NK-derived exosome miR-1249-3p inhibits Mycobacterium tuberculosis survival in macrophages by targeting SKOR1.

Murine Natural Killer cells were cultivated in vitro to isolate NK-derived exosomes. Subsequent quantification via qPCR confirmed enrichment of miR-1249-3p. Ana-1 murine macrophages were cultured in vitro and subsequently inoculated with Mycobacterium tuberculosis (MTB) strain H37Rv. NK-exo and NK-exo miR-1249-3p were separately applied to the infection model, followed by immunological assays conducted post-48-hour co-culture. Western blot analyses corroborated that NK-exo exhibited exosomal marker proteins Granzyme A (GzmA), Granzyme B (GzmB), and Perforin (PFN), alongside a notable enrichment of miR-1249-3p. Functionally, NK-exo augmented the expression levels of Caspase-9,-8, and -3, as well as PARP, while attenuating the expression of NLRP3, ASC, and Cleaved-Caspase-1. Furthermore, qPCR demonstrated an up-regulation of Caspase-9, -8, and -3, along with pro-apoptotic factors Bax and Bid, and a concomitant down-regulation of the anti-apoptotic factor Bcl-2. The expression levels of inflammatory markers ASC, NLRP3, Cleaved-Caspase-1, and IL-1ß were concomitantly decreased. ELISA findings indicated diminished levels of TNF-α and ROS secretion. NK-exo miR-1249-3p specifically targeted and attenuated the expression of SKOR-1, engendering up-regulation of apoptosis-associated proteins and down-regulation of inflammation-related proteins, consequently affecting cellular fate.Our empirical evidence substantiates that NK-exo induces macrophage apoptosis, thereby mitigating MTB survival. Furthermore, NK-exo miR-1249-3p directly targets and inhibits SKOR-1 expression, leading to macrophage apoptosis and consequently hampering the proliferation of MTB. The data implicate the potential therapeutic relevance of NK-exo and miR-1249-3p in managing drug-resistant tuberculosis.

Evaluating health-related quality of life and subjective wellbeing among infertility patients: a cross-sectional study in mainland China.

PURPOSE: This study aimed to explore the health-related quality of life (HRQoL) and subjective wellbeing (SWB) of infertility patients in mainland China and to investigate the relationships between HRQoL and SWB instruments in infertility patients. METHODS: We conducted this cross-sectional study in the Hospital for Reproductive Medicine Affiliated of Shandong University between April 2019 and November 2019. Participants self-completed the five-level EQ-5D (EQ-5D-5L) questionnaire, the Assessment of Quality of Life (AQoL)-8D, and the WHO-5 wellbeing index (WHO-5). The agreements between EQ-5D-5L and AQoL-8D were assessed employing intraclass correlation coefficient (ICC) and Bland-Altman plots. Exploratory factor analysis (EFA) was conducted to examine the difference in descriptive systems among the three instruments. RESULTS: We analyzed a valid sample of 618 infertility patients (84.4%). The mean scores of the total EQ-5D-5L, AQoL-8D, and WHO-5 were 0.96 (95%CI 0.96, 0.96), 0.80 (95%CI 0.79, 0.81), and 16.92 (95%CI 16.52, 17.31), respectively. Patients diagnosed with primary infertility had significantly lower HRQoL and SWB than those with secondary infertility. The ICC of EQ-5D-5L and AQoL-8D was 0.14. The AQoL-8D (r = 0.625) was more strongly correlated with WHO-5 than with the EQ-5D-5L (r = 0.262). The EFA results indicated that HRQoL instruments and the WHO-5 instruments were complementary rather than substitutable. CONCLUSIONS: Poorer HRQoL and SWB were found that primary than secondary infertility patients. There exists a poor agreement between EQ-5D-5L and AQoL-8D and the difference in the psychosocial components may explain the difference. Measuring both HRQoL and SWB could provide complementary information for infertility patients.

The complete mitochondrial genome of Morishitium polonicum (Trematoda, Cyclocoelidae) and its phylogenetic implications.

