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Host genetic architecture is a major factor in resistance to pathogens and parasites. The collection and analysis of sufficient data on both disease resistance and host genetics has, however, been a major obstacle to dissection the genetics of resistance to single or multiple pathogens. A severe challenge in the estimation of heritabilities and genetic correlations from pedigree-based studies has been the confounding effects of the common environment shared among relatives which are difficult to model in pedigree analyses, especially for health traits with low incidence rates. To circumvent this problem we used genome-wide single-nucleotide polymorphism data and implemented the Genomic-Restricted Maximum Likelihood (G-REML) method to estimate the heritabilities and genetic correlations for resistance to 23 different infectious pathogens in calves and cows in populations undergoing natural pathogen challenge. Furthermore, we conducted gene-based analysis and generalized gene-set analysis to understand the biological background of resistance to infectious diseases. The results showed relatively higher heritabilities of resistance in calves than in cows and significant pleiotropy (both positive and negative) among some calf and cow resistance traits. We also found significant pleiotropy between resistance and performance in both calves and cows. Finally, we confirmed the role of the B-lymphocyte pathway as one of the most important biological pathways associated with resistance to all pathogens. These results both illustrate the potential power of these approaches to illuminate the genetics of pathogen resistance in cattle and provide foundational information for future genomic selection aimed at improving the overall production fitness of cattle.

A ferrite-dielectric metamaterial composed of dielectric and ferrite cuboids has been investigated by experiments and simulations. By interacting with the electromagnetic wave, the Mie resonance can take place in the dielectric cuboids and the ferromagnetic precession will appear in the ferrite cuboids. The magnetic field distributions show the electric Mie resonance of the dielectric cuboids can be influenced by the ferromagnetic precession of ferrite cuboids when a certain magnetic field is applied. The effective permittivity of the metamaterial can be tuned by modifying the applied magnetic field. A good agreement between experimental and simulated results is demonstrated, which confirms that these metamaterials can be used for tunable microwave devices.

Background/purpose: Leptomeningeal enhancement (LME) on post-contrast FLAIR is described as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Here we report an assessment of the impact of MRI field strength and acquisition timing on meningeal contrast enhancement (MCE)., Methods: This was a cross-sectional, observational study of 95 participants with MS and 17 healthy controls (HC) subjects. Each participant underwent an MRI of the brain on both a 7 Tesla (7T) and 3 Tesla (3T) MRI scanner. 7T protocols included a FLAIR image before, soon after (Gd+ Early 7T FLAIR), and 23 minutes after gadolinium (Gd+ Delayed 7T FLAIR). 3T protocol included FLAIR before and 21 minutes after gadolinium (Gd+ Delayed 3T FLAIR)., Results: LME was seen in 23.3% of participants with MS on Gd+ Delayed 3T FLAIR, 47.4% on Gd+ Early 7T FLAIR (p = 0.002) and 57.9% on Gd+ Delayed 7T FLAIR (p < 0.001 and p = 0.008, respectively). The count and volume of LME, leptomeningeal and paravascular enhancement (LMPE), and paravascular and dural enhancement (PDE) were all highest for Gd+ Delayed 7T FLAIR and lowest for Gd+ Delayed 3T FLAIR. Non-significant trends were seen for higher proportion, counts, and volumes for LME and PDE in MS compared to HCs. The rate of LMPE was different between MS and HCs on Gd+ Delayed 7T FLAIR (98.9% vs 82.4%, p = 0.003). MS participants with LME on Gd+ Delayed 7T FLAIR were older (47.6 (10.6) years) than those without (42.0 (9.7), p = 0.008)., Conclusion: 7T MRI and a delay after contrast injection increased sensitivity for all forms of MCE. However, the lack of difference between groups for LME and its association with age calls into question its relevance as a biomarker of meningeal inflammation in MS., Competing Interests: Dr. Harrison has received research funding from EMD-Serono and Roche-Genentech and royalties/consulting fees from the American College of Physicians, Horizon Therapeutics, TG Therapeutics, EMD-Serono, and UpToDate Inc. Drs. Allette, Zeng, Cohen, Dahal, Choi, Zhuo and Hua are without disclosures. These relationships do not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

In civil engineering, stability analysis of slope is one of the main content of design. By using the finite element limit analysis software OptumG2, a landslide geological model is established to simulate the failure process of the landslide in Huadu District, Guangzhou City, China. The analysis focused on the deformation and failure characteristics, as well as the mechanical mechanism of landslide; the landslide mode of homogeneous soil is circular sliding. Additionally, investigating the influencing factors affecting slope stability is crucial in engineering implementation; in which the five influencing factors are considered as follow: slope height, slope gradient, soil cohesion, soil internal friction angle, and soil unit weight, respectively. A stability calculation model for a soil slope is established under 25 working conditions based on strength reduction method and orthogonal experimental design, in which