significantly inhibited tumor growth and extended survival. In general, the podophyllotoxin-loaded nanoparticles exhibited both immunological effects and antitumor effects in addition to having better targeting activity and fewer side effects than free podophyllotoxin. We expect our findings to facilitate the development of therapies for lung cancer.

Introduction: Biomarkers of bone and cartilage metabolism were proposed as early diagnosis indicators for knee osteoarthritis (OA), however, which were influenced by disease stage, age, and menopause state. Accurate diagnosis indicators are eagerly awaited. The current study aims to investigate associations of joint metabolism biomarkers and bone mineral density (BMD) with early knee OA in males and premenopausal females before age 50 years., Method: A total of 189 patients aged before 50 years with early knee OA and 152 healthy participants were enrolled. Levels of bone biomarkers (PINP, OC, and CTX-I) and cartilage biomarkers (PIIANP, COMP, CTX-II, and MMP-3) were assessed. BMD was measured at the lumbar, femoral neck, and hip. Multivariate regression analyses were performed to evaluate the relationship between biomarkers, BMD, and early knee OA., Results: Serum COMP, urine CTX-II and BMD at femoral neck and hip were increased in premenopausal patients as compared to control; with serum PINP and OC reduced. Meanwhile, serum COMP, urine CTX-II, and BMD at femoral neck and hip showed positive associations with premenopausal early knee OA, while serum PINP had negative association. However, in male patients, only serum COMP was higher than control, and no association of biomarkers or BMD was found with early knee OA., Conclusions: The joint metabolism biomarkers and BMD showed multiple associations with early knee OA in premenopausal females, but not in males aged before 50 years. It was suggested that sex differences should be taken into account when evaluating cartilage and bone metabolism in early knee OA. Key Points • The joint metabolism biomarkers and BMD are associated with early knee OA in premenopausal females, but not in males aged before 50 years. • Sex differences should be taken into account when evaluating cartilage and bone metabolism in early knee OA., (© 2021. International League of Associations for Rheumatology (ILAR).)

Background: Identification of potential novel targets for reversing resistance to Epidermal Growth Factor Receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) holds great promise for the treatment of relapsed lung adenocarcinoma (LUAD). In the present study, we aim to investigate the role of methyltransferase-like 7B (METTL7B) in inducing EGFR-TKIs resistance in LUAD and whether it could be a therapeutic target for reversing the resistance., Methods: METTL7B-overexpressed LUAD cell lines, gefitinib and osimertinib-resistant Cell-Derived tumor Xenograft (CDX) and Patient-Derived tumor Xenograft (PDX) mouse models were employed to evaluate the role of METTL7B in TKIs resistance. Ultraperformance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) was used to identify the metabolites regulated by METTL7B. Methylated RNA immunoprecipitation (MeRIP)-qPCR analysis was performed to measure the N 6 -methyladenosine (m 6 A) status of mRNA of METTL7B targeted genes. Gold nanocluster-assisted delivery of siRNA targeting METTL7B (GNC-siMETTL7B) was applied to evaluate the effect of METTL7B in TKIs resistance., Results: Increased expression of METTL7B was found in TKIs-resistant LUAD cells and overexpression of METTL7B in LUAD cells induced TKIs resistance both in vitro and in vivo. Activated ROS-metabolism was identified in METTL7B-overexpressed LUAD cells, accompanied with upregulated protein level of GPX4, HMOX1 and SOD1 and their enzymatic activities. Globally elevated m 6 A levels were found in METTL7B-overexpressed LUAD cells, which was reduced by knock-down of METTL7B. METTL7B induced m 6 A modification of GPX4, HMOX1 and SOD1 mRNA. Knock-down of METTL7B by siRNA re-sensitized LUAD cells to gefitinib and osimertinib both in vitro and in vivo., Conclusions: This study uncovered a new critical link in METTL7B, glutathione metabolism and drug resistance. Our findings demonstrated that METTL7B inhibitors could be used for reversing TKIs resistance in LUAD patients., (© 2022. The Author(s).)

