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Abstract Community structure is one of the most relevant features encountered in numerous real-world applications of networked systems. Despite the tremendous effort of a large interdisciplinary community of scientists working on this subject over the past few decades to characterize, model, and analyze communities, more investigations are needed in order to better understand the impact of community structure and its dynamics on networked systems. Here, we first focus on generative models of communities in complex networks and their role in developing strong foundation for community detection algorithms. We discuss modularity and the use of modularity maximization as the basis for community detection. Then, we follow with an overview of the Stochastic Block Model and its different variants as well as inference of community structures from such models. Next, we focus on time evolving networks, where existing nodes and links can disappear, and in parallel new nodes and links may be introduced. The extraction of communities under such circumstances poses an interesting and non-trivial problem that has gained considerable interest over the last decade. We briefly discuss considerable advances made in this field recently. Finally, we focus on immunization strategies essential for targeting the influential spreaders of epidemics in modular networks. Their main goal is to select and immunize a small proportion of individuals from the whole network to control the diffusion process. Various strategies have emerged over the years suggesting different ways to immunize nodes in networks with overlapping and non-overlapping community structure. We first discuss stochastic strategies that require little or no information about the network topology at the expense of their performance. Then, we introduce deterministic strategies that have proven to be very efficient in controlling the epidemic outbreaks, but require complete knowledge of the network.

Background: Chronic heart failure (CHF) is a major public health problem with high mortality and morbidity worldwide. Shexiang Tongxin Dropping Pill (STDP) is a widely used traditional Chinese medicine preparation for coronary heart disease and growing evidence proves that STDP exerts beneficial effects on CHF in the clinic. However, the molecular mechanism of the therapeutic effects of STDP on CHF remains largely unknown.Objective: This study aimed to elucidate the mechanism of action of STDP against CHF by integrating network pharmacology analysis and whole-transcriptome sequencing.Methods: First, the mouse model of CHF was established by the transverse aortic constriction (TAC) surgery, and the efficacy of STDP against CHF was evaluated by assessing the alterations in cardiac function, myocardial fibrosis, and cardiomyocyte hypertrophy with echocardiography, Masson’s trichrome staining, and wheat germ agglutinin staining. Next, a CHF disease network was constructed by integrating cardiovascular disease-related genes and the transcriptome sequencing data, which was used to explore the underlying mechanism of action of STDP. Then, the key targets involved in the effects of STDP on CHF were determined by network analysis algorithms, and pathway enrichment analysis was performed to these key genes. Finally, important targets in critical pathway were verified in vivo.Results: STDP administration obviously improved cardiac function, relieved cardiomyocyte hypertrophy, and ameliorated myocardial fibrosis in CHF mice. Moreover, STDP significantly reversed the imbalanced genes that belong to the disease network of CHF in mice with TAC, and the number of genes with the reverse effect was 395. Pathway analysis of the crucial genes with recovery efficiency revealed that pathways related to fibrosis and energy metabolism were highly enriched, while TGF-β pathway and ERK/MAPK pathway were predicted to be significantly affected. Consistently, validation experiments confirmed that inhibiting ERK/MAPK and TGF-β signaling pathways via reduction of the phosphorylation level of Smad3 and ERK1/2 is the important mechanism of STDP against CHF.Conclusion: Our data demonstrated that STDP can recover the imbalanced CHF network disturbed by the modeling of TAC through the multi-target and multi-pathway manner in mice, and the mechanisms are mainly related to inhibition of ERK/MAPK and TGF-β signaling pathways.

In order to determine the effect of internal cracks on the tensile failure of materials, a hybrid finite–discrete element method was used to analyze the Brazilian disc test with cracks of different angles. When the pre-crack angle is between 0° and 60°, the wing crack is initiated from the pre-crack end. When the pre-crack is 90°, the crack initiated from the pre-crack center. When the pre-crack angle is between 0° and 60°, the maximum principal stress and plastic strain are concentrated at the pre-crack end. When the pre-crack angle is 90°, the maximum principal stress and plastic strain are concentrated in the pre-crack center. As the crack angle increased from 0° to 90°, the failure mode of Brazilian discs with cracks transits from splitting into two parts to splitting into four parts. The influence of crack length is further studied. When the crack length is less than 5 mm, the crack angle has little influence on the disc failure mode; Brazilian discs with cracks of different angles undergoes splitting failure along the loading axis. When the crack length is larger than 5 mm, the crack angle has a great effect on the disc failure mode.

Background: This study aimed to explore the correlation between body mass index (BMI) and dyslipidemia and the optimal cut-off point for BMI to distinguish the risk of dyslipidemia in lactating women. Methods: A total of 2295 lactating women subjects were included in this study, all within 2 years postpartum. All samples were from “China Children and Lactating Mothers Nutritional Health Surveillance (2016–2017)”. BMI, blood lipids, demographic information, lifestyle habits, and other serum indicators were obtained in this survey. Generalized linear model, logistic regression, restricted cubic spline (RCS) and ROC curve analysis were used to evaluate the relationship among BMI, blood lipids, and dyslipidemia. Results: BMI in lactating women was positively correlated with total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), but negatively correlated with high-density lipoproteincholesterol (HDL-C) (p < 0.05). Higher BMI in lactating women was associated with higher ORs of dyslipidemia (hypercholesterolemia, hypertriglyceridemia, high-LDL-cholesterolemia, low HDL-cholesterolemia) (p < 0.05). These associations were stable across age groups, breastfeeding child age (months), parity, physical activity level, fasting plasma glucose (FPG), and hemoglobin. These factors did not interact with this relationship (p > 0.05). The optimal cut-off point for BMI was 24.85 kg/m2 determined by using ROC analysis, which can distinguish the risk of dyslipidemia. Conclusions: BMI was positively correlated with risk of dyslipidemia. Maintaining an ideal weight may prevent dyslipidemia in lactating women, and BMI is recommended to be controlled below 24.85 kg/m2.

Background: No study has explored the modification effect of ideal cardiovascular health metrics (ICVHMs) on the association between famine exposure and risk of cardiovascular disease (CVD) so far. We aim to examine the effect of ICVHMs on the association between exposure to famine early in life and the risk of CVD in adulthood.Methods: A total of 61,527 participants free of CVD were included in this study from the Kailuan Study. All participants were divided into three groups, included nonexposed, fetal-exposed, and childhood-exposed groups. Cox regression was used to estimate the effect of famine exposure and ICVHMs on CVD risk.Results: After a median of 13.0 (12.7–13.2) years follow-up, 4,814 incident CVD cases were identified. Compared with nonexposed participants, the CVD risk increased in participants with fetal famine exposure (hazard ratio [HR]: 1.21; 95% CI: 1.07–1.37), but not in childhood famine-exposed participants. After stratifying by the number of ICVHMs, the increased CVD risk associated with fetal famine exposure was only observed in participants with less ICVHMs ( ≤ 2) (HR: 1.30; 95% CI: 1.11–1.52, P for interaction=0.008), but disappeared in those with three or more ICVHMs. The modified effect of ICVHMs was sex specific (P for sex interaction = 0.031).Conclusions: Exposing to famine in the fetal period could increase the risk of CVD in late life; however, ICVHMs might modify the effect of famine exposure on CVD risk, especially in men.

