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Qingqing Xie,1 Caixia Sun,2 Zhenghua Fei,1 Xujing Yang1 1Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Nursing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Xujing YangDepartment of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, People’s Republic of ChinaEmail wzyyysj7979@126.comBackground: Tumor immunotherapy is a promising therapeutic strategy for patients with advanced cancers, and some tumors have profound and durable tumor regression. However, immunotherapy is still in the clinical trial stage with elusive long-term effects and complications as a new strategy. It is unclear whether patients possess an accurate understanding of the clinical benefits associated with these agents.Objective: To investigate the anxiety and depression of patients with advanced cancer who received immunotherapy using programmed death-1 or programmed death-ligand 1 after multiline treatment failure, explore the influencing factors, and provide a reference for clinical medical staff and psychological support for patients.Methods: The Hospital Anxiety and Depression Scale was used to calculate the anxiety and depression scores before and after 1, 2, and 3 courses of treatment, respectively. The patients with anxiety and depression were counted. Purposive sampling was used to conduct face-to-face semi-structured interviews with 21 patients to find out the reasons. The obtained data were analyzed and collated using Colaizzi’s phenomenological method.Results: One hundred and twenty-six patients with advanced cancers were included in the study. Before and after 1, 2 and 3 courses of treatment, 18.26%, 23.0%, 50% and 54% of patients suffered from anxiety and depression, respectively. The proportion of patients with anxiety and depression during immunotherapy kept increasing, mainly due to therapeutic efficacy below expectation, lack of timely information after treatment, lack of awareness of treatment and drugs, and lack of family and social support.Conclusion: Patients with advanced tumors after multiline treatment failure are susceptible to anxiety and depression during immunotherapy. It is necessary to test the emotional state of patients in time and carry out early intervention. Nursing staffs and medical staffs should adopt personalized measures to meet the psychological needs of patients.Keywords: anxiety, depression, cancer, immunotherapy, quality of life

A light-driven redox deracemization to prepare optically pure cyclamines from their racemates is developed. This reaction provides a wide range of chiral indolines and tetrahydroquinolines with high yields and enantioselectivities.

STUDY QUESTION Do distinct subpopulations of decidual stromal cells (DSCs) exist and if so, are given subpopulations enriched in recurrent miscarriage (RM)? SUMMARY ANSWER Three subpopulations of DSCs were identified from which inflammatory DSCs (iDSCs) and glycolytic DSCs (glyDSCs) are significantly enriched in RM, with implicated roles in driving decidual inflammation and immune dysregulation. WHAT IS KNOWN ALREADY DSCs play crucial roles in establishing and maintaining a successful pregnancy; dysfunction of DSCs has been considered as one of the key reasons for the development of RM. STUDY DESIGN, SIZE, DURATION We collected 15 early decidual samples from five healthy donors (HDs) and ten RM patients to perform single-cell RNA sequencing (scRNA-seq). A total of 43 RM patients and 37 HDs were enrolled in the validation cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS Non-immune cells and immune cells of decidual tissues were sorted by flow cytometry to perform scRNA-seq. We used tissue microarrays (TMA) to validate three distinct subpopulations of DSCs. The expression of inflammatory and glycolytic proteins by DSCs was validated by immunohistochemistry (IHC) and multiplex immunohistochemistry (mIHC). Different subsets of decidual NK (dNK) cells and macrophages were also validated by multicolor flow cytometry and mIHC. Cell ligand–receptor and spatial analyses between DSCs and immune cells were analyzed by mIHC. MAIN RESULTS AND THE ROLE OF CHANCE We classify the DSCs into three subtypes based on scRNA-seq data: myofibroblastic (myDSCs), inflammatory (iDSCs) and glycolytic (glyDSCs), with the latter two being significantly enriched in RM patients. The distribution patterns of DSC subtypes in the RM and HD groups were validated by mIHC. Single-cell analyses indicate that the differentiation of iDSCs and glyDSCs may be coupled with the degrees of hypoxia. Consequently, we propose a pathological model in which a vicious circle is formed and fueled by hypoxic stress, uncontrolled inflammation and aberrant glycolysis. Furthermore, our results show that the inflammatory SPP1+ macrophages and CD18+ dNK cells are preferentially increased in the decidua of RM patients. Cell ligand–receptor and mIHC spatial analyses uncovered close interactions between pathogenic DSCs and inflammatory SPP1+ macrophages and CD18+ NK cells in RM patients. LARGE SCALE DATA The raw single-cell sequence data reported in this paper were deposited at the National Omics Data Encyclopedia (www.biosino.org), under the accession number OEP002901. LIMITATIONS, REASONS FOR CAUTION The number of decidual samples for scRNA-seq was limited and in-depth functional studies on DSCs are warranted in future studies. WIDER IMPLICATIONS OF THE FINDINGS Identification of three DSC subpopulations opens new avenues for further investigation of their roles in RM patients. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Strategic Priority Research Program (No. XDB29030302), Frontier Science Key Research Project (QYZDB-SSW-SMC036), Chinese Academy of Sciences; National Key Research and Development Program of China (2021YFE0200600), National Natural Science Foundation of China (No. 31770960), Shanghai Municipal Science and Technology Major Project (No. 2019SHZDZX02, HS2021SHZX001), and Shanghai Committee of Science and Technology (17411967800). All authors report no conflict of interest.