Rolling enables the directional alignment of the reinforcements in graphene/Cu composites while achieving uniform graphene dispersion and matrix grain refinement. This is expected to achieve a breakthrough in composite performance. In this paper, the process parameters of rolling are investigated, and the defects, thickness variations of graphene and property changes of the composite under different parameters are analyzed. High-temperature rolling is beneficial to avoid the damage of graphene during rolling, and the prepared composites have higher electrical conductivity. The properties of graphene were investigated. Low-temperature rolling is more favorable to the thinning and dispersion of graphene; meanwhile, the relative density of the composites is higher in the low-temperature rolling process. With the increase of rolling deformation, the graphene defects slightly increased and the number of layers decreased. In this paper, the defect states of graphene and the electrical conductivity with different rolling parameters is comprehensively investigated to provide a reference for the rolling process of graphene/copper composites with different demands.

Objectives: Abnormalities and hyperactivation of B cells have been described in idiopathic inflammatory myopathies (IIM). However, little is known about changes in the homeostasis of peripheral blood B cells in adult IIM patients. The aim of this study was to identify phenotypic alterations of B cell subsets and their relation to the overall clinical profile., Methods: Blood samples were collected from 25 adult IIM patients and 15 healthy controls. Peripheral B cell subsets were classified into non-switched memory B cells (CD19+CD27+lgD+), switched memory B cells (CD19+CD27+lgD-), double-negative (DN) memory B cells (CD19+CD27-lgD-) and naïve B cells (CD19+CD27-lgD+) based on their surface phenotype as measured by flow cytometry. The clinical profile of IIM and its correlation with B cell subsets was further evaluated., Results: Frequencies of CD19+ B cells and naïve B cells were increased in adult IIM patients compared with healthy controls (p=0.005 and p<0.001, respectively) and the frequency of memory B cells was decreased (p<0.001). Moreover, patients with a rash had lower non-switched memory B cells proportion (p=0.032). Patients with anti-MDA5+ antibodies had higher CD19+ B cells proportion than anti-ARS+ patients (p=0.046). Patients who were not receiving treatment had elevated levels of CD19+ B cells and naïve B cells along with reduced non-switched memory B cells compared with patients who were receiving treatment (p=0.021, p=0.036 and p=0.032, respectively)., Conclusions: Our findings demonstrate abnormalities in the homeostasis of the B cell subsets present in adult IIM patients, characterised by expanded CD19+ B cells and naïve B cells but reduced memory B cells. Phenotypic abnormalities of B cell subsets are associated with the presence of a rash, with anti-MDA5 positivity and with treatment.

Frankincense-Myrrh is a classic drug pair that promotes blood circulation, and eliminates blood stasis. The combination of the two drugs has a definite clinical effect on the treatment of cerebrovascular diseases (CBVDs), but its mechanism of action and compatibility have not been elucidated. In this study, the bioactive components, core targets, and possible synergistic mechanisms of Frankincense-Myrrh in the treatment of CBVDs are explored through systems pharmacology combined with in vivo and in vitro experiments. Comparing target genes of components in Frankincense and Myrrh with CBVD-related genes, common genes were identified; 15 core target genes of Frankincense-Myrrh for the treatment of CBVDs were then identified using protein-protein interaction (PPI) analysis. It was also predicted through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis that the molecular mechanism of Frankincense-Myrrh action on CBVDs was mainly related to the regulation of neurotrophic factors and inflammatory responses. Frankincense-Myrrh significantly improved neurological function, decreased infarct volume, alleviated histopathological damage, inhibited microglial expression, and promoted the expression of neurons in middle cerebral artery occlusion (MCAO)-induced rats. The results of this study not only provide important theoretical support and experimental basis for the synergistic effect of Frankincense-Myrrh, but also provide new ideas for the prevention and treatment of cerebral ischemic injuries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liao, Wang, Guo, Bai, Ju, Ran, Hu, Yang, Wen and Ding.)

The current COVID-19 pandemic caused by constantly emerging SARS-CoV-2 variants still poses a threat to public health worldwide. Effective next-generation vaccines and optimized booster vaccination strategies are urgently needed. Here, we sequentially immunized mice with a SARS-CoV-2 wild-type inactivated vaccine and a heterologous mutant RBD vaccine, and then evaluated their neutralizing antibody responses against variants including Beta, Delta, Alpha, Iota, Kappa, and A.23.1. These data showed that a third booster dose of heterologous RBD vaccine especially after two doses of inactivated vaccines significantly enhanced the GMTs of nAbs against all SARS-CoV-2 variants we tested. In addition, the WT and variants all displayed good cross-immunogenicity and might be applied in the design of booster vaccines to induce broadly neutralizing antibodies., (© 2022. The Author(s).)