Trematodes can adversely impact the health and survival of wild animals. The trematode family Cyclocoelidae, which includes large digenean bird parasites, lacks molecular analysis, and reclassifications have not been supported. This study produced the first fully assembled and annotated mitochondrial genome sequence for the trematode Morishitium polonicum. The whole length of the M. polonicum (GenBank accession number: OP930879) mitogenome is 14083 bp, containing 22 transfer ribonucleic acids (tRNAs), 2 ribosomal RNAs (rRNAs, rrnL and rrnS), and a noncoding control section (D-loop) 13777 to 13854 bp in length. The 12 PCG areas have 3269 codons and a total length of 10053 bp, which makes up 71.38% of the mitochondrial genome's overall sequence. Most (10/12) of the PCGs that code for proteins begin with ATG, while the nad4L and nad1 genes have a GTG start codon. Phylogenetic analysis using the concatenated nucleotide sequences of 12 PCGs, and the ML tree analysis results showed that M. polonicum is more closely related to with Echinostomatidae and Fasciolidae, which indicates that the family Cyclocoelidae is more closely associated with Echinochasmidae. This study provides mtDNA information, and analysis of mitogenomic structure and evolution. Moreover, we aimed to understand the phylogenetic relationships of this fluke.

Development and validation of the health-related quality of life instrument for Chinese infertile couples: a mixed-methods study protocol.

BACKGROUND: Infertility and its treatment have negative impacts on a couple's marital relationship, sexual life, psychological state and interpersonal relationships, causing personal distress. Health-related quality of life (HRQoL) has become an important component of health outcomes. HRQoL instruments developed in western culture are not always appropriate for use in China due to cultural differences. Probably due to the unique concept of fertility in China, infertility patients can be looked down upon and the family may  feel shameful. This study aims to develop a HRQoL instrument for infertile couples based on the Chinese social and cultural setting. METHODS: Complementary mixed methods will be used to develop a new HRQoL instrument for Chinese infertile couples. The study consists of four stages: the first stage will involve a systematic review and qualitative interviews to construct draft candidate items. In the second stage, quantitative research [e.g., exploratory factor analysis (EFA), item response theory (IRT)] and cognitive interviews will be used for item selection. The third stage will be instrument validation, in which classical test theory (CTT) and IRT will be applied. In the final stage, the minimal clinically important difference (MCID) will be calculated by using distribution-based methods and anchor-based methods (e.g., logistic regression, receiver operating characteristic curve). DISCUSSION: The new HRQoL instrument for Chinese infertile couples will be developed, which will provide a standard and effective HRQoL instrument in clinical outcome assessment and health outcome measurement.

Identification of the Hub Genes and the Signaling Pathways in Human iPSC-Cardiomyocytes Infected by SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is an enveloped single-stranded RNA virus that can lead to respiratory symptoms and damage many organs such as heart, kidney, intestine, brain and liver. It has not been clearly documented whether myocardial injury is caused by direct infection of cardiomyocytes, lung injury, or other unknown mechanisms. The gene expression profile of GSE150392 was obtained from the Gene Expression Omnibus (GEO) database. The processing of high-throughput sequencing data and the screening of differentially expressed genes (DEGs) were implemented by R software. The R software was employed to analyze the Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The protein-protein interaction (PPI) network of the DEGs was constructed by the STRING website. The Cytoscape software was applied for the visualization of PPI network and the identification of hub genes. The statistical analysis was performed by the GraphPad Prism software to verify the hub genes. A total of 516 up-regulated genes and 191 down-regulated genes were screened out. The top 1 enrichment items of GO in biological process (BP), Cellular Component (CC), and Molecular Function (MF) were type I interferon signaling pathway, sarcomere, and receptor ligand activity, respectively. The top 10 enrichment pathways, including TNF signaling pathway, were identified by KEGG enrichment analysis. A PPI network was established, consisting of 613 nodes and 3,993 edges. The 12 hub genes were confirmed as statistically significant, which was verified by GSE151879 dataset. In conclusion, the hub genes of human iPSC-cardiomyocytes infected with SARS-CoV-2 were identified through bioinformatics analysis, which may be used as biomarkers for further research.