STUDY QUESTION Can new genetic factors responsible for male infertility be identified, especially for those characterized by asthenospermia despite normal sperm morphology? SUMMARY ANSWER We identified the novel pathogenetic gene IQ motif and ubiquitin-like domain-containing (IQUB) as responsible for male infertility characterized by asthenospermia, involving sperm radial spoke defects. WHAT IS KNOWN ALREADY To date, only a few genes have been found to be responsible for asthenospermia with normal sperm morphology. Iqub, encoding the IQUB protein, is highly and specifically expressed in murine testes and interacts with the proteins radial spoke head 3 (RSPH3), CEP295 N-terminal like (CEP295NL or DDC8), glutathione S-transferase mu 1 (GSTM1) and outer dense fiber of sperm tails 1 (ODF1) in the yeast two-hybrid system. STUDY DESIGN, SIZE, DURATION The IQUB variant was identified by whole-exome sequencing in a cohort of 126 male infertility patients with typical asthenospermia recruited between 2015 and 2020. Knockout (KO) and knockin (KI) mouse models, scanning and transmission electron microscopy (TEM), and other functional assays were performed, between 2019 and 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS The IQUB variant was identified by whole-exome sequencing and confirmed by Sanger sequencing. Iqub KO and KI mice were constructed to mimic the phenotype of the affected individual. After recapitulating the phenotype of human male infertility, scanning and TEM were performed to check the ultrastructure of the sperm. Western blot and co-immunoprecipitation were performed to clarify the pathological mechanism of the IQUB variant. MAIN RESULTS AND THE ROLE OF CHANCE We identified a homozygous nonsense IQUB variant (NM_001282855.2:c.942T> G(p.Tyr314*)) from an infertile male. Iqub KO and KI mice mimicked the infertility phenotype and confirmed IQUB to be the pathogenetic gene. Scanning and TEM showed that sperm of both the mouse models and the affected individual had radial spoke defects. The functional assay suggested that IQUB may recruit calmodulin in lower Ca2+ environments to facilitate the normal assembly of radial spokes by inhibiting the activity of RSPH3/p-ERK1/2 (a nontypical AKAP (A-Kinase Anchoring Protein) forming by RSPH3 and phosphorylation of extracellular signal-regulated kinase 1 and 2 (p-ERK1/2)). LIMITATIONS, REASONS FOR CAUTION Additional cases are needed to confirm the genetic contribution of IQUB variants to male infertility. In addition, because no IQUB antibody is available for immunofluorescence and the polyclonal antibody we generated was only effective in western blotting, immunostaining for IQUB was not performed in this study. Therefore, this study lacks direct in vivo proof to confirm the effect of the variant on IQUB protein level. WIDER IMPLICATIONS OF THE FINDINGS Our results suggest a causal relation between IQUB variants and male infertility owing to asthenospermia, and partly clarify the pathological mechanism of IQUB variants. This expands our knowledge of the genes involved in human sperm asthenospermia and potentially provides a new genetic marker for male infertility. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Key Research and Development Program of China (2021YFC2700100), the National Natural Science Foundation of China (32130029, 82171643, 81971450, 82001538, and 81971382) and the Guangdong Science and Technology Department Guangdong-Hong Kong-Macao Joint Innovation Project (2020A0505140003). There are no competing interests to declare. TRIAL REGISTRATION NUMBER N/A.