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by B cell dysregulation and the breakdown of self-tolerance, leading to pathogenic autoantibody production. Human Siglec-10 is a member of the sialic acid-binding immunoglobulin-type lectin (Siglec) family and a B cell surface coreceptor that inhibits B cell receptor-induced signalling. However, to date, no report has investigated CD19 + Siglec-10 + B cells in SLE patients. Thus, this study aimed to measure the population of CD19 + Siglec-10 + B cells in patients with SLE and its correlation with disease activity., Methods: Flow cytometry was employed to measure the population of CD19 + Siglec-10 + B cells in peripheral blood mononuclear cells (PBMCs) of both SLE patients and healthy controls (HCs). The correlation of the proportion of CD19 + Siglec-10 + B cells with the values of SLE disease activity was analysed. PBMCs from HCs were challenged with serum from active SLE, inactive SLE, or HCs, and the proportion of CD19 + Siglec-10 + B cells was then assessed. The effect of dexamethasone (DEX) or hydroxychloroquine (HCQ) treatment on the proportion of CD19 + Siglec-10 + B cells in PBMCs from SLE patients was also determined., Results: The proportion of CD19 + Siglec-10 + B cells in SLE patients was significantly elevated (P < 0.05), correlated positively with the SLEDAI score (r = 0.304; P = 0.018) and negatively with complement component 3 (C3) (r = -0.283; P = 0.04). In vitro assays indicated that sera from active SLE patients could significantly enhance the proportion of CD19 + Siglec-10 + B cells (P < 0.05), while HCQ treatment significantly attenuated their proportions (P < 0.01)., Conclusions: The elevation of CD19 + Siglec-10 + B cells and their correlation with disease activity may suggest a role for Siglec-10 in the pathogenesis and progression of SLE and provide a serum biomarker for SLE activity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The QT interval prolongation was associated with fatal arrhythmias and cardiac death. However, there were not adequate data to clarify the situation of QT interval prolongation in primary biliary cholangitis (PBC) patients. The aim of this study was to clarify the rate and the associated risk factors of corrected QT (QTc) interval prolongation in PBC patients., Methods: From January 2016 to December 2020, PBC patients were retrospectively enrolled. The rate of QTc interval prolongation was surveyed and the associated risk factors were clarified by univariate and multivariate analyses., Results: Among the 189 PBC patients, 24.3% (46/189) had the QTc interval prolongation. The univariate analysis showed that age, Child-Pugh classification, creatinine, international normalized ratio (INR), and platelet (PLT) were associated with QTc interval prolongation in the PBC patients. The multivariate analysis further showed only age (p = .028) and Child-Pugh classification (p = .035) were the associated risk factors. It had the highest risk of QTc interval prolongation (as high as 64.3%) in the patients who were more than 62.5 years old and with Child-Pugh C., Conclusion: The QTc interval prolongation was frequent in PBC patients, especially in the patients with decompensated cirrhosis. The rate of QTc interval prolongation was as high as 64.3% in the PBC patients who were more than 62.5 years old and classified as Child-Pugh C., (© 2021 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Graphene has extremely high theoretical strength and electrothermal properties, and its application to Cu-based composites is expected to achieve a breakthrough in the performance of existing composites. As a nano-reinforced body, graphene often needs a long time of ball milling to make it uniformly dispersed, but the ball milling process inevitably brings damage to the graphene, causing the performance of the composite to deviate from expectations. Therefore, this paper uses CH 4 as a carbon source to repair graphene through a CVD process to prepare low-damage graphene/Cu composites. The process of graphene defect generation was studied through the ball milling process. The effects of defect content and temperature on the graphene repair process were studied separately. The study found that the graphene defect repair process, the decomposition process of oxygen-containing functional groups, and the deposition process of active C atoms existed simultaneously in the CVD process. When the repair temperature was low, the C atom deposition process and the oxygen-containing functional group decomposition process dominated. In addition, when the repair temperature is high, the graphene defect repair process dominated. 3 wt% graphene/Cu composites were prepared by pressure infiltration, and it was found that the bending strength was increased by 48%, the plasticity was also slightly increased, and the thermal conductivity was increased by 10-40%. This research will help reduce graphene defects, improve the intrinsic properties of graphene, and provide theoretical guidance for the regulation of C defects in composites.