Artificial intelligence-based multi-objective optimization protocol for protein structure refinement.

MOTIVATION: Protein structure refinement is an important step of protein structure prediction. Existing approaches have generally used a single scoring function combined with Monte Carlo method or Molecular Dynamics algorithm. The one-dimension optimization of a single energy function may take the structure too far away without a constraint. The basic motivation of our study is to reduce the bias problem caused by minimizing only a single energy function due to the very diversity of different protein structures. RESULTS: We report a new Artificial Intelligence-based protein structure Refinement method called AIR. Its fundamental idea is to use multiple energy functions as multi-objectives in an effort to correct the potential inaccuracy from a single function. A multi-objective particle swarm optimization algorithm-based structure refinement is designed, where each structure is considered as a particle in the protocol. With the refinement iterations, the particles move around. The quality of particles in each iteration is evaluated by three energy functions, and the non-dominated particles are put into a set called Pareto set. After enough iteration times, particles from the Pareto set are screened and part of the top solutions are outputted as the final refined structures. The multi-objective energy function optimization strategy designed in the AIR protocol provides a different constraint view of the structure, by extending the one-dimension optimization to a new three-dimension space optimization driven by the multi-objective particle swarm optimization engine. Experimental results on CASP11, CASP12 refinement targets and blind tests in CASP 13 turn to be promising. AVAILABILITY AND IMPLEMENTATION: The AIR is available online at: www.csbio.sjtu.edu.cn/bioinf/AIR/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The altered immunological status of children conceived by assisted reproductive technology.

BACKGROUND: With the increased use of assisted reproductive technology (ART), assessing the potential health risks of children conceived on ART important to public health. Most research in this area has focused on the effects of ART on perinatal, metabolic, and oncological risks in children. Although an increased risk of immune-related diseases has been reported in children born after ART, there are no studies on the immunological status of these children. This study aimed to evaluate the impact of different embryo transfer methods and fertilization strategies on the immune status of the offspring. METHODS: A total of 69 children born to women treated with ART and a matched control group of 17 naturally conceived (NC) children, all aged from 3 to 6 years, were recruited in the reproductive hospital affiliated to Shandong University. The frequency of immune cells in the peripheral blood was assayed using flow cytometry; plasma cytokine levels were determined by multiplex cytokine immunoassay with human cytokine magnetic beads. RESULTS: Compared to children born after natural conception, children born after ART had elevated interferon-γ (IFN-γ) levels, regardless of embryo transfer and fertilization strategies. Children in the fresh-embryo transfer group had significantly higher IL-4 levels and a lower ratio of IFN-γ to IL-4 than those in the NC group ((P = 0.004, 10.41 ± 5.76 pg/mL vs 18.40 ± 7.01 pg/mL, P = 0.023, 1.00 ± 0.48 vs 0.67 ± 0.32, respectively). Similar results were shown in either the in vitro fertilization (IVF) group or the intra-cytoplasmic sperm injection (ICSI) group (P < 0.05 and P = 0.08 for IVF; P < 0.05 and P < 0.05 for ICSI, respectively). These alterations in IL-4 concentrations and the ratio of IFN-γ to IL-4 were statistically significantly correlated with supra-physical E2 (estradiol) levels on the day of hCG administration (R = 0.502, P = 0.017; R = - 0.537, P = 0.010, respectively). Consistently, the frozen embryo transfer did not result in alterations of these immune indicators in the offspring. Overall, there were no significant differences between the ART group and NC group in the frequencies of T cells, B cells, natural killer (NK) cells, CD4+T cells, CD8+T cells, T helper (TH)1 cells, TH17 cells, and regulatory T (Treg) cells and cytokine levels of IL-10 and IL-17a (all P > 0.05). CONCLUSIONS: Immunological alterations existed in children born after the use of ART. The elevated E2 levels before embryo implantation contributed to the increased IL-4 levels in children conceived by fresh embryo transfer. The assessment of immunological alteration is of importance to children conceived by ART for early monitoring and intervention.