the relationship between the safety factor and slope height, slope gradient, soil cohesion, soil internal friction angle, and soil unit weight is obtained. As the slope height increases from 5m to 45m, the safety factor of soil slope gradually decreases from 2.21 to 0.94; As the slope gradient increases from 20° to 60°, the safety factor of soil slope decreases approximately linearly from 1.80 to 0.95; As the cohesion of soil increases from 10kpa to 30kpa, the safety factor of soil slope increases approximately linearly from 1.04 to 1.60; As the internal friction angle of soil increases from 10° to 30°, the safety factor of soil slope increases approximately linearly from 1.00 to 1.81; As the unit weight of soil increases from 13kN/m3 to 21kN/m3, the safety factor of soil slope decreases approximately linearly from 1.50 to 1.21. The influencing factors affecting the safety factor of soil slope in descending order are slope height, slope angle, soil internal friction angle, soil cohesion, and soil unit weight. The research has reference significance for studying the stability and failure laws of soil slopes and conducting landslide control on soil slopes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sunflower is one of the four major oil crops in the world. 'Zaoaidatou' (ZADT), the main variety of oil sunflower in the northwest of China, has a short growth cycle, high yield, and high resistance to abiotic stress. However, the ability to tolerate adervesity is limited. Therefore, in this study, we used the retention line of backbone parent ZADT as material to establish its tissue culture and genetic transformation system for new variety cultivating to enhance resistance and yields by molecular breeding. The combination of 0.05 mg/L IAA and 2 mg/L KT in MS was more suitable for direct induction of adventitious buds with cotyledon nodes and the addition of 0.9 mg/L IBA to MS was for adventitious rooting. On this basis, an efficient Agrobacterium tumefaciens-mediated genetic transformation system for ZADT was developed by the screening of kanamycin and optimization of transformation conditions. The rate of positive seedlings reached 8.0%, as determined by polymerase chain reaction (PCR), under the condition of 45 mg/L kanamycin, bacterial density of OD600 0.8, infection time of 30 min, and co-cultivation of three days. These efficient regeneration and genetic transformation platforms are very useful for accelerating the molecular breeding process on sunflower., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The RESCUE BT2 trial recently showcased the efficacy of tirofiban in treating acute ischemic stroke (AIS) without large or medium-sized vessel occlusion. To further assess the value of tirofiban from the perspectives of Chinese and US healthcare system, a study was conducted to evaluate its cost-effectiveness., Methods: A hybrid model, integrating a short-term decision tree with a long-term Markov model, was developed to assess cost-effectiveness between tirofiban and aspirin for stroke patients without large or medium-sized vessel occlusion. Efficacy data for tirofiban was sourced from the RESCUE BT2 trial, while cost information was derived from published papers. Outcomes measured included respective cost, effectiveness, and incremental cost-effectiveness ratio (ICER). We conducted a one-way sensitivity analysis to assess the robustness of the results. Additionally, we performed probabilistic sensitivity analysis (PSA) through 10,000 Monte Carlo simulations to evaluate the uncertainties associated with the results., Results: The study revealed that tirofiban treatment in AIS patients without large or medium-sized vessel occlusion led to a considerable reduction of 2141 Chinese Yuan (CNY) in total cost, along with a lifetime gain of 0.14 quality-adjusted life years (QALYs). In the US settings, tirofiban also exhibited a lower cost ($197,055 versus $201,984) and higher effectiveness (4.15 QALYs versus 4.06 QALYs) compared to aspirin. One-way sensitivity analysis revealed that post-stroke care costs and stroke utility had the greatest impact on ICER fluctuation in both Chinese and US settings. However, these variations did not exceed the willingness-to-pay threshold. PSA demonstrated tirofiban's superior acceptability over aspirin in over 95% of potential scenarios., Conclusion: Tirofiban treatment for AIS without large or medium-sized vessel occlusion appeared dominant compared to aspirin in both China and the US., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recombinase enzymes are extremely efficient at integrating very large DNA fragments into target genomes. However, intrinsic sequence specificities curtail their use to DNA sequences with sufficient homology to endogenous target motifs. Extensive engineering is therefore required to broaden applicability and robustness. Here, we describe the directed evolution of novel lambda integrase variants capable of editing exogenous target sequences identified in the diatom Phaeodactylum tricornutum and the algae Nannochloropsis oceanica. These microorganisms hold great promise as conduits for green biomanufacturing and carbon sequestration. The evolved enzyme variants show >1000-fold switch in specificity towards the non-natural target sites when assayed in vitro. A single-copy target motif in the human genome with homology to the Nannochloropsis oceanica site can also be efficiently targeted using an engineered integrase, both in vitro and in human cells. The developed integrase variants represent useful additions to the DNA editing toolbox, with particular application for targeted genomic insertion of large DNA cargos., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Peter Droge is a co-founder and share holder of LambdaGen. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Siau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This paper investigates the sliding surface failure characteristics, earth pressure distribution law and stability safety factor of inverted T-type retaining wall by using the finite element limit analysis software OptumG2, the effects of width of wall heel plate, width of wall toe plate, thickness of bottom plate, soil-wall interface friction angle, soil cohesion and soil internal friction angle of filling on the failure characteristics of sliding surface, the earth pressure distribution law and stability safety factor of retaining walls are analyzed, The stability safety factor of the retaining wall showed a gradually increasing trend as the width of wall heel plate and wall toe plate increased; as the bottom plate thickness increases, the stability safety factor of the retaining wall gradually increases; as the soil-wall interface element reduction coefficient rises, that is, the internal friction angle of the soil-wall gradually increases to the soil internal friction angle, the stability safety factor of the retaining wall gradually increases; as the soil cohesion and internal friction angle increase, the stability safety factor of the retaining wall progressively increases. The safety factor of retaining wall increases by 0.45 for every 0.5m increase in the width of the wall heel plate; the safety factor of the retaining wall increases by 0.29 when the width of the wall toe plate increases by 0.5m; for every 0.5m increase in the width of wall plate thickness, the safety factor of the retaining wall is increased by 0.62; for every 0.25 increase in soil-wall interface element reduction coefficient, the safety factor of the retaining wall increases by 0.29; for every increase of 5KPa in soil cohesion, the safety factor of the retaining wall increased by 1.16; for every 5° increases in soil internal friction angle, the safety factor of retaining wall increases by 0.6. The research is significant for studying the failure laws and stability of retaining walls and providing references for retaining wall design., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To provide a theoretical basis for the prevention and treatment of atherosclerosis (AS), the current study aimed to investigate the mechanism underlying the effect of homocysteine (Hcy) on regulating the proliferation, migration and phenotypic transformation of vascular smooth muscle cells (VSMC) via sirtuin-1 (SIRT1)/signal transducer and activator of transcription 3 (STAT3) through Nedd4-like E3 ubiquitin-protein ligase WWP2 (WWP2). Here, Based on the establishment of ApoE-/- mouse models of high Hcy As and the model of Hcy stimulation of VSMC in vitro to observe the interaction between WWP2 and STAT3 and its effect on the proliferation, migration, and phenotypic transformation of Hcy-induced VSMC, which has not been previously reported. This study revealed that WWP2 could promote the proliferation, migration, and phenotype switch of Hcy-induced VSMC by up-regulating the phosphorylation of SIRT1/STAT3 signaling. Furthermore, Hcy might up-regulate WWP2 expression by inhibiting histone H3K27me3 expression through up-regulated UTX. These data suggest that WWP2 is a novel and important regulator of Hcy-induced VSMC proliferation, migration, and phenotypic transformation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swept the world and poses a serious threat to human health. In the post-pandemic-era, we must remain vigilant against the co-infection of SARS-CoV-2 and other respiratory viruses. More accurate and convenient detection methods are required for the diagnosis of SARS-CoV-2 due to its prolonged existence. In this study, the application value of a novel lyophilized-pellet-based 2019-nCoV nucleic acid diagnostic kit (PCoV-Kit) was evaluated by comparing it with a conventional liquid diagnostic kit (LCoV-Kit). We assessed the sensitivity, precision, accuracy, specificity, and amplification efficiency of PCoV-Kit and LCoV-Kit using diluted SARS-CoV-2 RNA reference materials. The results showed that both kits had high sensitivity, precision, accuracy, and specificity. A total of 2,033 oropharyngeal swab specimens collected during mass screening in Fuzhou in December 2022 were applied for the consistency analysis of the two reagents. In the detection of clinical oropharyngeal swab specimens, although the positive rate of PCoV-Kit (19.28%) was slightly lower than that of LCoV-Kit (20.86%), statistical analysis demonstrated a high degree of consistency between the test results obtained using both kit (χ2 = 1.57, P>0.05; Kappa coefficient = 0.90, 95%CI: 0.88-0.93). In conclusion, the use of lyophilized PCoV-Kit provides a non-inferior assay for the diagnosis of COVID-19., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Urolithiasis is a common urological disease with increasing incidence worldwide, and preventing its risk poses significant challenges. Here, we used Mendelian randomization (MR) framework to genetically assess the causal nature of multifaceted risk factors on urolithiasis., Methods: 17 potential risk factors associated with urolithiasis were collected from recently published observational studies, which can be categorized basically into lifestyle factors and circulating biomarkers. The instrumental variables of risk factors were selected from large-scale genome-wide association studies (N ≤ 607,291). Summary-level data