Background: Malrotation after nailing of femoral shaft fractures occurs in about 25% of cases. It can cause substantial functional problems. The lesser trochanter (LT) profile has been used to assess rotational alignment. However, the extent to which the LT profile is symmetrical between limbs, whether the LT profile varies as a function of age or sex, and the efficacy of the LT profile technique remain unknown. The purpose of this study was to determine if there was a significant side-to-side length difference in the LT profile (LTD) according to age and sex., Methods: We attempted to determine the amount of medial prominence of the lesser trochanter relative to the medial cortex of the femoral shaft (the LT profile) using 3-dimensional computed tomography (3D-CT) images of normal femora obtained bilaterally (366 subjects) in anatomic positions. We also compared the left and right sides to determine the amount of natural asymmetry by age and sex. In addition, we compared the side-to-side difference in the LT version with the LTD to determine whether the LTD represented the difference in femoral rotation., Results: The LTD was <4 mm (meaning an LT version difference of <10°) in 83% of the subjects, but was ≥4 mm (an LT version difference of ≥10°) in 17%. Subset analysis demonstrated that the differences were greatest in women >70 years of age. The largest LTD (both sexes) was observed in individuals over 70 years of age (2.62 ± 1.37 mm, compared with <55 years: 1.55 ± 1.36 mm and 55 to 70 years: 2.27 ± 1.70 mm). There was no significant difference between sexes in the under-70 age groups. However, the LTD was significantly greater in women over 70 years than in men over 70 years (3.10 ± 1.42 versus 2.41 ± 1.30 mm)., Conclusions: Since the LTD demonstrated side-to-side symmetry within 4 mm, or 10° of rotation, in 83% of all subjects, we consider the LT profile to be useful as a guide to assess rotational reduction clinically. However, surgeons should recognize that, in 17% of cases, using this technique could result in malrotation of ≥10°. The rate of malrotation may be even higher in women over 70, for whom supplemental techniques to ensure correct rotation may be appropriate., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G679)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Coral concrete has low cost and convenient materials, making it an excellent raw material for processing. However, its lower strength limits the application of coral concrete. Surface modification is expected to increase the properties of porous coral concrete. In this study, single and compound modification treatments were applied to the surface of a coral aggregate to improve its properties for promoting the mechanical performance of coral concrete. The results showed that the micro-aggregate effect and pozzolanic activity of granulated blast furnace slag (GBFS) and the permeability and polycondensation of sodium silicate (SS) could be mutually promoted. The GBFS and SS could effectively fill the pores of the coral aggregate, enhancing the properties of the aggregate, such as density and load-bearing capacity, and reducing the water absorption and crushing index by more than 50%. GBFS and SS could intensify and accelerate the hydration of cement, and generate a large number of hard hydration products at the interfacial transition zone (ITZ), which could strengthen the bonding between the aggregate and mortar, improving the strength of the ITZ. The compressive strength of the coral concrete was significantly increased.

Piezoelectric actuators are widely used in the field of micro- and nanopositioning due to their high frequency response, high stiffness, and high resolution. However, piezoelectric actuators have hysteresis nonlinearity, which severely affects their positioning accuracy. As the driving frequency increases, the performance of piezoelectric actuators further degrades. In addition, the impact of force on piezoelectric actuators cannot be ignored in practical applications. Dynamic hysteresis with force-voltage coupling makes the hysteresis phenomenon more complicated when force and driving voltage are both applied to the piezoelectric actuator. Existing hysteresis models are complicated, or inaccurate in describing dynamic hysteresis with force-voltage coupling. To solve this problem, a force-voltage-coupled Prandtl-Ishlinskii (FVPI) model is proposed in this paper. First, the influence of driving frequency and dynamic force on the output displacement of the piezoelectric actuators are analyzed. Then, the accuracy of the FVPI model is verified through experiments. Finally, a force integrated direct inverse (F-DI) compensator based on the FVPI model is designed. The experimental results from this study show that the F-DI compensator can effectively suppress dynamic hysteresis with force-voltage coupling of piezoelectric actuators. This model can improve the positioning accuracy of piezoelectric actuators, thereby improving the working accuracy of the micro- or nano-operating system.