Evaluation of lateral flow immunochromatographic assay for diagnostic accuracy of cryptococcosis.

BACKGROUND: Cryptococcus is a conditional pathogenic fungus causing cryptococcosis, which is one of the most serious fungal diseases faced by humans. Lateral flow immunochromatographic assay (LFA) is successfully applied to the rapid detection of cryptococcal antigens. METHODS: Studies were retrieved systematically from the Embase, PubMed, Web of Science, and Cochrane Library before July 2019. The quality of the studies was assessed by Review Manager 5.0 based on the Quality Assessment of Diagnostic Accuracy Study guidelines. The extracted data from the included studies were analyzed by Meta-DiSc 1.4. Stata 12.0 software was used to detect the publication bias. RESULTS: A total of 15 articles with 31 fourfold tables were adopted by inclusion and exclusion criteria. The merged sensitivity and specificity in serum were 0.98 and 0.98, respectively, and those in the cerebrospinal fluid were 0.99 and 0.99, respectively. CONCLUSIONS: Compared to the urine and other samples, LFA in serum and cerebrospinal fluid is favorable evidence for the diagnosis of cryptococcosis with high specificity and sensitivity.

The STAT3 inhibitor WP1066 synergizes with vorinostat to induce apoptosis of mantle cell lymphoma cells.

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) characterized by the translocation t (11; 14) (q13; q32). Drug resistance remains a formidable obstacle to treatment and the median survival for MCL patients is between 3 and 5 years. Thus, there is an urgent need to discover novel approaches to MCL therapy. The signal transducer and activation of transcription 3 (STAT3) has been found to be constitutively activated in several subtypes of MCL cell lines and MCL tumors. WP1066, a small-molecule inhibitor of STAT3, exerted antitumor activity in hematological and solid malignancies by inhibiting key survival and growth signaling pathways. In the present study, we evaluated the antiproliferative and proapoptotic activity of WP1066 combined with pan-histone deacetylase (HDAC) inhibitor vorinostat (SAHA) in a panel of MCL cell lines. In addition, potential mechanisms involved were also explored. The outcome showed that combination of WP1066 with SAHA resulted in synergistic growth inhibition and apoptosis induction in MCL cell lines in vitro. Furthermore, combination of WP1066 with SAHA inhibited the constitutive STAT3 activation and modulated mRNA expressions of anti- and pro-apoptotic genes. Our findings suggest that agents targeting the STAT3 pathway such as WP1066 may be useful therapeutic drugs for MCL when combined with SAHA.

[Study on effect of scutellarin in resisting liver fibrosis in rats].

Totally 80 rats were randomly divided into the control group, the model group, low, middle and high dose (25, 50, 100 mg x kg(-1)) scutellarin( SC) groups and the colchicine ( Col) group. Apart from the blank group, all of the remaining groups were intraperitoneally injected with 0.5 mL pig serum twice every week for consecutively 13 weeks and orally administered with the corresponding drugs since the 9th week. The blank group and the model group were orally given equal volume of normal saline once every for consecutively four weeks. After the experiment, efforts were made to detect the contents of alanine aminotransferase (ALT), aspertate aminotransferase (AST), albumin (ALB), total protein (TP), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN) and collagen type IV (CIV), collect liver tissues of fixed positions, observe the pathological changes through hematoxylin-eosin (HE) staining, conduct the pathological grading for liver fibrosis, determine the expressions of hepatic collagen type I and III (C I, C III) and calculate their color rendering index. Compared with the model group, low, middle and high dose (25, 50, 100 mg x kg(-1)) SC groups could decrease the contents of ALT, AST, TBIL, HA, LN, CIV, increase the contents of ALB, TP in serum and reduce the contents of C I, C III in liver tissues. In conclusion, scutellarin has a certain therapeutic effect on immune liver fibrosis in rats induced by pig serum.

Unraveling the allosteric inhibition mechanism of PTP1B by free energy calculation based on umbrella sampling.