Mutations in human DOCK8 cause a combined immunodeficiency syndrome characterized by allergic diseases such as asthma and food allergy. However, the underlying mechanism is unclear. Regulatory B (Breg) cells that produce IL-10 exert potent immunosuppressive functions in patients with allergic and autoimmune disorders. DOCK8-deficient B cells show diminished responses to TLR9 signaling, suggesting a possible defect in IL-10-producing Breg cells in those with DOCK8 deficiency, which may contribute to allergies. Here, we isolated peripheral blood mononuclear cells from DOCK8-deficient patients and generated a Dock8 KO mouse model to study the effect of DOCK8 deficiency on Breg cells. DOCK8-deficient patients and Dock8 KO mice harbored quantitative and qualitative defects in IL-10-producing Breg cells; these defects were caused by abnormal Dock8-/- CD4+ T cells. We found that recombinant murine (rm)IL-21 restored the function of Bregs both in vitro and in Dock8 KO mice, leading to reduced inflammatory cell infiltration of the lungs in a murine asthma model. Overall, the results provide new insight into the potential design of Breg-based or IL-21-based therapeutic strategies for allergic diseases, including asthma associated with DOCK8 deficiency.

Atopic dermatitis (AD) in early childhood is often the initial manifestation of allergic disease associated with high IgE. Accumulating evidences show that follicular helper T (Tfh) cells play a critical role in promoting B cell differentiation and IgE production, human regulatory B (Breg) cells participate in immunomodulatory processes and inhibition of allergic inflammation. However, the roles and interactions between IL-10-producing Breg cells and Tfh cells in childhood AD are unclear. In this study, we found that the percentage of CD19+IL-10+ Breg cells in children with extrinsic AD was significantly lower than that in age-matched healthy controls, and that it correlated negatively with enhanced CD4+CXCR5+PD-1+ICOS+ circulating Tfh cell responses and increased disease activity; however, there was no significant correlation with serum total IgE levels. A co-culture system revealed that Breg cells from patients with extrinsic AD cannot effectively inhibit differentiation of Tfh cells in an IL-10 dependent manner. Abnormal pSTAT3 signaling induced via Toll-like receptors (TLR), but not the B-cell receptor (BCR) signaling, might contribute to the defect of Breg cells in AD. Taken together, these observations demonstrate an important role for IL-10-producing Breg cells in inhibiting Tfh cell differentiation, and suggest that they may participate in the pathogenesis of AD.

The number of four-seed pods is one of the most important agronomic traits affected by gene and environment that can potentially improve soybean (Glycine max) yield. However, the gene regulatory network that affects the ratio of four-seed pod (the ratio of the number of four-seed pods to the total number of pods in each individual plant) is yet unclear. Here, we performed bulked segregant RNA sequencing (BSR-seq) on a series of recombinant inbred lines (RILs) derived from hybrid progenies between Heinong 48 (HN48), a cultivar with a high ratio of four-seed pod, and Henong 64 (HN64), a cultivar with a low ratio of four-seed pod. Two tissues, flower bud and young pod, at two different growth stages, R1 and R3, were analyzed under the ratios of four-seed pod at less than 10% and greater than 30%, respectively. To identify the potential gene regulation pathways associated with the ratio of soybean four-seed pod, we performed differentially expressed analysis on the four bulked groups. A differentially expressed gene (DEG) encoding a photosystem II 5-kDa protein had the function of participating in the energy conversion of photosynthesis. In addition, 79 common DEGs were identified at different developmental stages and under different ratios of four-seed pod. Among them, four genes encoding calcium-binding proteins and a WRKY transcription factor were enriched in the plant–pathogen interaction pathway, and they showed a high level of expression in roots. Moreover, 10 DEGs were identified in the reported quantitative trait locus (QTL) interval of four-seed pod, and two of them were significantly enriched in the pentose and glucuronate interconversion pathway. These findings provide basic insights into the understanding of the underlying gene regulatory network affected by specific environment and lay the foundation for identifying the targets that affect the ratio of four-seed pod in soybean.

Abstract Barcoding technology has greatly improved the throughput of cells and genes detected in single‐cell RNA sequencing (scRNA‐seq) studies. Recently, increasing studies have paid more attention to the use of this technology to increase the throughput of samples, as it has greatly reduced the processing time, technical batch effects, and library preparation costs, and lowered the per‐sample cost. In this review, the various DNA‐based barcoding methods for sample multiplexing are focused on, specifically, on the four major barcoding strategies. A detailed comparison of the barcoding methods is also presented, focusing on aspects such as sample/cell throughput and gene detection, and guidelines for choosing the most appropriate barcoding technique according to the personalized requirements are developed. Finally, the critical applications of sample multiplexing and technical challenges in combinatorial labeling, barcoding in vivo, and multimodal tagging at the spatially resolved resolution, as well as, the future prospects of multiplexed scRNA‐seq, for example, prioritizing and predicting the severity of coronavirus disease 2019 (COVID‐19) in patients of different gender and age are highlighted.

Organic dyes are widely used in the textile, biological, medical and other fields. However, a serious environmental problem has appeared because of the presence of organic dyes in industrial aqueous effluents. Thus, the efficient treatment of organic dyes in industrial wastewaters is currently in real demand. The current study investigated the oxidative degradation of the organic dye gentian violet by meso-tetra(carboxyphenyl) porphyriniron(III), [FeIII(TCPP)] as a cytochrome P450 model and iodosylbenzene (PhIO) as an oxidant at room temperature. The degradation reaction was monitored by UV–vis absorption spectroscopy via the observation of UV–vis spectral changes of the gentian violet. The results showed that the efficiency of catalyzed degradation reached more than 90% in 1 h, indicating the remarkable oxidative degradation capacity of the [FeIII(TCPP)]/PhIO system, which provided an efficient approach for the treatment of dyeing wastewater.