Silane coupling agent (SCA), a kind of organic solvent, was introduced to improve the performance of coral coarse aggregates and enhance the interfacial adhesion between the inorganic coral aggregate and the cement paste of coral concrete. The crushing indicator and water absorption of the coral aggregates over various dipping times were measured, and the slump, interface microhardness, and compressive strength of coral concrete tested. The microscopic appearances of the coral concrete before and after modification were analyzed based on SEM images. The experimental results indicate that SCA can effectively reduce the crushing indicator and water absorption of coral coarse aggregates, and the modification performance becomes better over time. SCA facilitates the generation of chemical forces between the coral aggregates and cement mortars, improves adhesion between the aggregates and mortars, augments the microhardness of the interface, and increases the compressive strength. According to the microscopic appearance of the treated and untreated coral aggregate interfaces, the aggregates and the mortars are in closer combination after modification.

Objective: To evaluate the effect of prepregnancy lymphocyte active immunotherapy on unexplained recurrent miscarriage, pregnancy success rate, and maternal-infant outcome., Methods: A total of 124 patients with recurrent miscarriage admitted to our hospital from January 2018 to December 2020 were selected as the research objects and divided into the experimental group and the control group according to the random number table method, with 62 patients in each group. The experimental group was treated with lymphocyte active immunotherapy, and the control group was given conventional treatment. The pregnancy success rate, estrogen indexes, hemorheology indexes, and psychological state of the two groups were compared., Results: The experimental group garnered a notably higher pregnancy success rate and a prominently lower miscarriage rate than the control group ( P < 0.05). Better results of self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were observed in the experimental group, as compared to the control group ( P < 0.05). The experimental group yielded more desirable results in terms of treatment satisfaction, estrogen indexes, and hemorheology indexes in comparison with the control group ( P < 0.05)., Conclusion: The use of lymphocyte active immunotherapy for patients with unexplained recurrent miscarriage can significantly increase the pregnancy success rate, optimize the maternal-infant outcome, drive down the miscarriage rate, and ameliorate the patient's estrogen levels and hemorheology indicators, which is worthy of promotion and application in clinical practice., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Junxia Li et al.)

Chronic inflammation affects bone metabolism and accelerates bone loss. This study is aimed at analyzing the prevalence of low bone mineral density (LBMD) in patients with untreated Takayasu's arteritis (TA) and risk factors. Forty untreated TA patients were enrolled, including 38 premenopausal women and 2 men before 50 years old. The control group included 60 age- and gender-matched healthy persons. Bone mineral density (BMD) of lumbar vertebrae and hip in patients with TA and the control group was measured by the dual-energy X-ray method. Serum 25OHD and β -CTX were also measured. The lumbar BMD of TA patients (0.89 ± 0.11 g/cm 2 ) was significantly lower than that of the healthy control (0.97 ± 0.11 g/cm 2 ). The prevalence of LBMD at the lumbar spine (17.50%) was significantly higher than that of the control group (3.33%). However, there was no significant difference at the hip. The 25OHD of TA patients was lower than that of healthy controls, while the level of β -CTX was higher. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in patients with LBMD were higher than those in patients with normal BMD. According to univariate correlation analysis, there was a significant negative correlation between LDL-C and lumbar BMD. Binary logistic regression analysis showed that LDL-C was an important factor affecting the occurrence of LBMD in patients with TA (OR = 25.269, P = 0.02). Our result reveals bone loss in TA patients, which hints the relationship among inflammation, lipid metabolism, and bone metabolism., Competing Interests: All authors declare that they have no competing interests, and all authors confirm its accuracy., (Copyright © 2021 Lingfei Mo et al.)

In this paper, an ultrahigh-strength marine concrete containing coral aggregates is developed. Concrete fabricated from marine sources is considered an effective and economical alternative for marine engineering and the construction of remote islands. To protect sea coral ecosystems, the coral aggregates used for construction are only efflorescent coral debris. To achieve the expected mechanical performance from the studied concrete, an optimal mixture design is conducted to determine the optimal proportions of components, in order to optimize the compressive strength. The mechanical properties and the autogenous shrinkage, as well as the heat flow of early hydration reactions, are measured. The hydration products fill up the pores of coral aggregates, endowing our concrete with flowability and self-compacting ability. The phases in the marine concrete are identified via X-ray diffraction analysis. The 28-day compressive and flexural strength of the developed marine concrete achieve 116.76 MPa and 18.24 MPa, respectively. On account of the lower cement content and the internal curing provided by coral aggregates, the volume change resulting from autogenous shrinkage is only 63.11% of that of ordinary reactive powder concrete.