Protein tyrosine phosphatase 1B (PTP1B) is a promising target for the treatment of obesity and type II diabetes. Allosteric inhibitors can stabilize an active conformation of PTP1B by hindering the conformational transition of the WPD loop of PTP1B from the open to the closed state. Here, the umbrella sampling molecular dynamics (MD) simulations were employed to compute the reaction path of the conformational transition of PTP1B, and the snapshots extracted from the MD trajectory were clustered into 58 conformational groups based on the key conformational parameter. Then, the impact of the conformational change of the WPD loop on the interactions between the allosteric site of PTP1B and an allosteric inhibitor BB3 was explored by using the MM/GBSA binding free energy calculations and free energy decomposition analysis. The simulation results show that the binding free energy of BB3 increases gradually from the open to the closed conformation of the WPD loop, providing the molecular mechanism of allosteric inhibition. Correlation analysis of the different energy terms indicates that the allosteric inhibitor with more negative van der Waals contribution cannot only exhibit stronger binding affinity but also hinder the swing of the WPD loop more effectively. Besides, it is found that the energy contribution of Lys292 in the α7 helix undergoes significant change, which reveals that Lys292 is not only the key residue for ligand binding but also plays an important role in hindering the conformational change of the WPD loop.

Complete mitogenomes characterization and phylogenetic analyses of Ceratophyllus anisus and Leptopsylla segnis.

Fleas are one of the most common ectoparasites in warm-blooded mammals and an important vector of zoonotic diseases with serious medical implications. We sequenced the complete mitochondrial genomes of Ceratophyllus anisus and Leptopsylla segnis for the first time using high-throughput sequencing and constructed phylogenetic relationships. We obtained double-stranded circular molecules of lengths 15,875 and 15,785 bp, respectively, consisting of 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs, and two control regions. AT-skew was negative in both C. anisus (-0.022) and L. segnis (-0.231), while GC-skew was positive in both (0.024/0.248), which produced significant differences in codon usage and amino acid composition. Thirteen PCGs encoding 3,617 and 3,711 codons, respectively, isoleucine and phenylalanine were used most frequently. The tRNA genes all form a typical secondary structure. Construction of phylogenetic trees based on Bayesian inference (BI) and maximum likelihood (ML) methods for PCGs. The results of this study provide new information for the mitochondrial genome database of fleas and support further taxonomic studies and population genetics of fleas.

Patient and clinician perspectives on shared decision-making in infertility treatment: A qualitative study.

OBJECTIVES: To explore the considerations and barriers to implementing shared decision-making (SDM) in infertility treatment among female infertility patients, their male spouses, and fertility clinicians. METHODS: Participants were recruited from a reproductive medicine hospital in China's Shandong Province using purposive sampling. One-on-one interviews were held with female infertility patients and their spouses. In addition, a focus group discussion was conducted with fertility clinicians. Data analysis was subjected to open, axial, and selective coding. RESULTS: Nineteen female infertility patients and 10 male spouses were interviewed one-on-one. Five clinicians participated in the focus group discussion. Most female patients wanted to participate in the decision-making process, and that spouses and fertility clinicians supported SDM. Furthermore, key barriers were identified from the perspectives of multiple stakeholders, including communication difficulties, psychological pressure on female patients, patient preferences, multiple treatment stages, male spousal participation, clinician-patient trust, and subjective patient factors. CONCLUSIONS/PRACTICE IMPLICATIONS: This study explored the considerations of and barriers to implementing SDM in infertility treatment. Key barriers were identified from the perspectives of multiple stakeholders. Based on the findings, clinicians should encourage patients and their spouses to actively participate in decision-making, and provide objective and realistic guidance.

An appraisal of current embryo transfer strategies.

Embryo transfer, one of the most essential procedures in assisted reproductive technology, plays a vital role in the success of in-vitro fertilization and intracytoplasmic sperm injection. During the last decades, the strategies for embryo transfer have changed dramatically. In this review, we evaluate the efficacy and safety of several current embryo transfer strategies including fresh versus frozen embryo transfer, cleavage- versus blastocyst-stage embryo transfer, and single- versus double-embryo transfer. Available evidence indicates that the freeze-only strategy improves the live birth rate after the first embryo transfer in high responders while making no difference in normal responders. The risk of ovarian hyperstimulation syndrome is significantly reduced in the freeze-only strategy. Fresh blastocyst-stage embryo transfer increased live birth rate compared to cleavage-stage embryo transfer. The best embryo transfer strategy is one which tailors to individual circumstances and preferences.