In the case of low-rate peeling, an adhesive can undergo a large tensile deformation through the viscous flow and form the fingering pattern at the peeling interface, resulting in homogeneous stripes on the peeled surface. In the case of high-rate peeling, no larger viscous deformation occurs, and no surface patterns will be generated. However, it is still unclear how the surface pattern evolves when an adhesive is peeled from a relatively low rate to a high rate. Here, by peeling an adhesive tape at 180° over a wide range of rates, we find that the adhesive tape can undergo a steady peeling. As the peeling rate increases, it is observed that the surface pattern in the peeled adhesive tape tends to evolve from the initial striped pattern to a crescent pattern, then to a spotted pattern. Even in the case of the stick-slip peeling at a small angle, the patterned region also presents the same evolutionary trend. By exploiting a high-speed camera to track the deformation process of the adhesive, it is found that this evolution is actually driven by the cohesive failure of the peeling adhesive. We describe the failure process, revealing the formation mechanism of the crescent pattern. We also discuss the effect of the peeling rate on the interface instability morphology by combining the finite element simulations, elucidating how the surface pattern evolves with the peeling rate.

To construct a predictive nomogram of the risk of nosocomial infections among patients after cardiac valve replacement surgery.Nosocomial infections are a standout challenge that worsens the prognosis of patients after valve replacement surgery. However, studies on the nomogram of nosocomial infections in these patients have remained scarce.A retrospective cohort study.Patients (n = 720) following valve replacement surgery from 2018 to 2019 were selected. LASSO regression and multivariate logistic regression were utilised to ascertain predictors of nosocomial infections. The predictive performance of the nomogram was appraised by calibration and discrimination. Decision and impact curves were used to assess the clinical utility. Internal validation was implemented via 1000 bootstrap samples to mitigate overfitting. TRIPOD guidelines were used in this study.One hundred and fifty one patients (20.97%) experienced nosocomial infections following valve replacement surgery. Heart failure, preoperative anaemia, valve material, American Society of Anesthesiologists score ≥ IV, prolonged duration of surgery, duration of mechanical ventilation ≥ 24 h and indwelling nasogastric tube were predictors of nosocomial infections. Using these variables, we developed a predictive nomogram of the occurrence of nosocomial infections and the internal validation results demonstrated good discrimination and calibration of the nomogram. The clinical decision and impact curve revealed significant clinical utility.The present study constructed a nomogram for predicting the risk of nosocomial infections in patients following cardiac valve replacement surgery. This nomogram may strengthen the effective screening of patients at high risk of nosocomial infections.This risk warning tool can assist clinical staff in making decisions and providing individualised infection control measures for patients, which has a significant reference value for clinical practice.The data for this study were obtained from the hospital database, and the entire process of the study did not involve patient participation.

Low-cost surfactants are of great importance for many applications. Chitosan is one of the abundant promising candidates as a raw material for low-cost surfactants. However, how to tune the molecular structure to achieve high solubility, low surface tension, and good foam stability is a great challenge. Herein, the ‘comb-like’ zwitterionic polymer surfactant based on chitosan by partial N-alkylation and quaternization was prepared. The experimental results demonstrate that the length and degree of substitution of the alkyl chain have a significant influence on the properties of the products. Such comb-type zwitterionic polymer surfactants have good water solubility, and the water solubility can reach up to 85 g/L. Surface tension and foam performance tests reveal that such ‘comb-like’ zwitterionic polymer surfactants have excellent surface activity and good foam stability, especially for the products with a degree of substitution of 20%; their surface tension can be as low as 27.1 mN/m, and the foam stability can be improved by 59.32%.