on urolithiasis were obtained from UK Biobank (UKB) (3,625 cases and 459,308 noncases) and the FinnGen consortium (5,347 cases and 213,445 noncases). The univariable and multivariable MR analyses were applied to evaluate the causal, independent effect of these potential risk factors upon urolithiasis. Effects from the two consortia were combined by the meta-analysis methods., Results: Higher genetically predicted sex hormone-binding globulin (SHBG, OR, 0.708; 95% CI, 0.555 to 0.903), estradiol (OR, 0.179; 95% CI, 0.042 to 0.751), tea intake (OR, 0.550; 95% CI, 0.345 to 0.878), alcoholic drinks per week (OR, 0.992; 95% CI, 0.987 to 0.997), and some physical activity (e.g., swimming, cycling, keeping fit, and bowling, OR, 0.054; 95% CI, 0.008 to 0.363) were significantly associated with a lower risk of urolithiasis. In the Multivariate Mendelian Randomization (MVMR) analyses, the significant causal associations between estradiol, SHBG, tea intake, and alcoholic drinks per week with urolithiasis were robust even after adjusting for potential confounding variables. However, the previously observed causal association between other exercises and urolithiasis was no longer significant after adjusting for these factors., Conclusions: The univariable and multivariable MR findings highlight the independent and significant roles of estradiol, SHBG, tea intake, and alcoholic drinks per week in the development of urolithiasis, which might provide a deeper insight into urolithiasis risk factors and supply potential preventative strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The interaction of PD-L1 with PD-1 is a major immune checkpoint that limits effector T cell function against cancer cells; monoclonal antibodies that block this pathway have been approved in multiple tumor indications. As a next generation therapy, small molecule inhibitors of PD-L1 have inherent drug properties that may be advantageous for certain patient populations compared to antibody therapies. In this report we present the pharmacology of the orally-available, small molecule PD-L1 inhibitor CCX559 for cancer immunotherapy. CCX559 potently and selectively inhibited PD-L1 binding to PD-1 and CD80 in vitro, and increased activation of primary human T cells in a T cell receptor-dependent fashion. Oral administration of CCX559 demonstrated anti-tumor activity similar to an anti-human PD-L1 antibody in two murine tumor models. Treatment of cells with CCX559 induced PD-L1 dimer formation and internalization, which prevented interaction with PD-1. Cell surface PD-L1 expression recovered in MC38 tumors upon CCX559 clearance post dosing. In a cynomolgus monkey pharmacodynamic study, CCX559 increased plasma levels of soluble PD-L1. These results support the clinical development of CCX559 for solid tumors; CCX559 is currently in a Phase 1, first in patient, multicenter, open-label, dose-escalation study (ACTRN12621001342808)., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: At the time the studies were performed, the authors were all employees and shareholders of ChemoCentryx. The commercial affiliation with ChemoCentryx does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Sullivan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Silicosis is an uncurable occupational disease induced by crystalline silica. Increased prevalence of silicosis has resulted in the increased need for development of treatment options. Although macrophages respond first to silica, epithelial cells are also involved in silicosis. However, changes in protein and metabolite levels have not been reported simultaneously. We used mass spectrometry to profile changes in metabolites, proteins, and phosphorylation in silica-exposed BEAS-2B epithelial cells. Silica exposure increased TCA cycle, alanine, aspartate and glutamate metabolism, and aerobic glycolysis activity. In addition, protein levels in the endoplasmic reticulum were significantly altered, and phosphorylation of MAPK signaling proteins was increased. The results of this study increased understanding the role of epithelial cells in silicosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Superficial infantile hemangiomas (IH) are benign vascular tumors common in children characterized by bright red "strawberry" lesions on the skin. In order to optimize the treatment for this disease, there is a need to develop objective tools to assess treatment response. Since a color change in the lesion is a good indicator of treatment response, we have developed a digital imaging system to quantify the values of red, green, and blue (RGB) difference and RGB ratio between the tumor and normal tissue to take into account the variations in color between different skin types. The efficacy of the proposed system in assessing treatment response in superficial IH was evaluated in relation to established visual and biochemical tools used to grade hemangiomas. As the treatment progressed, the RGB ratio was almost 1, while the RGB difference was close to 0, which indicates a good response to treatment. There was a strong correlation between the RGB score and the other visual grading systems. However, the correlation between the RGB scoring system and the biochemical method was weak. These findings suggest that the system can be used clinically to objectively and accurately evaluate disease progression and treatment response in patients diagnosed with superficial IH., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Bone mineral density (BMD) in adolescence is a crucial determinant in osteoporosis and fragility fractures in older age. Vitamin E is the most abundant