Heinong 84 is one of the major soybean varieties growing in Northeast China, and is resistant to the infection of all strains of soybean mosaic virus (SMV) in the region including the most prevalent strain, N3. However, the resistance gene(s) in Heinong 84 and the resistant mechanism are still elusive. In this study, genetic and next-generation sequencing (NGS)-based bulk segregation analysis (BSA) were performed to map the resistance gene using a segregation population from the cross of Heinong 84 and a susceptible cultivar to strain N3, Zhonghuang 13. Results show that the resistance of Heinong 84 is controlled by a dominant gene on chromosome 13. Further analyses suggest that the resistance gene in Heinong 84 is probably an allele of Rsv1. Finally, two pairs of single-nucleotide-polymorphism (SNP)-based primers that are tightly cosegregated with the resistance gene were designed for rapidly identifying resistant progenies in breeding via the cleaved amplified polymorphic sequence (CAPS) assay.

In this study, we investigated unmanned aerial vehicle (UAV) pollination of ‘Kuerle Xiangli’, and screened the pollination operation parameters to determine the precise parameters needed for the implementation of a ‘Kuerle Xiangli’ UAV pollination operation. Different flight height gradients, nozzle atomization particle sizes, spraying volume, and flight routes were tested and their effects on the droplets deposited were compared. UAV operation parameters were screened and field operations were conducted, comparing the fruit set rate, cost, and efficiency of different pollination methods of ‘Kuerle Xiangli’. The results show that the mist droplet effect of 1 m above the top of the tree is higher compared with that of 2 m and 3 m. The mist droplet effect of 2 L/667 m2 is better compared with that of 1.5 L/667 m2 and 1 L/667 m2. The mist droplet effect of 120 μm nozzle atomization particle size is better than that of 110 μm, 135 μm, and 150 μm. The mist droplet effect of flying above the canopy is better than that of flying between the rows of the canopy. The inflorescence and flower fruiting rates of ‘Kuerle Xiangli’ are 63.27% and 28.84%, respectively, and the inflorescence fruiting rate is not significantly different from hand and liquid sprayer pollination. The UAV pollination saves 12.69 USD/667 m2 and 3.32 USD/667 m2 compared with hand and liquid spray pollination, respectively. The efficiency of UAV pollination is greater than that of liquid and hand pollination. The best combination of parameters for pollination using a quadrotor UAV is 1 m from the top of the tree, 2 L/667 m2 spray volume, 120 μm spray nozzle particle size, and the flight path above the canopy. The cost of UAV pollination is 11.83 USD/667 m2 and the pollination efficiency 2.67 hm2/unit·h.

Soybeans are essential crops that supply protein and oil. The composition and contents of soybean fatty acids are relevant to human health and have a significant relationship with soybean oil processing and applications. Identifying quantitative trait locus (QTL) genes related to palmitic acid could facilitate the development of a range of nutritive soybean cultivars using molecular marker-assisted selection. In this study, we used a cultivar with higher palmitic acid content, ‘Dongnong42’, and a lower palmitic acid content cultivar, ‘Hobbit’, to establish F2:6 recombinant inbred lines. A high-density genetic map containing 9980 SLAF markers was constructed and distributed across 20 soybean chromosomes. The genetic map contained a total genetic distance of 2602.58 cM and an average genetic distance of 0.39 cM between adjacent markers. Two QTLs related to palmitic acid content were mapped using inclusive composite interval mapping, explaining 4.2–10.1% of the phenotypic variance in three different years and environments, including the QTL included in seed palmitic 7-3, which was validated by developing SSR markers. Based on the SNP/Indel and significant differential expression analyses of Dongnong42 and Hobbit, two genes, Glyma.15g119700 and Glyma.15g119800, were selected as candidate genes. The high-density genetic map, QTLs, and molecular markers will be helpful for the map-based cloning of palmitic acid content genes. These could be used to accelerate breeding for high nutritive value cultivars via molecular marker-assisted breeding.

Clamping effects in ferroelestastic thin films limits their usefulness for applications such as sensitive mechanical sensors. Here, the authors report on non-local mechanical force induced switching in PbTiO3 thin films by tuning the material to a state of nearly energetically degenerate co-existing domains.

Abstract Background Increasing evidence demonstrate that cadmium (Cd) has adverse effects on the mammalian reproductive system. However, the mechanisms underlying the effects of Cd on ovarian function and the strategies to reverse these effects have not been fully elucidated. Methods In this study, 60 CD-1 mice were divided into four groups (control, melatonin, Cd, Cd with melatonin). During the treatment for 14 days, body weight was measured every 2 days. After the treatment, ovaries were isolated and weighted to observe the morphological and biological characteristics. Statistical analyses were performed using one-way ANOVA followed by Fisher’s-multiple range test or chi-squared test, A P value

Abstract Background Timely and complete vaccination with multi-dose schedules is of public health importance, because an incomplete vaccination series may yield suboptimal disease protection. However, data on adherence of adults to multi-dose vaccines are limited. We sought to estimate adherence to multi-dose hepatitis vaccination schedules among adults in the United Kingdom (UK). Methods This retrospective cohort study was conducted using anonymized electronic health record (EHR) data from the Clinical Practice Research Datalink (CPRD). Individuals aged 19 years and older at their first identified dose of hepatitis vaccine (2009–2016) were included if they had continuous EHR data for 12 months before the first identified hepatitis A dose or for 6 months before the first identified hepatitis B or combination hepatitis A/B dose. We estimated dose and series completion for each vaccine and adherence to recommended vaccination schedules, as well as adherence within additional prespecified time periods after the first vaccine dose, with sensitivity analyses restricted to adults who had available data for up to 24 months after the first dose. Median time to series completion was estimated using Kaplan-Meier methods. Results Mean (SD) age at initiation was 42 (16) years for hepatitis A (n = 374,881), 40 (16) years for hepatitis B (n = 71,634), and 38 (15) years for hepatitis A/B (n = 10,335). Women comprised 52 to 55% of each vaccine cohort. Overall, 42,294 adults (11%) completed the two-dose hepatitis A vaccine series within the recommended 12 months; and 15,564 (22%) and 1076 (10%) completed the three-dose hepatitis B and hepatitis A/B series, respectively, within the recommended 6 months. These percentages rose to only 23, 35, and 33%, respectively, when the follow-up periods were extended to 36 months for hepatitis A and to 30 months for hepatitis B and A/B vaccines. Median times to series completion within recommended schedules were not reached in any cohort. Sensitivity analyses supported the primary findings for the full cohorts. Conclusions Adherence and series completion rates for hepatitis A and B vaccines in the UK are low. Identifying, understanding, and addressing barriers to series completion for multi-dose vaccines for adults in real-world settings are needed.