Introduction: Insulin has an effect on neurodegenerative diseases. However, the role and mechanism of insulin in vascular dementia (VD) and its underlying mechanism are unknown. In this study, we aimed to investigate the effects and mechanism of insulin on VD.Methods: Experimental rats were randomly assigned to control (CK), Sham, VD, and insulin (INS) + VD groups. Insulin was administered by intranasal spray. Cognitive function was evaluated using the Morris's water maze. Nissl's staining and immunohistochemical staining were used to assess morphological alterations. Apoptosis was evaluated using TUNEL-staining. Transcriptome and metabolome analyses were performed to identify differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs), respectively.Results: Insulin significantly improved cognitive and memory functions in VD model rats (p < 0.05). Compared with the VD group, the insulin + VD group exhibited significantly reduced the number of Nissl's bodies numbers, apoptosis level, GFAP-positive cell numbers, apoptosis rates, and p-tau and tau levels in the hippocampal CA1 region (p < 0.05). Transcriptomic analysis found 1,257 and 938 DEGs in the VD vs. CK and insulin + VD vs. VD comparisons, respectively. The DEGs were mainly enriched in calcium signaling, cAMP signaling, axon guidance, and glutamatergic synapse signaling pathways. In addition, metabolomic analysis identified 1 and 14 DEMs between groups in negative and positive modes, respectively. KEGG pathway analysis indicated that DEGs and DEMs were mostly enriched in metabolic pathway.Conclusion: Insulin could effectively improve cognitive function in VD model rats by downregulating tau and p-tau expression, inhibiting astrocyte inflammation and neuron apoptosis, and regulating genes involved in calcium signaling, cAMP signaling, axon guidance, and glutamatergic synapse pathways, as well as metabolites involved in metabolic pathway.

BackgroundObesity is a common and highly convincing risk factor for many cancers, including liver cancer. Sex disparities in the body composition and regulatory mechanisms involved in energy homeostasis may contribute to the difference in the incidence of cancer. However, evidence on the gender-specific association between body composition and liver cancer incidence is limited. We performed this study to investigate the linear and non-linear associations of body composition with liver cancer risk by gender.Materials and methodsThis prospective analysis included 4,75,659 participants free of cancer, based on the UK Biobank. We used Cox proportional hazard models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for potential confounders. Restricted cubic spline was performed to investigate the potential non-linear associations.ResultsDuring a median follow-up, 275 cases (174 male patients and 101 female patients) of liver cancer were identified. Male patients in the highest body fat percentage group are more likely to develop liver cancer (HR = 1.89, 95% CI: 1.17–3.03) compared with those in the lowest group. The one-unit increase of whole-body fat mass, arm fat mass, and trunk fat mass was associated with 1.03-, 1.14-, and 1.05-fold increased risk of liver cancer in male subjects, respectively. U-shaped associations of body composition with liver cancer risk were observed in the female subjects. Both high and low levels of whole-body fat-free mass, particularly in the arm and trunk, were associated with an increased risk of liver cancer.ConclusionThis study found a gender-specific association between body composition and liver cancer risk and provided evidence for individualized weight management for the prevention of liver cancer.

Ultracompact chip-integrated single-photon sources of collimated beams with polarizationencoded states are crucial for integrated quantum technologies. However, most of currently available single-photon sources rely on external bulky optical components to shape the polarization and phase front of emitted photon beams. Efficient integration of quantum emitters with beam shaping and polarization encoding functionalities remains so far elusive. Here, we present ultracompact single-photon sources of linearly polarized vortex beams based on chip-integrated quantum emitter-coupled metasurfaces, which are meticulously designed by fully exploiting the potential of nanobrick arrayed metasurfaces. We first demonstrate on-chip single-photon generation of high-purity linearly polarized vortex beams with prescribed topological charges of -1, 0, and +1. We further realize multiplexing of single-photon emission channels with orthogonal linear polarizations carrying different topological charges and demonstrate their entanglement. Our work illustrates the potential and feasibility of ultracompact quantum emitter-coupled metasurfaces as a new quantum optics platform for realizing chip-integrated high-dimensional single-photon sources., 17 pages and 4 figures in the main text; 22 pages and 14 figures in supplementary information

Viral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn’t. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.

In the federated learning scenario, geographically distributed clients collaboratively train a global model. Data heterogeneity among clients significantly results in inconsistent model updates, which evidently slow down model convergence. To alleviate this issue, many methods employ regularization terms to narrow the discrepancy between client-side local models and the server-side global model. However, these methods impose limitations on the ability to explore superior local models and ignore the valuable information in historical models. Besides, although the up-to-date representation method simultaneously concerns the global and historical local models, it suffers from unbearable computation cost. To accelerate convergence with low resource consumption, we innovatively propose a model regularization method named FedTrip, which is designed to restrict global-local divergence and decrease current-historical correlation for alleviating the negative effects derived from data heterogeneity. FedTrip helps the current local model to be close to the global model while keeping away from historical local models, which contributes to guaranteeing the consistency of local updates among clients and efficiently exploring superior local models with negligible additional computation cost on attaching operations. Empirically, we demonstrate the superiority of FedTrip via extensive evaluations. To achieve the target accuracy, FedTrip outperforms the state-of-the-art baselines in terms of significantly reducing the total overhead of client-server communication and local computation., 11 pages, to be published in the 2023 IEEE International Parallel and Distributed Processing Symposium (IPDPS)