Feasibility of [18F]FSPG PET for Early Response Assessment to Combined Blockade of EGFR and Glutamine Metabolism in Wild-Type KRAS Colorectal Cancer.

Early response assessment is critical for personalizing cancer therapy. Emerging therapeutic regimens with encouraging results in the wild-type (WT) KRAS colorectal cancer (CRC) setting include inhibitors of epidermal growth factor receptor (EGFR) and glutaminolysis. Towards predicting clinical outcome, this preclinical study evaluated non-invasive positron emission tomography (PET) with (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) in treatment-sensitive and treatment-resistant WT KRAS CRC patient-derived xenografts (PDXs). Tumor-bearing mice were imaged with [18F]FSPG PET before and one week following the initiation of treatment with either EGFR-targeted monoclonal antibody (mAb) therapy, glutaminase inhibitor therapy, or the combination. Imaging was correlated with tumor volume and histology. In PDX that responded to therapy, [18F]FSPG PET was significantly decreased from baseline at 1-week post-therapy, prior to changes in tumor volume. In contrast, [18F]FSPG PET was not decreased in non-responding PDX. These data suggest that [18F]FSPG PET may serve as an early metric of response to EGFR and glutaminase inhibition in the WT KRAS CRC setting.

Who can help me? Understanding the antecedent and consequence of medical information seeking behavior in the era of bigdata.

Introduction: The advent of bigdata era fundamentally transformed the nature of medical information seeking and the traditional binary medical relationship. Weaving stress coping theory and information processing theory, we developed an integrative perspective on information seeking behavior and explored the antecedent and consequence of such behavior. Methods: Data were collected from 573 women suffering from infertility who was seeking assisted reproductive technology treatment in China. We used AMOS 22.0 and the PROCESS macro in SPSS 25.0 software to test our model. Results: Our findings demonstrated that patients' satisfaction with information received from the physicians negatively predicted their behavior involvement in information seeking, such behavior positively related to their perceived information overload, and the latter negatively related to patient-physician relationship quality. Further findings showed that medical information seeking behavior and perceived information overload would serially mediate the impacts of satisfaction with information received from physicians on patient-physician relationship quality. Discussion: This study extends knowledge of information seeking behavior by proposing an integrative model and expands the application of stress coping theory and information processing theory. Additionally, it provides valuable implications for patients, physicians and public health information service providers.

Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels.

The objective of this study was to target drug delivery to radiation-induced neoantigens, which include activated receptors within the tumor vasculature. These responses include posttranslational changes in pre-existing proteins, which can be discovered by phage-displayed peptide libraries administered to mice bearing irradiated tumors. Phage-displayed peptides recovered from irradiated tumors included the amino acid sequence RGDGSSV. This peptide binds to integrins within the tumor microvasculature. Immunohistochemical staining of irradiated tumors showed accumulation of fibrinogen receptor alpha(2b)beta(3) integrin. We studied tumor targeting efficiency of ligands to radiation-induced alpha(2b)beta(3). Radiopharmaceuticals were localized to irradiated tumors by use of alpha(2b)beta(3) ligands conjugated to nanoparticles and liposomes. Fibrinogen-conjugated nanoparticles bind to the radiation-activated receptor, obliterate tumor blood flow, and significantly increase regression and growth delay in irradiated tumors. Radiation-guided drug delivery to tumor blood vessels is a novel paradigm for targeted drug delivery.

Emergency medical service utilization among acute ischemic stroke patients in Beijing: An observational study.