Middle East respiratory syndrome coronavirus (MERS-CoV) shedding and antibody responses are not fully understood, particularly in relation to underlying medical conditions, clinical manifestations, and mortality. We enrolled MERS-CoV–positive patients at a hospital in Saudi Arabia and periodically collected specimens from multiple sites for real-time reverse transcription PCR and serologic testing. We conducted interviews and chart abstractions to collect clinical, epidemiologic, and laboratory information. We found that diabetes mellitus among survivors was associated with prolonged MERS-CoV RNA detection in the respiratory tract. Among case-patients who died, development of robust neutralizing serum antibody responses during the second and third week of illness was not sufficient for patient recovery or virus clearance. Fever and cough among mildly ill patients typically aligned with RNA detection in the upper respiratory tract; RNA levels peaked during the first week of illness. These findings should be considered in the development of infection control policies, vaccines, and antibody therapeutics.

Band selection is an important preprocessing technique for hyperspectral images to select a band subset with representative information and low correlation. However, most methods focus on removing redundant components without loss of original information, but not distinguishing the noisy and low-discriminating bands which must be manually removed in advance. To find high-discriminating and high-quality bands from the original hyperspectral cube, we propose an importance-assisted column subset band selection (iCSBS) method. First, an active gradient-reference (AGR) index based on iterative reference gradient map is designed to evaluate the importance of each band. Then, the AGR index is incorporated into a column subset selection method to select high-discriminating bands, via simultaneously minimizing the redundancy and maximizing the quality of the selected band subset. Furthermore, as the high dimensionality decreases the contrast between bands, we use Manhattan distance instead of Euclidean distance. The experimental results on three real-world hyperspectral images demonstrate that the proposed method can achieve higher classification accuracy than other state-of-the-art comparison methods, and is especially superior to the geometry-based methods.

Change detection (CD) is in demand in satellite imagery processing. Inspired by the recent success of the combined transformer-CNN (convolutional neural network) model, TransCNN, originally designed for image recognition, in this paper, we present STDecoder-CD for change detection applications, which is a combination of the Siamese network (“S”), the TransCNN backbone (“T”), and three types of decoders (“Decoder”). The Type I model uses a UNet-like decoder, and the Type II decoder is defined by a combination of three modules: the difference detector, FPN (feature pyramid network), and FCN (fully convolutional network). The Type III model updates the change feature map by introducing a transformer decoder. The effectiveness and advantages of the proposed methods over the state-of-the-art alternatives were demonstrated on several CD datasets, and experimental results indicate that: (1) STDecoder-CD has excellent generalization ability and has strong robustness to pseudo-changes and noise. (2) An end-to-end CD network architecture cannot be completely free from the influence of the decoding strategy. In our case, the Type I decoder often obtained finer details than Types II and III due to its multi-scale design. (3) Using the ablation or replacing strategy to modify the three proposed decoder architectures had a limited impact on the CD performance of STDecoder-CD. To the best of our knowledge, we are the first to investigate the effect of different decoding strategies on CD tasks.

Aryl- and heteroaryl units are present in a wide variety of natural products, pharmaceuticals, and functional materials. The method for reduction of aryl halides with ubiquitous distribution is highly sought after for late-stage construction of various aromatic compounds. The visible-light-driven reduction of aryl halides to aryl radicals by electron transfer provides an efficient, simple, and environmentally friendly method for the construction of aromatic compounds. This review summarizes the recent progress in the generation of aryl radicals by visible-light-driven reduction of aryl halides with metal complexes, organic compounds, semiconductors as catalysts, and alkali-assisted reaction system. The ability and mechanism of reduction of aromatic halides in various visible light induced systems are summarized, intending to illustrate a comprehensive introduction of this research topic to the readers.

Dioxygen (O2) is an environmentally benign and abundant oxidant whose utilization is of great interest in the design of bioinspired synthetic catalytic oxidation systems to reduce energy consumption. However, it is unfortunate that utilization of O2 is a significant challenge because of the thermodynamic stability of O2 in its triplet ground state. Nevertheless, nature is able to overcome the spin state barrier using enzymes, which contain transition metals with unpaired d-electrons facilitating the activation of O2 by metal coordination. This inspires bioinorganic chemists to synthesize biomimetic small-molecule iron porphyrin complexes to carry out the O2 activation, wherein Fe-O2 species have been implicated as the key reactive intermediates. In recent years, a number of Fe-O2 intermediates have been synthesized by activating O2 at iron centers supported on porphyrin ligands. In this review, we focus on a few examples of these advances with emphasis in each case on the particular design of iron porphyrin complexes and particular reaction environments to stabilize and isolate metal-O2 intermediates in dioxygen activation, which will provide clues to elucidate structures of reactive intermediates and mechanistic insights in biological processes.

BackgroundMyopia is a complex multifactorial condition which involves several overlapping signaling pathways mediated by distinct genes. This prospective cohort study evaluated the associations of two genetic variants in the TGF-β signaling pathway with the onset and progression of myopia and ocular biometric parameters in Chinese school-aged children.MethodsA total of 556 second grade children were examined and followed up for 3.5 years. Non-cycloplegic refraction and ocular biometric parameters were measured annually. Multivariate regression analysis was used to assess the effect of the TGFBR1 rs10760673 and TGFB2-AS1 rs7550232 variants on the occurrence and progression of myopia. A 10,000 permutations test was used to correct for multiple testing. Functional annotation of single nucleotide polymorphisms (SNPs) was performed using RegulomeDB, HaploReg, and rVarBase.ResultsA total of 448 children were included in the analysis. After adjustments for gender, age, near work time and outdoor time with 10,000 permutations, the results indicated that the C allele and the AC or CC genotypes of rs7550232 adjacent to TGFB2-AS1 were associated with a significantly increased risk of the onset of myopia in two genetic models (additive: P’ = 0.022; dominant: P’ = 0.025). Additionally, the A allele and the AA or AG genotypes of rs10760673 of TGFBR1 were associated with a significant myopic shift (additive: P’ = 0.008; dominant: P’ = 0.028; recessive: P’ = 0.027). Furthermore, rs10760673 was associated with an increase in axial length (AL) (P’ = 0.013, β = 0.03) and a change in the ratio of AL to the corneal radius of curvature (AL/CRC) (P’ = 0.031, β = 0.003). Analysis using RegulomeDB, HaploReg, and rVarBase indicated that rs7550232 is likely to affect transcription factor binding, any motif, DNase footprint, and DNase peak.ConclusionThe present study indicated that rs10760673 and rs7550232 may represent susceptibility loci for the progression and onset of myopia, respectively, in school-aged children. Associations of the variants of the TGFBR1 and TGFB2-AS1 genes with myopia may be mediated by the TGF-β signaling pathway; this hypothesis requires validation in functional studies. This trial was registered as ChiCTR1900020584 at www.Chictr.org.cn.