lipid-soluble antioxidant present in the blood. However, the association of vitamin E status with BMD in children and adolescents remains unclear., Methods: We first measured the association of vitamin E status (serum α- and γ tocopherol) with BMD in children and adolescents with the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression models were performed to evaluate their relationship after adjusting for a large range of covariates. Stratified analyses and interaction tests were used to explore their effects on different genders, ages, and races/ethnicities., Results: 13,606 children and adolescents from NHANES (2005-2006, 2017-2018) were included in our analysis. Compared with the lowest α-tocopherol quartile, individuals in the highest α-tocopherol quartile are likelier to be Non-Hispanic White and have a higher value of poverty income ratio (PIR). They have a lower value of serum phosphorus and lumbar spine BMD. Every 1umol/L increase in serum α- and γ- tocopherol, the lumbar spine BMD decreased by -0.0016 and -0.0068 g/cm2. Compared with the lowest quartile serum α- and γ- tocopherol concentration, individuals in the highest quartile have a -0.0223 and -0.0329 g/cm2 lower mean BMD, respectively. Interaction effects suggest that the negative effect is more prominent among female youth, individuals aged 8-13 years, non-Hispanic whites, Mexican Americans, and non-Hispanic blacks., Conclusions: Our study indicates serum α- and γ-tocopherol are negatively correlated with lumbar BMD. Age, gender, and race may have a modifying effect on this relationship. Our study has an important clinical implication. A higher vitamin E status for children and adolescents could not improve BMD, even decrease BMD. More prospective research with stronger evidence is needed to verify our findings and their underlying mechanisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Compared with children and immunocompromised patients, Adenovirus pneumonia in immunocompetent adults is less common. Evaluation of the applicability of severity score in predicting intensive care unit (ICU) admission of Adenovirus pneumonia is limited., Methods: We retrospectively reviewed 50 Adenovirus pneumonia inpatients in Xiangtan Central Hospital from 2018 to 2020. Hospitalized patients with no pneumonia or immunosuppression were excluded. Clinical characteristics and chest image at the admission of all patients were collected. Severity scores, including Pneumonia severity index (PSI), CURB-65, SMART-COP, and PaO2/FiO2 combined lymphocyte were evaluated to compare the performance of ICU admission., Results: Fifty inpatients with Adenovirus pneumonia were selected, 27 (54%) non-ICU and 23 (46%) ICU. Most patients were men (40 [80.00%]). Age median was 46.0 (IQR 31.0-56.0). Patients who required ICU care (n = 23) were more likely to report dyspnea (13[56.52%] vs 6[22.22%]; P = 0.002) and have lower transcutaneous oxygen saturation ([90% (IQR, 90-96), 95% (IQR, 93-96)]; P = 0.032). 76% (38/50) of patients had bilateral parenchymal abnormalities, including 91.30% (21/23) of ICU patients and 62.96% (17/27) of non-ICU patients. 23 Adenovirus pneumonia patients had bacterial infections, 17 had other viruses, and 5 had fungi. Coinfection with virus was more common in non-ICU patients than ICU patients (13[48.15%]VS 4[17.39%], P = 0.024), while bacteria and fungi not. SMART-COP exhibited the best ICU admission evaluation performance in Adenovirus pneumonia patients (AUC = 0.873, p < 0.001) and distributed similar in coinfections and no coinfections (p = 0.26)., Conclusions: In summary, Adenovirus pneumonia is not uncommon in immunocompetent adult patients who are susceptible to coinfection with other etiological illnesses. The initial SMART-COP score is still a reliable and valuable predictor of ICU admission in non-immunocompromised adult inpatients with adenovirus pneumonia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Innovation is an important driving force for high-quality regional economic development. In recent years, the Chinese government has actively explored new ways to improve regional innovation level, and the construction of smart cities is regarded as an important measure to implement the innovation-driven development strategy. Based on the panel data of 287 prefecture-level cities in China from 2001 to 2019, this paper examined the impact of smart city construction on regional innovation. The research shows that: (i) The construction of smart city has significantly improved the level of regional innovation; (ii) Investment in science and technology and human capital level are important transmission paths for smart city construction to affect regional innovation; (iii) Compared with the central and western regions, the impact of smart city construction on regional innovation is more obvious in the eastern region. This study deepens the understanding of smart city construction, which has important policy significance for China to accelerate the construction of an innovative country and the healthy development of smart cities, and provides reference for other developing countries to promote smart city construction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Measurement of care quality and safety mainly relies on abstracted administrative data. However, it is well studied that administrative data-based adverse event (AE) detection methods are suboptimal due to lack of clinical information. Electronic medical records (EMR) have been widely implemented and contain detailed and comprehensive information regarding all aspects of patient care, offering a valuable