Pressure sensors for wearable healthcare devices, particularly force sensitive resistors (FSRs) are widely used to monitor physiological signals and human motions. However, current FSRs are not suitable for integration into wearable platforms. This work presents a novel technique for developing textile FSRs (TFSRs) using a combination of inkjet printing of metal-organic decomposition silver inks and heat pressing for facile integration into textiles. The insulating void by a thermoplastic polyurethane (TPU) membrane between the top and bottom textile electrodes creates an architectured piezoresistive structure. The structure functions as a simple logic switch where under a threshold pressure the electrodes make contact to create conductive paths (on-state) and without pressure return to the prior insulated condition (off-state). The TFSR can be controlled by arranging the number of layers and hole diameters of the TPU spacer to specify a wide range of activation pressures from 4.9 kPa to 7.1 MPa. For a use-case scenario in wearable healthcare technologies, the TFSR connected with a readout circuit and a mobile app shows highly stable signal acquisition from finger movement. According to the on/off state of the TFSR with LED bulbs by different weights, it can be utilized as a textile switch showing tactile feedback., (© 2021 Wiley-VCH GmbH.)

Background: B-cell immunoglobulin repertoires with paired heavy and light chain can be determined by means of 10X single-cell V(D)J sequencing. Precise and quick analysis of 10X single-cell immunoglobulin repertoires remains a challenge owing to the high diversity of immunoglobulin repertoires and a lack of specialized software that can analyze such diverse data., Findings: In this study, specialized software for 10X single-cell immunoglobulin repertoire analysis was developed. SCIGA (Single-Cell Immunoglobulin Repertoire Analysis) is an easy-to-use pipeline that performs read trimming, immunoglobulin sequence assembly and annotation, heavy and light chain pairing, statistical analysis, visualization, and multiple sample integration analysis, which is all achieved by using a 1-line command. Then SCIGA was used to profile the single-cell immunoglobulin repertoires of 9 patients with coronavirus disease 2019 (COVID-19). Four neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were identified from these repertoires., Conclusions: SCIGA provides a complete and quick analysis for 10X single-cell V(D)J sequencing datasets. It can help researchers to interpret B-cell immunoglobulin repertoires with paired heavy and light chain., (© The Author(s) 2021. Published by Oxford University Press GigaScience.)

In this paper, six-layer AlN/Al gradient composites were prepared by a spark plasma sintering process to study the influences of sintering temperature and holding time on the microstructure and mechanical properties. The well-bonded interface enables the composite to exhibit excellent thermal and mechanical properties. The hardness and thermal expansion properties of the composite exhibit a gradient property. The hardness increased with the volume fraction of AlN while the CTE decreased as the volume fraction of AlN. The thermal expansion reaches the lowest value of 13-14 ppm/K, and the hardness reaches the maximum value of 1.25 GPa, when the target volume fraction of AlN is 45%. The simulation results show that this gradient material can effectively reduce the thermal stress caused by the mismatch of the thermal expansion coefficient as a transmitter and receiver (T/R) module. This paper attempts to provide experimental support for the preparation of gradient Al matrix composites.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge during the global pandemic and may facilitate escape from current antibody therapies and vaccine protection. Here we showed that the South African variant B.1.351 was the most resistant to current monoclonal antibodies and convalescent plasma from coronavirus disease 2019 (COVID-19)-infected individuals, followed by the Brazilian variant P.1 and the United Kingdom variant B.1.1.7. This resistance hierarchy corresponded with Y144del and 242-244del mutations in the N-terminal domain and K417N/T, E484K, and N501Y mutations in the receptor-binding domain (RBD) of SARS-CoV-2. Crystal structure analysis of the B.1.351 triple mutant (417N-484K-501Y) RBD complexed with the monoclonal antibody P2C-1F11 revealed the molecular basis for antibody neutralization and escape. B.1.351 and P.1 also acquired the ability to use mouse and mink ACE2 receptors for entry. Our results demonstrate major antigenic shifts and potential broadening of the host range for B.1.351 and P.1 variants, which poses serious challenges to current antibody therapies and vaccine protection., Competing Interests: Declaration of interests Patent applications have been filed on monoclonal antibodies targeting SARS-CoV-2 (patent application number: PCT/CN2020/108718; patent applicants: The Third People’s Hospital of Shenzhen and Tsinghua University). Q.Z., B.J., X.S., Z.Z., and L.Z. are the inventors. Q.Z., X.S., and L.Z. are shareholders of TSB Therapeutics., (Copyright © 2021 Elsevier Inc. All rights reserved.)