Recent studies have shown that structuralized long non-coding RNAs (lncRNAs) play important roles in genetic and epigenetic processes. The spatial structures of most lncRNAs can be altered by distinct in vivo and in vitro cellular environments, as well as by DNA structural variations, such as single-nucleotide polymorphisms (SNPs) and variants (SNVs). In the present study, we extended candidate SNPs that had linkage disequilibria with those significantly associated with lung diseases in genome-wide association studies in order to investigate potential disease mechanisms originating from SNP structural changes of host lncRNAs. Following accurate alignments, we recognized 115 ternary-relationship pairs among 41 SNPs, 10 lncRNA transcripts, and 1 type of lung disease (adenocarcinoma of the lung). Then, we evaluated the structural heterogeneity induced by SNP alleles by developing a local-RNA-structure alignment algorithm and employing randomized strategies to determine the significance of structural variation. We identified four ternary-relationship pairs that were significantly associated with SNP-induced lncRNA allosteric effects. Moreover, these conformational changes disrupted the interactive regions and binding affinities of lncRNA-HCG23 and TF-E2F6, suggesting that these may represent regulatory mechanisms in lung diseases. Taken together, our findings support that SNP-induced changes in lncRNA conformations regulate many biological processes, providing novel insight into the role of the lncRNA “structurome” in human diseases.

Herb-induced liver injury (HILI) is a growing clinical and economic problem worldwide. However, the underlying mechanism of HILI remains largely unknown, which hinders the prevention and treatment of this disease. Recently evidence supports that microRNAs (miRNAs) in circulating exosomes and cells play an important role in the pathology of liver diseases. Thus, using Fructus Meliae Toosendan (FMT) as an example of hepatoxic herbal medicine, the aim of this study was to reveal the mechanisms of FMT-induced liver injury (FILI) through integrated analysis of serum exosomal miRNAs and liver miRNAs profiles on FMT ethyl acetate extract (FMT for short)-exposed mice. Two dosages of FMT (20 and 40 g/kg) were involved in this study, while only high-dose exposure induced obvious liver injury in mice. Pathway analysis of 209 differentially expressed miRNAs (DEMs) in serum exosomes between high-dose FMT and control groups exhibited that FILI might be regulated by apoptosis-related pathways, such as p53 signaling, PI3K/Akt signaling, and PTEN signaling. Integrated analysis of the mRNA targets of serum exosomal DEMs and liver DEMs of high-dose FMT group showed that autophagy was significantly enriched as one of the top canonical pathways in FILI. Hepatocyte apoptosis was then proved by TUNEL assay in the liver tissue of high-dose FMT-treated mice. Moreover, in vivo validation studies suggested that the protein expression levels of PTEN, p-AKT, p53, and BAX were indeed regulated in the mouse liver after high-dose FMT administration, indicating hepatocyte apoptosis may be mediated by these three pathways mentioned above. Intriguingly, PINK1/Parkin-mediated mitophagy was activated in high-dose FMT-treated mouse liver and the protective effect of autophagy in FILI was validated in vitro with an autophagic flux inhibitor. In addition, serum exosomal miR-222, the most downregulated miRNAs between low- and high-dose FMT treatments, might be an important event in the hepatocyte apoptosis by regulating PTEN and PPP2R2A. In conclusion, integrated analysis of microRNA profiles in mouse serum exosomes and liver cells provides insights into the hepatotoxicity mechanisms of FMT and discloses the protective role of autophagy in FILI, suggesting this method could contribute to deeply understand the mechanism of HILI and activation of autophagy may be a potentially therapeutic strategy for FILI even HILI.

Summary: Recent advancements in single-cell RNA sequencing (scRNA-seq) have facilitated the classification of thousands of cells through transcriptome profiling, wherein accurate cell type identification is critical for mechanistic studies. In most current analysis protocols, cell type-based cluster annotation is manually performed and heavily relies on prior knowledge, resulting in poor replicability of cell type annotation. This study aimed to introduce a single-cell Cluster-based Automatic Annotation Toolkit for Cellular Heterogeneity (scCATCH, https://github.com/ZJUFanLab/scCATCH). Using three benchmark datasets, the feasibility of evidence-based scoring and tissue-specific cellular annotation strategies were demonstrated by high concordance among cell types, and scCATCH outperformed Seurat, a popular method for marker genes identification, and cell-based annotation methods. Furthermore, scCATCH accurately annotated 67%–100% (average, 83%) clusters in six published scRNA-seq datasets originating from various tissues. The present results show that scCATCH accurately revealed cell identities with high reproducibility, thus potentially providing insights into mechanisms underlying disease pathogenesis and progression. : Quantitative Genetics; Cell Biology; Bioinformatics; Automation in Bioinformatics Subject Areas: Quantitative Genetics, Cell Biology, Bioinformatics, Automation in Bioinformatics

In recent years, the prevalence of depression has been increasing, causing a serious global burden of disease. Previous studies have proved that low-grade inflammation is involved in the process of depression. To explore the role of inflammation in the pathogenesis of senile depression, neutrophil to lymphocyte ratio (NLR) was used in this study, as a biological marker for non-specific inflammation. The present study was conducted among elderly adults from a randomly selected Community in Yangpu District, Shanghai from November 1 to December 30, 2017. 665 participants were included in the present study, including 276 males (median age was 68 years old) and 389 females (median age was 67 years old). NLR was calculated based on results of hematology examination. Depressive symptoms were assessed using the simplified version of Geriatric Depression Scale (GDS), the participant with total score greater than five points was considered to be depressed. The association between NLR and depression was evaluated separately for men and women. The prevalence of depression was 35.1% for men and 34.4% for women. No associations were found between NLR and depression among males. Nevertheless, compared with normal women, NLR was significantly increased in women with depressive symptoms (P = 0.020). Logistic regression analysis showed that NLR was independently associated with geriatric depression in women. The odds ratios (ORs) of depression was 2.152 (1.095, 4.227; P = 0.026) for the fourth compared with the first quartile of NLR. In conclusion, this study showed increased NLR was significantly associated with geriatric depression in women, but not men.

The effective conversion of carbon dioxide (CO2) into cyclic carbonates requires porous materials with high ionic content and large specific surface area. Herein, we developed a new systematic post-synthetic modification strategy for synthesizing imidazolium-based hypercrosslinked ionic polymers (HIPs) with high ionic content (up to 2.1 mmol g−1) and large specific surface area (385 m2 g−1) from porous hypercrosslinked polymers (HCPs) through addition reaction and quaternization. The obtained HIPs were efficient in CO2 capture and conversion. Under the synergistic effect of high ionic content, large specific surface area, and plentiful micro/mesoporosity, the metal-free catalyst [HCP-CH2-Im][Cl]-1 exhibited quantitative selectivities, high catalytic yields, and good substrate compatibility for the conversion of CO2 into cyclic carbonates at atmospheric pressure (0.1 MPa) in a shorter reaction time in the absence of cocatalysts, solvents, and additives. High catalytic yields (styrene oxide, 120 °C, 8 h, 94% yield; 100 °C, 20 h, 93% yield) can be achieved by appropriately extending the reaction times at low temperature, and the reaction times are shorter than other porous materials under the same conditions. This work provides a new strategy for synthesizing an efficient metal-free heterogeneous catalyst with high ionic content and a large specific surface area from HCPs for the conversion of CO2 into cyclic carbonates. It also demonstrates that the ionic content and specific surface area must be coordinated to obtain high catalytic activity for CO2 cycloaddition reaction.