L-ribulose, a kind of high-value rare sugar, could be utilized to manufacture L-form sugars and antiviral drugs, generally produced from L-arabinose as a substrate. However, the production of L-ribulose from L-arabinose is limited by the equilibrium ratio of the catalytic reaction, hence, it is necessary to explore a new biological enzymatic method to produce L-ribulose. Ribose-5-phosphate isomerase (Rpi) is an enzyme that can catalyze the reversible isomerization between L-ribose and L-ribulose, which is of great significance for the preparation of L-ribulose. In order to obtain highly active ribose-5-phosphate isomerase to manufacture L-ribulose, ribose-5-phosphate isomerase A (OsRpiA) from Ochrobactrum sp. CSL1 was engineered based on structural and sequence analyses. Through a rational design strategy, a triple-mutant strain A10T/T32S/G101N with 160% activity was acquired. The enzymatic properties of the mutant were systematically investigated, and the optimum conditions were characterized to achieve the maximum yield of L-ribulose. Kinetic analysis clarified that the A10T/T32S/G101N mutant had a stronger affinity for the substrate and increased catalytic efficiency. Furthermore, molecular dynamics simulations indicated that the binding of the substrate to A10T/T32S/G101N was more stable than that of wild type. The shorter distance between the catalytic residues of A10T/T32S/G101N and L-ribose illuminated the increased activity. Overall, the present study provided a solid basis for demonstrating the complex functions of crucial residues in RpiAs as well as in rare sugar preparation.

The purpose of this study was to clarify the differences in the diagnosis and treatment outcomes between radioactive iodine-induced sialadenitis (RAIS) and chronic obstructive parotitis (COP). The study cohort comprised 47 consecutive patients diagnosed with RAIS and 50 patients with COP. All patients were treated by interventional endoscopy. Clinical, sialography, and endoscopy characteristics and treatment outcomes were compared between the two groups. Compared with the COP group, the RAIS group included more females (male:female ratio 1:8.4 vs 1:2.1; P = 0.011) and had a younger onset age (42 vs 50 years; P = 0.001) and shorter disease duration prior to hospital visit (5.4 vs 34.8 months; P0.001). In the RAIS group, sialography revealed obliteration of the main duct (20.4% vs 0%; P0.001), non-visualization of the main gland (23.7% vs 0%; P0.001), and incomplete contrast filling of the main gland (19.4% vs 6.4%; P = 0.008), which were scarcely observed in the COP group. Endoscopy revealed a higher percentage of duct atresia in RAIS compared to COP (20.4% vs 0%; P0.001). During follow-up, a higher percentage of RAIS patients had duct atresia and gland atrophy (49.5% vs 1.1%, P0.001). Compared with COP, RAIS more commonly involves younger females and has a shorter disease duration. Atresia of the main duct and atrophy of the gland parenchyma occur more often despite the use of interventional endoscopy.

Available evidence is incomplete and inconsistent in the outcomes of heart failure (HF) patients with preserved ejection fraction (HFpEF), mildly reduced ejection fraction (HFmrEF), and reduced ejection fraction (HFrEF). There are also limited data on the proportions and long-term prognosis among the three HF phenotypes in China. We aimed to characterize the 5 year prognosis in three HF phenotypes according to EF in a cohort of hospitalized HF patients undergoing coronary angiography in southern China.Hospitalized patients with HF were enrolled from the Cardiorenal ImprovemeNt registry (CIN; ClinicalTrials.gov NCT04407936) between January 2007 and December 2014. HF phenotypes were defined as HFpEF (EF ≥ 50%), HFmrEF (EF 41-49%), and HFrEF (EF ≤ 40%). Kaplan-Meier and Cox proportional hazards models were constructed to examine differences in 5 year outcomes in HF patients with different phenotypes. A total of 4880 HF patients [mean age: 61.8 ± 10.3, male: 3156 (64.7%)] were included: 2768 (57%) had HFpEF, 1015 (21%) had HFmrEF, and 1097 (22%) had HFrEF. Patients with HFrEF were older than those with HFpEF (62.5 ± 10.6 vs. 61.3 ± 10.1, P 0.001) and more likely to be male (78.0% vs. 55.9%, P 0.001). With 5 year follow-up through the end of December 2019, 1624 (27.6%) patients died. Controlling confounding variables, declined EF category was independently associated with increased 5 year mortality {HFrEF 25.2% vs. HFpEF 13.4%, adjusted hazard ratio [aHR]: 1.85 [95% confidence interval (CI): 1.45 to 2.35]; HFmrEF 18.1% vs. HFpEF 13.4%, aHR: 1.40 [95% CI: 1.08 to 1.81]; HFrEF 25.2% vs. HFmrEF 18.1%, aHR: 1.32 [95% CI: 1.02 to 1.71]}.In this Chinese cohort, patients with HFrEF account for less than a fourth of HF patients. One-sixth individuals with HF died in 5 years. HFrEF was associated with a nearly two-fold increased risk of 5 year mortality than HFpEF. Further studies are needed to prospectively evaluate the efficacy of improving treatment on outcomes in all three HF phenotypes.