complement to administrative data. Harnessing the rich clinical data in EMRs offers a unique opportunity to improve detection, identify possible risk factors of AE and enhance surveillance. However, the methodological tools for detection of AEs within EMR need to be developed and validated. The objectives of this study are to develop EMR-based AE algorithms from hospital EMR data and assess AE algorithm's validity in Canadian EMR data., Methods: Patient EMR structured and text data from acute care hospitals in Calgary, Alberta, Canada will be linked with discharge abstract data (DAD) between 2010 and 2020 (n~1.5 million). AE algorithms development. First, a comprehensive list of AEs will be generated through a systematic literature review and expert recommendations. Second, these AEs will be mapped to EMR free texts using Natural Language Processing (NLP) technologies. Finally, an expert panel will assess the clinical relevance of the developed NLP algorithms. AE algorithms validation: We will test the newly developed AE algorithms on 10,000 randomly selected EMRs between 2010 to 2020 from Calgary, Alberta. Trained reviewers will review the selected 10,000 EMR charts to identify AEs that had occurred during hospitalization. Performance indicators (e.g., sensitivity, specificity, positive predictive value, negative predictive value, F1 score, etc.) of the developed AE algorithms will be assessed using chart review data as the reference standard., Discussion: The results of this project can be widely implemented in EMR based healthcare system to accurately and timely detect in-hospital AEs., Competing Interests: The authors have declared that no competing interests exist.

Objective: To identify and compare prognostic accuracy of quick Sequential Organ Failure Assessment (qSOFA) score, Systemic Inflammatory Response Syndrome (SIRS) criteria, and National Early Warning Score (NEWS) to predict mortality in patients with suspected sepsis., Methods: This meta-analysis followed accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched PubMed, EMBASE, Web of Science, and the Cochrane Library databases from establishment of the database to November 29, 2021. The pooled sensitivity and specificity with 95% CIs were calculated using a bivariate random-effects model (BRM). Hierarchical summary receiver operating characteristic (HSROC) curves were generated to assess the overall prognostic accuracy., Results: Data of 62338 patients from 26 studies were included in this meta-analysis. qSOFA had the highest specificity and the lowest sensitivity with a specificity of 0.82 (95% CI: 0.76-0.86) and a sensitivity of 0.46 (95% CI: 0.39-0.53). SIRS had the highest sensitivity and the lowest specificity with a sensitivity of 0.82 (95% CI: 0.78-0.85) and a specificity 0.24 (95% CI: 0.19-0.29). NEWS had both an intermediate sensitivity and specificity with a sensitivity of 0.73 (95% CI: 0.63-0.81) and a specificity 0.52 (95% CI: 0.39-0.65). qSOFA showed higher overall prognostic accuracy than SIRS and NEWS by comparing HSROC curves., Conclusions: Among qSOFA, SIRS and NEWS, qSOFA showed higher overall prognostic accuracy than SIRS and NEWS. However, no scoring system has both high sensitivity and specificity for predicting the accuracy of mortality in patients with suspected sepsis., Competing Interests: The authors have declared that no competing interests exist.

Determining the genetic basis of yield and water deficient tolerance in wheat is vital for wheat breeding programs. Herein, a genome-wide association study (GWAS) was performed for water deficient and yield-related attributes on wheat genotypes with high-density Illumina 90K Infinium SNP array. Major yield and drought-related attributes were phenotyped on a panel of Pakistani and foreign accessions grown in non-stressed and water deficient stressed environments during two crop cycles. Among all accessions, highly significant variations were shown in studied environments for examined characters. Water deficient conditions, reduced the wheat yield and had strong and positive correlation among relative water content and grain yield per plant. Population structure analyses based on 90,000 SNP data, classify the accessions into 4 sub-populations. Marker-trait association analyses (MTA) revealed that 134 significant SNPs were linked with yield and drought tolerance attributes. Pleotropic loci RAC875&#95;s117925&#95;244 and RAC875&#95;c16333&#95;340 located on chromosome 5A and 2A respectively, were significantly linked with relative water contents (RWC), cell membrane thermo-stability (CMT), grain per spike (GPS), spikelet per spike (SPS) and grain yield per plant (GYP). The markers Ra&#95;c58279&#95;684, BobWhite&#95;c23828&#95;341 and IAAV3414 located on chromosomes 2A, 6B and 7B respectively, showed pleotropic effects for RWC, GPS and GYP under both environments. The current experiment not only validated several MTAs reported in other studies but also discovered novel MTAs which significant under drought-stressed conditions. A total of 171 candidate genes were recognized that could be cloned and functionally characterized for the respective associated traits. For RWC and CMT, total 11 and 3 associated SNPs were mapped on coding DNA sequence (CDS) of the identified candidate genes. Isolation and characterization of the candidate genes herein mapped SNPs will be useful in discovering novel genes underpinning drought tolerance in bread wheat to fulfill the wheat demand and sustainable food security under limited water conditions., Competing Interests: No conflict of interest exits in the submission of this manuscript.