For multi-temporal high resolution remote sensing images, the image registration is important but difficult due to the high resolution and low-stability land-cover. Especially, the changing of land-cover, solar altitude angle, radiation intensity, and terrain fluctuation distortion in the overlapping areas can represent different image characteristics. These time-varying properties cause traditional registration methods with known reference information to fault. Therefore, in this paper we propose a comprehensive coarse-to-fine registration (CCFR) algorithm. First, we design a low-rank constraint-based batch reference extraction (LRC-BRE) method. Under the low-rank constraint, the stable features with highly spatial co-occurrence can be reconstructed via matrix decomposition, and are set as reference images to batch registration. Second, we improve the general feature registration with block feature matching and local linear transformation (BFM-LLT) operators including match outlier filtering (MOF) on regional mutual information and dual-weighted block fitting (DWBF). Finally, based on combining LRC-BRE and BFM-LLT, CCFR is integrated. Experimental results show that the proposed method has a good batch alignment effect, especially in the registration of large difference image pairs. The proposed CCFR achieves a significant performance improvement over many state-of-the-art registration algorithms.

Abstract Background Human adenovirus (HAdV)-associated acute conjunctivitis is a common infectious disease and causes significant morbidity among residents in Beijing, China. However, little is known about the epidemiology and type distribution of acute adenoviral conjunctivitis in Beijing. Methods Acute conjunctivitis surveillance was conducted in 18 hospitals in Beijing from July through October during 2011–2013. HAdVs were detected by PCR from eye swab and types were determined by partial hexon and fiber gene sequencing. Risk factors associated with adenoviral conjunctivitis were analyzed. Results Of 876 conjunctivitis cases, 349 (39.8%) were HAdV positive. HAdV detection was most common in conjunctivitis patients aged 18–40 years; patients with contact history with a conjunctivitis case; patients with specimen collected on days 4–6 post symptom onset and patients who worked in food service as catering attendants. Fifteen types were identified among adenoviral conjunctivitis cases. Five HAdV types (HAdV-4, − 37, − 53, − 64 and − 8) accounted for 81.1% of all adenoviral conjunctivitis cases. HAdV-37, − 4 and − 53 were the most common types associated with adenoviral conjunctivitis in 2011, 2012 and 2013, respectively. Conclusion Multiple HAdV types were associated with acute conjunctivitis in Beijing. Predominant types associated with adenoviral conjunctivitis circulating in Beijing varied from year to year.

Human adenovirus type 4 (HAdV-4) is most commonly isolated in military settings. We conducted detailed molecular characterization on 36 HAdV-4 isolates recovered from civilian adults with acute respiratory disease (ARD) in the northeastern United States during 2011–2015. Specimens came from college students, residents of long-term care facilities or nursing homes, a cancer patient, and young adults without co-morbidities. HAdV-4 genome types 4a1 and 4a2, the variants most frequently detected among US military recruits in basic training before the restoration of vaccination protocols, were isolated in most cases. Two novel a-like variants were recovered from students enrolled at a college in Tompkins County, New York, USA, and a prototype-like variant distinguishable from the vaccine strain was isolated from an 18-year-old woman visiting a physician’s office in Ulster County, New York, USA, with symptoms of influenza-like illness. Our data suggest that HAdV-4 might be an underestimated causative agent of ARD among civilian adults.

Fusing panchromatic (PAN) and multispectral (MS) images, i.e., pansharpening, can obtain a high-resolution MS (HRMS) image. In this paper, we propose a spectral mapping framework for pansharpening problem based on PAN block structure analysis (PBSA). The PBSA employs boundary, inner uniqueness, and neighborhood comparisons as block structure characteristics to classify the PAN image blocks into pureness composition and mixture composition. For the PAN blocks with pureness composition, they can directly copy the spectral information of corresponding MS pixels. For the mixture PAN blocks, assuming that they can linearly represented by some pure PAN blocks, their spectral signals can get via a weighted average from the relative pure PAN blocks. The experiments on real PAN and MS pairs show that the proposed pansharpening method not only conforms to the structure of the PAN image but also preserves the spectral information of the MS image. The final fused HRMS image shows good performance in visual effect and objective assessment.

A microsphere–gel in situ forming implant (MS–Gel ISFI) dual-controlled drug delivery system was applied to a high water-soluble small-molecule compound Rasagiline mesylate (RM) for effective treatment of Parkinson’s disease. This injectable complex depot system combined an in situ phase transition gel with high drug-loading and encapsulation efficiency RM–MS prepared by a modified emulsion-phase separation method and optimized by Box–Behnken design. It was evaluated for in vitro drug release, in vivo pharmacokinetics, and in vivo pharmacodynamics. We found that the RM-MS-Gel ISFI system showed no initial burst release and had a long period of in vitro drug release (60 days). An in vivo pharmacokinetic study indicated a significant reduction (p

We characterized exposures and demographics of Middle East respiratory syndrome coronavirus cases reported to the Saudi Arabia Ministry of Health during July 1–October 31, 2017, and June 1–September 16, 2018. Molecular characterization of available specimens showed that circulating viruses during these periods continued to cluster within lineage 5.

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is an acute neurosurgical emergency with a significant fatality rate. In addition to acute brain injury, a considerable part of patients suffering from aSAH develops secondary brain damage such as cerebral vasospasm (CVS). CVS exacerbates the mortality. Therefore, it is urgently needed to find a biomarker, which could predict secondary brain and lead to operation by physicians more promptly. S100B, produced and released by astrocytes, has proven to be an important biomarker for brain injury. Methods In this present study, 51 patients with aSAH were included. Five CSF samples from each patient were obtained via lumbar puncture and were detected using electrochemiluminescence immunoassay (ECLIA). Results It indicated that S100B had a higher concentration in CSF of patients treated by surgical clipping after aSAH than that treated with endovascular coiling. In addition, the mean CSF S100B level in patients without CVS was much lower compared with patients with CVS. And, the expression of S100B increased along with the Fisher Grade at the same day after aSAH attacked and decreased as time went on. Moreover, the CSF S100B level of different time points and the mean CSF S100B level can predict the risk of CVS. Conclusions These data suggest that CSF S100B can be served as a predictor of CVS, which triggers an immediate management by clinicians to prevent secondary exacerbation.