Successful pregnancy in humans requires adequate maternal-fetal immune tolerance. During regulatory T (Treg) cells play a key role. Sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) signaling represses Treg cell differentiation, but whether this relates to the process of recurrent pregnancy loss is still unclear.Treg cells in the placenta were examined using flow cytometry. The expression of sphingosine kinase-1 and -2(SPHK1 and SPHK2), two key kinases controlling S1P production, was detected in placenta samples from 36 patients with recurrent pregnancy loss (RPL) and 40 control participants using immunoblotting. The level of sphingosine-1-phosphate receptor-1 (S1PR1) in placental T cells was examined using RT-qPCR and immunoblotting. Cell surface S1PR1 levels were detected using flow cytometry. The interactions between miRNAs and S1PR1 mRNA were predicted using bioinformatics tools and were confirmed by dual luciferase assay and immunoblotting.RPL patients had fewer Treg cells (p = 0.034) in the placenta, especially TIM3+ Treg cells (p = 0.0076). S1PR1 protein levels were significantly increased in placental T cells of patients with RPL (p = 0.0065). MiR-33a, miR-33b, and miR-181a were reduced in the placenta from patients with RPL, which were identified to repress S1PR1 expression by targeting the 3'UTR. Knockdown of miR-33a, miR-33b and miR-181a in human naïve T cells inhibits Treg cell differentiation by upregulating S1PR1 in vitro.This study, for the first time, successfully constructed the correlation between dysregulated miRNAs in placenta and RPL, which partially unveiled the etiology of RPL and provided a therapeutic potential for RPL treatment.

CRISPR-Cas9 is a common tool for gene editing, and appropriate sgRNAs are the key factor for successful editing. In this study, the effect of sgRNA length and number on editing efficiency was analyzed in rice using CYP81A6 as the target gene. A series of CRISPR-Cas9 plant expression vectors containing single sgRNAs with different lengths (17, 18, 19, 20, 21, 22, 23 nt) or two sgRNAs were constructed and introduced into rice cultivar Zhonghua11 by Agrobacterium-mediated transformation. Analysis of the editing status of 1283 transgenic rice plants showed that 371 were successfully edited with base preference. Single A or T insertions were the most frequent among the six edited types. The editing efficiency of transgenic rice with two sgRNAs was higher than that with a single sgRNA. Editing efficiency and sgRNA length showed a normal distribution with 20 nt sgRNA (25%) being the most efficient. The editing efficiency decreased slightly with decreases of 1–2 bases (19 nt 20%, 18 nt 21%), but decreased significantly with a decrease of 3 bases (17 nt 4.5%). Editing efficiency was significantly reduced by adding 1 to 3 bases (21 nt 16.8%, 22 nt 13%, 23 nt 13%) to the sgRNA. These results provide data for successful gene editing or rice by CRISPR-Cas9.