To achieve the goal of "emission peak and carbon neutrality", it is particularly important to accelerate the transformation of low-carbon production as the construction industry of China's major carbon emission. Considering the national industrial management system, this paper constructs a stochastic game model of supplier group's production strategy in construction supply chain based on Moran process, analyzes the conditions for low-carbon emission strategy to fixate in supplier populations and become an evolutionary stable strategy, then, carries out numerical analysis on fixation probability and fixation times, and the influence of various factors on the evolution process is discussed, such as the initial willingness of suppliers to choose low-carbon emission strategy, the cost subsidy coefficient of government to low carbon suppliers, the reward and punishment of government and the credibility of suppliers. The results show that on the basis of vigorously promoting environmental protection, the government should implement a differentiated treatment policy through the establishment of carbon emissions standards, cost subsidies, incentives and punishment measures, and information disclosure systems to guide supplier groups to transformation into low-carbon production., Competing Interests: The authors have declared that no competing interests exist.

Topiramate (TPM) was an antiepileptic agent commonly used in clinical. Studies showed that an oral preparation of TPM with extended-release manner could bring some benefits for epileptics. In this paper, controlled release push-pull osmotic pump (PPOP) tablets of sparingly water-soluble TPM were successfully prepared. This bi-layer tablet core mainly consisted of sodium chloride as osmotic promoting agent and polyethylene oxide as suspending and pushing agents. The influences of osmotic agents, pushing agents and the compositions of coating membrane on TPM release profiles were evaluated. An optimal formulation of TPM-PPOP was obtained through single-factor experiments. In vitro release tests showed that the optimum formulation could release TPM at an approximate zero-order rate up to 8 h. Pharmacokinetic behaviors of TPM-PPOP tablets were evaluated and compared with the immediate release capsules after an oral single dose in beagle dogs. Pharmacokinetics results demonstrated that the TPM-PPOP tablet was able to provide a prolonged release of TPM with longer tmax and mean residence time. Lower fluctuations of drug plasma levels could also be achieved with TPM-PPOP tablets. These results suggested that sparely water-soluble drugs as TPM can be designed to PPOP for efficacy and safety use., Competing Interests: The authors have declared that no competing interests exist.

Globally, anxiety and depression are the most common psychiatric disorders that add large burdens to individuals and society; however, the mechanisms underlying these disorders are unclear. Several studies have found that eczema is a shared risk factor for both these conditions. We identified and evaluated eligible observational studies from EMBASE and PubMed. In total, 20 relevant cohort and case-control studies comprising 141,910 patients with eczema and 4,736,222 control participants fulfilled our established criteria. Information extracted included study design, location, sample size, sex distribution of cases and controls or reference cohorts, measurements of outcomes, odds ratio (OR) with 95% confidence interval (CI), and adjusted factors for exposure associated with outcome risk. The meta-analysis was performed by calculating the pooled OR with 95% CI, and heterogeneity was assessed using Cochrane Q and I2 statistics. The pooled effect showed a positive association (n = 4,896,099, OR = 1.63, 95% CI [1.42-1.88], p<0.001) between eczema and depression or anxiety, with positive associations also observed in the depression (n = 4,878,746, OR = 1.64, 95% CI [1.39-1.94], p<0.001) and anxiety (n = 4,607,597, OR = 1.68, 95% CI [1.27-2.21], p<0.001) groups. Subgroup and sensitivity analyses confirmed that these findings were stable and reliable. This study suggests that eczema is associated with an increased risk of developing depression and anxiety, which may assist clinicians in the prevention or treatment of these disorders., Competing Interests: The authors have declared that no competing interests exist.