Objective: To investigate emergency medical service (EMS) utilization and its associated factors in patients with acute ischemic stroke (AIS), and further explore the urban-rural differences. Methods: Medical records for AIS in all emergency departments in Beijing were obtained from the Beijing Emergency Care Database from January 2018 to December 2021. EMS utilization was described and factors associated with EMS use were examined by multivariable logistic regression models with the generalized estimating equations. Results were compared between urban and rural districts. Results: A total of 24,296 AIS patients were included in the analysis, and 11,190 (46.1%) were transported to hospitals by EMS. The percentage of EMS usage in urban areas was significantly higher than that in rural areas (53.6 vs. 34.4%, P < 0.001). From 2018 to 2021, EMS utilization was on the increase (P-value for trend <0.001) with a higher average annual growth rate in rural areas (12.6%) than in urban (6.4%). Factors associated with EMS utilization were age (OR: 1.20 per 10-year increase, 95% CI: 1.17-1.23), NIHSS scores, off-hour arrival (OR: 1.32, 95% CI: 1.23-1.37), treatment in tertiary hospitals (OR: 1.75, 95% CI: 1.60-1.92), and possessing comorbidities such as coronary artery disease (OR: 1.15, 95% CI: 1.17-1.24), atrial fibrillation (OR: 1.56, 95% CI: 1.41-1.73), prior stroke (OR: 0.84, 95% CI: 0.78-0.90) or dyslipidemia (OR: 0.78, 95% CI: 0.71-0.85). Conclusion: This study demonstrated an inadequate use of EMS among AIS patients in Beijing, especially in rural areas, and revealed several associated factors. Enhanced education programs and EMS accessibility are necessary particularly for high-risk individuals and regions.

Diagnostic Accuracy of Xpert Xpress Flu/RSV for the Detection of Influenza and Respiratory Syncytial Viruses.

Xpert Xpress Flu/RSV is a fast and automated real-time nucleic acid amplification tool for detecting influenza virus and respiratory syncytial virus (RSV). The aim of this study was to verify the accuracy of Xpert Xpress Flu/RSV for detecting influenza virus and RSV. PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched up to October 2020. The quality of the original research was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 guidelines. Meta-DiSc 1.4 software was used to analyze the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic curve. Deek's funnel plot asymmetry test was used to evaluate the publication bias using the Stata 12.0 software. Ten studies with 25 fourfold tables were included in the analysis. The sensitivity of Xpert Xpress Flu/RSV for detecting influenza A, influenza B, and RSV were 0.97, 0.98, and 0.96, respectively, and the specificities were 0.97, 1.00, and 1.00, respectively. Compared with other common clinical real-time reverse transcription-polymerase chain reaction (RT-PCR), Xpert Xpress Flu/RSV is a valuable tool for diagnosing influenza virus and RSV with high sensitivity and specificity.

The fasciclin-like arabinogalactan protein gene, FLA3, is involved in microspore development of Arabidopsis.

Arabinogalactan proteins are widely distributed in plant tissues and cells, and may function in the growth and development of higher plants. To our knowledge, there is currently no direct evidence concerning the involvement of fasciclin-like arabinogalactan proteins (FLA) in sexual reproduction in Arabidopsis. In this study, Arabidopsis FLA3 was found to be specifically expressed in pollen grains and tubes. Subcellular localization showed that FLA3 anchors tightly to the plasma membrane, and its glycosylphosphatidylinositol anchor may affect its localization. FLA3-RNA interference transgenic plants had approximately 50% abnormal pollen grains (including shrunken and wrinkled phenotypes) which lacked viability. Cytological observations revealed that pollen abortion occurred during the transition from uninucleate microspores to bicellular pollens, with abnormal cellulose distribution seen by calcofluor white staining. Transmission electron microscopy showed that the basic structure of the exine layer in aberrant pollen was normal, but the intine layer appeared to have some abnormalities. Taken together, these results suggest that FLA3 is involved in microspore development and may affect pollen intine formation, possibly by participating in cellulose deposition. In FLA3-overexpressing transgenic plants, defective elongation of the stamen filament and reduced female fertility led to short siliques with low seed set, which suggested that ectopic expression of FLA3 in tissues may reduce or disrupt cell growth and then result in defects throughout the plant.