Herpes zoster (HZ) or “shingles” results from a reactivation of the varicella zoster virus (VZV) acquired during primary infection (chickenpox) and surviving in the dorsal root ganglia. In about 20% of cases, a complication occurs, known as post-herpetic neuralgia (PHN). A live attenuated vaccine against VZV is available for the prevention of HZ and subsequent PHN. The present study aims to update an earlier evaluation estimating the cost-effectiveness of the HZ vaccine from a Swiss third party payer perspective. It takes into account updated vaccine prices, a different age cohort, latest clinical data and burden of illness data. A Markov model was developed to simulate the lifetime consequences of vaccinating 15% of the Swiss population aged 65–79 y. Information from sentinel data, official statistics and published literature were used. Endpoints assessed were number of HZ and PHN cases, quality-adjusted life years (QALYs), costs of hospitalizations, consultations and prescriptions. Based on a vaccine price of CHF 162, the vaccination strategy accrued additional costs of CHF 17,720,087 and gained 594 QALYs. The incremental cost-effectiveness ratio (ICER) was CHF 29,814 per QALY gained. Sensitivity analyses showed that the results were most sensitive to epidemiological inputs, utility values, discount rates, duration of vaccine efficacy, and vaccine price. Probabilistic sensitivity analyses indicated a more than 99% chance that the ICER was below 40,000 CHF per QALY. Findings were in line with existing cost-effectiveness analyses of HZ vaccination. This updated study supports the value of an HZ vaccination strategy targeting the Swiss population aged 65–79 y.

Among students with influenza-like illness at a Pennsylvania college student health center during 2016–2017, 44 (15%) of 288 with respiratory specimens tested positive for human adenovirus (HAdV). HAdV-3, -7, and -4 predominated, and types clustered temporally. HAdV infection should be considered among college students with acute respiratory illness.

Patients with swimming pool-acquired human adenovirus (HAdV) infections usually manifest characteristic clinical features that include fever, pharyngitis, and conjunctival inflammation, syndromically referred to as pharyngoconjunctival fever (PCF). HAdV types 3, 4, and 7 are most commonly associated with PCF. This article reports an outbreak of PCF that involved 55 students and staff at a university in Beijing, China. Fifty patients had used the same swimming pool 2 weeks before the onset of symptoms. HAdV type 4 was identified from patient eye and throat swabs and concentrated swimming pool water samples. Partial hexon gene sequences obtained from the water samples were 100% identical to the sequences obtained from the swab samples, which clustered with HAdV-4 within species E. Swimming pool water contaminated with HAdV-4 was the most likely source of infection, although one instance of likely person-to-person transmission was noted. Keywords: Pharyngoconjunctival fever, Human adenovirus, Outbreak

We describe an outbreak of severe respiratory illness associated with human coronavirus NL63 in a long-term care facility in Louisiana in November 2017. Six of 20 case-patients were hospitalized with pneumonia, and 3 of 20 died. Clinicians should consider human coronavirus NL63 for patients in similar settings with respiratory disease.

BackgroundThe United Kingdom (UK) was the first European country to introduce a national immunisation program for shingles (2013-2014). That year, vaccination coverage ranged from 50 to 64% across the UK, but uptake has declined ever since. This study explored determinants of the acceptance of the shingles vaccine in the UK.MethodsVaccinated and unvaccinated individuals, who were eligible for the last catch-up cohort of the 2014-2015 shingles vaccination campaign, were identified using the Clinical Practice Research Datalink (the National Health Service data research service) and invited to participate by their general practitioner (GP). An anonymised self-administered questionnaire was developed using the Health Belief Model as a theoretical framework, to collect data on demographic and socio-economic characteristics, health status, knowledge, influences, experiences and attitudes to shingles and the shingles vaccine. Multivariable logistic regression was used to identify the factors associated with vaccination. Physicians' views concerning perceived barriers to vaccination were also assessed.ResultsOf the 2,530 questionnaires distributed, 536 were returned (21.2%) from 69 general practices throughout the UK. The majority of responders were female (58%), lived in care homes (56%) and had completed secondary or higher education (88%). There were no differences between vaccinated and unvaccinated responders. Being offered the shingles vaccine by a GP/nurse (odds ratio (OR) = 2.3), and self-efficacy (OR = 1.2) were associated with being vaccinated (pConclusionsSocio-psychological factors largely influence shingles vaccination acceptance in this study. The results add to existing evidence that healthcare providers (HCPs) have a pivotal role against vaccine hesitancy. Campaigns focusing on GPs and accessible information offered to eligible members of the public can further enhance shingles vaccine uptake.

We evaluated the iodine nutritional status and related factors among school-age children based on the 2016 National Nutrition and Health Surveillance of Children and Lactating Women; 3808 children from Hebei, Guangxi, and Zhejiang province were included in the study. Urinary iodine concentration (UIC), thyroid-stimulating hormone (TSH), body mass index (BMI), vitamin A (VA), and vitamin D (VD) were measured. The abnormal rate of UIC and TSH were assessed. Relationships between UIC/TSH and the possible factors were analyzed. The overall median UIC was 185.14 µg/L, and the median UIC of children aged 8–10 was 164.60 µg/L. Prevalence of iodine deficiency and excess was 13.84% and 14.36%, respectively, and 12.87% of children showed TSH excess. UIC, as well as the abnormal rates of iodine deficiency (ID) and TSH, were significantly different among the three provinces. The median UICs and excess rates increased with age, reaching 211.45 µg/L and 21.35% at age of 14~, while TSH showed the opposite trend. Overweight children tended to have lower UIC and higher TSH. Higher UIC and TSH were found in VA sufficient group (p < 0.01). Further, the VD deficient group had a higher TSH compared to the sufficient group (p < 0.01). Moreover, UI and TSH distribution was obviously different among different vitamin A/D status (p < 0.05). Although the median UIC of school-age children was optimal, there were pockets of inadequate and excessive UI in the three provinces. Compared to the national IDD monitoring results in 2014, the iodine nutritional status of children was greatly improved. Considerations of region, age, BMI, VA, or VD are needed in the future iodine evaluation and surveillance.