High-efficient machining of SiC particles reinforced composites is always challenging mainly due to their poor surface integrity. In this study, a two-phase finite element model including the Al alloy matrix with Johnson-Cook model and SiC particle with elastic-brittle failure model were developed. The main purpose is to comprehensively investigate particle removal mechanisms and surface integrity following simulation and experimental studies on milling SiCp/Al composites. Specifically, the distributions of residual stress along the depth direction were predicted using finite element model. Results indicated that compressive residual stress mainly appeared on the machined surface, while tensile residual stress distributed at deeper depth down to 0.02 mm. Besides, different relative positions between tool and particle induced specific particle removal modes, which eventually led to various surface defects. Higher level of cutting speed (180 m/min) and feed rate (0.09 mm/tooth) aggravated surface defects and increased the thickness of broken-SiC layer in subsurface. The simulated machined surface defects and surface residual stress correlated well with the experimental observation, and the maximum error value of cutting force was less than 15%. The proposed finite element model was efficient to predict cutting force and distribution of residual stress along the depth direction.

It is challenging to investigate fast supramolecular processes due to the lack of appropriate characterization methods with high structural resolution. In thisstudy, microfluidic nuclear magnetic resonance (μFNMR) spectroscopy was employed to monitor the kinetics of threading and dethreading of a pseudo[6]rotaxane system. By employing high time resolution μF-NMR, 1H and two-dimensional (2D) rotating frame nuclear Overhauser effect spectroscopy (ROESY) NMR spectra were recorded at any timepoint within 1.5 s after the onset of the process. This technique enabled the successful identification of kinetic intermediates and rate-determining steps,usually impossible to determine by other spectroscopic techniques. Thus, our study demonstrates the capability of μF-NMR in investigating the mechanismof complex supramolecular systems.

A broadband wide-angle scanning array antenna with suppressed mutual coupling for 5G Sub-6G mobile communication applications is presented in this letter. To reduce mutual coupling, the metal columns are used in the dipole array antenna. The metal columns are positioned below the edge of the dipole, leading to the improved the impedance matching characteristics and a wider scanning angle. A 18 prototype of the suggested design has been manufactured and tested to ensure its usefulness. The overall dimension is 2.3300.2800.240 (0 is the free space wavelength at 2.5 GHz). The measured and simulated results are quite consistent. The main lobe achieves a scanning range of 60 at 2.5-4.5 GHz (57.1%, active VSWR

Kinetic control over structures and functions of complex assembly systems has aroused widespread interest. Understanding the complex pathway and transient intermediates is helpful to decipher how multiple components evolve into complex assemblies. However, for supramolecular polymerizations, thorough and quantitative kinetic analysis is often overlooked. Challenges remain in collecting the information of structure and content of transient intermediates

The full utilization of adsorption sites is crucial for adsorption technology. Metal-organic frameworks (MOFs), which are hot spot materials in environmental remediation, are not satisfied in many cases for their high specific surface area and relatively low adsorption capacity. In this work, a series of zirconium-iron bimetallic MOFs (ZrxFe(1-x)-MOF-808) was prepared. The optimal material (Zr0.8Fe0.2-MOF-808) possesses a superb adsorption capacity of 524 and 310 mg g–1 for antimonate and antimonite, respectively. The carboxyl and hydroxyl groups were identified as the main adsorption sites by FTIR and XPS. The role of Fe in the adsorption process of Zr0.8Fe0.2-MOF-808 were further explored by DFT simulations, four binding manners were discovered and consistent with the adsorption capacity data. Subsequently, the application potential tests proved that the Zr0.8Fe0.2-MOF-808 shows good anti-interference ability, wide pH adaptability, and recyclability. Overall, this high-performance bimetallic MOF has been analyzed from the macrocosm to microcosmic, which provides a certain support for the development of MOFs modification.

Background: The anti-PP1Pk antibody is a rare antibody associated with recurrent spontaneous abortion (RSA) in the first trimester. As it is a rare entity, few reports have been published, especially in China. Currently, there is no specific treatment for RSA associated with anti-PP1Pk antibody because it is a naturally occurring antibody. This study aims to report three cases of RSA associated with the anti-PP1Pk antibody to share our experiences with its management. Methods: The three patients' medical information was obtained from the medical records. Intravenous immunoglobulin and/or plasmapheresis was offered to the patients. We also made an extension research of the related literature about RSA associated with anti-PP1Pk antibody. Results: Although patients received intervention, the maternal anti-PP1Pk antibody titer remained stable and did not decrease. There were no live births. We summarized publications about pregnancy in women with anti-PP1Pk antibodies. Conclusions: Early initiation of plasmapheresis in high-risk patients with anti-PP1Pk antibodies should be strongly considered.

In this paper, we propose a Fuzzy Window with the Gaussian Processed Label (FW-GPL) method to mitigate the overlap problem in the neighboring ordinal category when scoring images. Many published conventional methods treat this challenge as a traditional regression problem and make a strong assumption that each ordinal category owns an adequate intrinsic rank to outline its distribution. Our FW-GPL method aims to refine the ordinal label pattern by using two novel techniques: (1) assembling fuzzy logic to the fully connected layer of convolution neural networks and (2) transforming the ordinal labels with a Gaussian process. Specifically, it incorporates a heuristic fuzzy logic from the ordinal characteristic and simultaneously plugs in ordinal distribution shapes that penalize the difference between the targeted label and its neighbors to ensure a concentrated regional distribution. Accordingly, the function of these proposed windows is leveraged to minimize the influence of majority classes that mislead the prediction of minority samples. Our model is specifically designed to carefully avoid partially missing continuous facial-age segments. It can perform competitively when using the whole continuous facial-age dataset. Extensive experimental results on three facial-aging datasets and one ambiguous medical dataset demonstrate that our FW-GPL can achieve compelling performance results compared to the State-Of-The-Art (SOTA).

Some cases of chronic rhinosinusitis (CRS) require surgical treatment and postoperative nasal packing, but bleeding and adhesion are common complications after nasal surgery. Biodegradable drug-loaded implants hold great therapeutic options for the treatment of CRS, but little data are available regarding the properties and effects of a novel drug-loaded haemostatic sponge (DLHS) in the nasal cavity and sinus. In this study, in vitro and in vivo experiments were used to test the physicochemical properties and investigate the biocompatibility and effectiveness of DLHS. The results showed that DLHSs present outstanding porosity and liquid absorption capacity, which might enhance their haemostatic ability, and they possess sustained-release ability for drugs. Further clinical trials confirmed their clinical efficacy and safety, and there was no evidence of adrenal cortical suppression. This study demonstrates the safety and efficacy of a novel biodegradable drug-loaded sponge with the possibility of being used in CRS patients, and this sponge may reduce inflammation and minimize adhesions via controlled local drug delivery without measurable systemic exposure.

The coexistence of mcr-1 and blaNDM-5 in the plasmid of Escherichia coli has been widely reported and such strains have been mainly isolated from animal and human feces. However, few reports have focused on the genetic diversity of mcr-1-carrying chromosomes and blaNDM-5-carrying plasmids in E. coli isolates from lesion-bearing animal organs. This study investigated the genetic characteristics of chromosome-mediated mcr-1 and plasmid-mediated blaNDM-5 in E. coli isolated from lesion-bearing animal organs. Nine mcr-1- and blaNDM-5-positive E. coli strains (MNPECs) showed extensive drug resistance (XDR). The predominant clonal complexes (CC) mainly belonged to CC156, CC10, and CC165 from the 56 MNEPCs (including nine strains in this study) retrieved from the literature. These strains were widely distributed in China, and originated from pig fecal samples, human stool/urine samples as well as intestinal contents of chicken. Two transconjugants harboring blaNDM-5 gene were also successfully obtained from two donors (J-8 and N-14) and this transfer increased the MIC for meropenem by 256 times. However, conjugative transfer of mcr-1 gene failed. Both J-8 and N-14 strains contained point mutations associated with quinolone resistance and more than three types of AMR genes, including the mcr-1 gene on the chromosome and the blaNDM-5 gene on the IncX3-type plasmid. The genetic structure of mcr-1 located on the chromosome was an intact Tn6330, and blaNDM-5-carrying IncX3-type plasmid was ISAb125-IS5-blaNDM-5-bleO-trpF-tat-cutA-IS26 gene cassette. Moreover, differences between chromosomes included additional partial sequence of phage integrated into host genome and the different genes associated with O-antigen synthesis.

In this investigation, Al–Cu alloy was used for wire-arc additive manufacturing experiment with and without assisted longitudinal magnetic field (ALMF) introduced, subsequently, heat treatment was conducted, aiming to investigate the variations of the improved characteristics brought by ALMF on microstructure and mechanical properties after heat-treated. The results indicated that the improved pores condition brought by ALMF was greatly weakened after heat-treated, while the promotion for the columnar to equiaxed transition and the improvement to precipitation remained. As for mechanical properties, the improvement of the uniform distribution of microhardness by the ALMF deteriorated. Moreover, the optimisation brought by ALMF on reducing the anisotropy of tensile strength was greatly weakened, and the improvement of elongation disappeared.