Climate change and air pollution are emerging topics due to their possible enormous implications for health and social perspectives. In recent years, tropospheric ozone has been recognized as an important greenhouse gas and pollutant that is detrimental to human health, agriculture, and natural ecosystems, and has shown a trend of increasing interest. Machine-learning-based approaches have been widely applied to the estimation of tropospheric ozone concentrations, but few studies have included tropospheric ozone profiles. This study aimed to predict the Northern Hemisphere distribution of Lower-Stratosphere-to-Troposphere (LST) ozone at a pressure of 100 hPa to the near surface by employing a deep learning Long Short-Term Memory (LSTM) model. We referred to a history of all the observed parameters (meteorological data of European Centre for Medium-Range Weather Forecasts (ECMWF) Reanalysis v5 (ERA5), satellite data, and the ozone profiles of the World Ozone and Ultraviolet Data Center (WOUDC)) between 2014 and 2018 for training the predictive models. Model–measurement comparisons for the monitoring sites of WOUDC for the period 2019–2020 show that the mean correlation coefficients (R2) in the Northern Hemisphere at high latitude (NH), Northern Hemisphere at middle latitude (NM), and Northern Hemisphere at low latitude (NL) are 0.928, 0.885, and 0.590, respectively, indicating reasonable performance for the LSTM forecasting model. To improve the performance of the model, we applied the LSTM migration models to the Civil Aircraft for the Regular Investigation of the Atmosphere Based on an Instrument Container (CARIBIC) flights in the Northern Hemisphere from 2018 to 2019 and three urban agglomerations (the Sichuan Basin (SCB), North China Plain (NCP), and Yangtze River Delta region (YRD)) between 2018 and 2019. The results show that our models performed well on the CARIBIC data set, with a high R2 equal to 0.754. The daily and monthly surface ozone concentrations for 2018–2019 in the three urban agglomerations were estimated from meteorological and ancillary variables. Our results suggest that the LSTM models can accurately estimate the monthly surface ozone concentrations in the three clusters, with relatively high coefficients of 0.815–0.889, root mean square errors (RMSEs) of 7.769–8.729 ppb, and mean absolute errors (MAEs) of 6.111–6.930 ppb. The daily scale performance was not as high as the monthly scale performance, with the accuracy of R2 = 0.636~0.737, RMSE = 14.543–16.916 ppb, MAE = 11.130–12.687 ppb. In general, the trained module based on LSTM is robust and can capture the variation of the atmospheric ozone distribution. Moreover, it also contributes to our understanding of the mechanism of air pollution, especially increasing our comprehension of pollutant areas.

Existence of 150–170 serologically distinct human rhinoviruses (HRV) has hampered vaccine development for this human pathogen. Here, the authors show that a prime-boost regimen with an inactivated 50-valent HRV vaccine induces neutralizing antibody responses to diverse HRV serotypes in rhesus macaques.

Several human adenoviruses (HAdVs) can cause respiratory infections, some severe. HAdV-B7, which can cause severe respiratory disease, has not been recently reported in the United States but is reemerging in Asia. During October 2013–July 2014, Oregon health authorities identified 198 persons with respiratory symptoms and an HAdV-positive respiratory tract specimen. Among 136 (69%) hospitalized persons, 31% were admitted to the intensive care unit and 18% required mechanical ventilation; 5 patients died. Molecular typing of 109 specimens showed that most (59%) were HAdV-B7, followed by HAdVs-C1, -C2, -C5 (26%); HAdVs-B3, -B21 (15%); and HAdV-E4 (1%). Molecular analysis of 7 HAdV-B7 isolates identified the virus as genome type d, a strain previously identified only among strains circulating in Asia. Patients with HAdV-B7 were significantly more likely than those without HAdV-B7 to be adults and to have longer hospital stays. HAdV-B7 might be reemerging in the United States, and clinicians should consider HAdV in persons with severe respiratory infection.

We characterized Middle East respiratory syndrome coronaviruses from a hospital outbreak in Jordan in 2015. The viruses from Jordan were highly similar to isolates from Riyadh, Saudi Arabia, except for deletions in open reading frames 4a and 3. Transmissibility and pathogenicity of this strain remains to be determined.

Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is a novel respiratory pathogen first reported in 2012. During September 2014–January 2015, an outbreak of 38 cases of MERS was reported from 4 healthcare facilities in Taif, Saudi Arabia; 21 of the 38 case-patients died. Clinical and public health records showed that 13 patients were healthcare personnel (HCP). Fifteen patients, including 4 HCP, were associated with 1 dialysis unit. Three additional HCP in this dialysis unit had serologic evidence of MERS-CoV infection. Viral RNA was amplified from acute-phase serum specimens of 15 patients, and full spike gene-coding sequencing was obtained from 10 patients who formed a discrete cluster; sequences from specimens of 9 patients were closely related. Similar gene sequences among patients unlinked by time or location suggest unrecognized viral transmission. Circulation persisted in multiple healthcare settings over an extended period, underscoring the importance of strengthening MERS-CoV surveillance and infection-control practices.

Human metapneumovirus is an emerging pathogen that causes upper and lower respiratory illness. Nursing home outbreaks of infection with this virus can cause severe illness and lead to poor patient outcomes. We report an outbreak investigation in a nursing home during 2018 and infection control guidelines to assist in disease control.

Stem growth habit is an important agronomic trait in soybean and is subject to artificial selection. This study aimed to provide a theory for genotypic selection of stem growth habit for breeding purposes by analyzing the alleles of GmTfl1 gene in Chinese soybean varieties and establishing a database of GmTfl1 variation. Using knowledge of insertion and deletion (Indel) in the non-coding region and four single-nucleotide polymorphisms (SNPs) in the coding sequences of the GmTfl1 gene, four CAPS and one Indel markers were developed and used to test 1120 Chinese soybean varieties. We found that the dominant GmTfl1 allele was prevalent in accessions from the Northern ecoregion, whereas the recessive allele, Gmtfl1, was more common in the Southern ecoregion, and the proportions of GmTfl1 and recessive alleles were respectively 40.1% and 59.9% in the Huang-Huai ecoregion. The proportion of GmTfl1 decreased and that of Gmtfl1 increased, gradually from north to south. Allele GmTfl1-a was present in higher proportions in the Huang-Huai spring, Huang-Huai summer, and Northern spring sub-ecoregions than that in the other sub-ecoregions. GmTfl1-b was common in the Northeast spring, Northern spring and Southern summer sub-ecoregions. Gmtfl1-ta was found mainly in the Huang-Huai spring, Huang-Huai summer and Southern spring sub-ecoregions. The Gmtfl1-ab allele was distributed in all six soybean sub-ecoregions. The Gmtfl1-bb allele was distributed mainly in the Huang-Huai spring and summer and Southern spring and summer sub-ecoregions, but the Gmtfl1-tb allele was detected only in the Huang-Huai summer sub-ecoregion. The distributions of GmTfl1 and Gmtfl1 have shown no large changes in nearly 60 years of breeding, but the frequency of the recessive genotype Gmtfl1 has shown a rising trend in the last 20 years. This study provides a theoretical foundation for breeding new soybean varieties for different ecoregions.