Dissecting the genetic basis of physiological and yield traits against tolerance to heat stress is an essential in wheat breeding programs to boost up the wheat yield for sustainable food security. Herein, a genome-wide association study (GWAS) was performed to reveal the genetic basis of heat tolerance using high-density Illumina 90K Infinium SNPs array through physiological and yield indices. These indices were phenotyped on a diverse panel of foreign and domestic genotypes of Pakistan, grown in normal and heat-stressed environments. Based on STRUCTURE analysis, the studied germplasm clustered into four sub-population. Highly significant variations with a range of moderate (58.3%) to high (77.8%) heritability was observed under both conditions. Strong positive correlation existed among physiological and yield related attributes. A total of 320 significant (-log10 P ≥ 3) marker-trait associations (MTAs) were identified for the observed characters. Out of them 169 and 151 MTAs were recorded in normal and heat stress environments, respectively. Among the MTA loci, three (RAC875&#95;c103017&#95;302, Tdurum&#95;contig42087&#95;1199, and Tdurum&#95;contig46877&#95;488 on chromosomes 4B, 6B, and 7B respectively), two (BobWhite&#95;c836&#95;422 and BS00010616&#95;51) and three (Kukri&#95;rep&#95;c87210&#95;361, D&#95;GA8KES401BNLTU&#95;253 and Tdurum&#95;contig1015&#95;131) on chromosomes 5A, 1B, and 3D at the positions 243.59cM, 77.82cM and 292.51cM) showed pleiotropic effects in studied traits under normal, heat-stressed and both conditions respectively. The present study not only authenticated the numerous previously reported MTAs for examined attributes but also revealed novel MTAs under heat-stressed conditions. Identified SNPs will be beneficial in determining the novel genes in wheat to develop the heat tolerant and best yielded genotypes to fulfill the wheat requirement for the growing population., Competing Interests: The authors have declared that no competing interests exist

Objectives: Among older adults in China and the US, we aimed to compare the biomarkers of chronic-kidney-diseases (CKD), factors associated with CKD, and the correlation between CKD and mortality., Setting: China and the US., Study Design: Cross-sectional and prospective cohorts., Participants: We included 2019 participants aged 65 and above from the Chinese Longitudinal Healthy Longevity Study (CLHLS) in 2012, and 2177 from US National Health and Nutrition Examination Survey (NHANES) in 2011-2014., Outcomes: Urinary albumin, urinary creatinine, albumin creatinine ratio (ACR), serum creatinine, blood urea nitrogen, plasma albumin, uric acid, and estimated glomerular filtration rate (eGFR). CKD (ACR ≥ 30 mg/g or eGFR< 60 ml/min/1.73m2) and mortality., Analytical Approach: Logistic regression and Cox proportional hazard models. Covariates included age, sex, race, education, income, marital status, health condition, smoking and drinking status, physical activity and body mass index., Results: Chinese participants had lower levels of urinary albumin, ACR, and uric acid than the US (mean: 25.0 vs 76.4 mg/L, 41.7 vs 85.0 mg/g, 292.9 vs 341.3 μmol/L). In the fully-adjusted model, CKD was associated with the risk of mortality only in the US group (hazard ratio [HR], 95% CI: 2.179, 1.561-3.041 in NHANES, 1.091, 0.940-1.266 in CLHLS). Compared to eGFR≥90, eGFR ranged 30-44 ml/min/1.73m2 was only associated with mortality in the US population (HR, 95% CI: 2.249, 1.141-4.430), but not in the Chinese population (HR, 95% CI: 1.408, 0.884-2.241)., Conclusions: The elderly participants in the US sample had worse CKD-related biomarker levels than in China sample, and the association between CKD and mortality was also stronger among the US older adults. This may be due to the biological differences, or co-morbid conditions., Competing Interests: The authors have declared that no competing interests exist.

This study aimed to examine the impact of short-term adiposity change on risk of high blood pressure (HBP), and to assess the low limit range of body mass index (BMI) and waist-to-height ratio (WHtR) reduction proposed to decrease the HBP risk in children. Children were longitudinally surveyed at baseline and after a short-term follow-up. General obesity (GOB) is categorized by age and gender-specific BMI cut-off points, abdominal obesity (AOB) by WHtR. Logistic regression model was used to estimate relations between adiposity change and HBP risk with adjustment of covariates. A total of 28,288 children (median of baseline age:10 years) were involved with follow-up of 6.88±1.20 months. After the follow-up, 9.4% of the children had persistent general obesity (GOB), 2.8% converted from GOB to non-GOB, 0.9% had newly developed GOB. When compared with children remained non-GOB, children with continuous GOB status, newly developed GOB, converting from GOB to non-GOB had 5.03-fold (95%CI: 4.32~5.86), 3.35-fold (95%CI: 1.99~5.65), 2.72-fold (2.03~3.63) HBP risk, respectively. Similar findings were observed for abdominal obesity (AOB). Reduction of 0.21-0.88 kg/m2 of baseline BMI (0.86-3.59%) or 0.009-0.024 of baseline WHtR (1.66-4.42%) in GOB or AOB children, respectively, was associated with significant decrease in HBP risk. Children with persistent obesity, newly developed obesity, or converting from obese to non-obese had significantly higher HBP risk. For children with GOB or AOB, reduction of <3.6% in BMI or <4.5% in WHtR could decrease the HBP risk., Competing Interests: The authors have declared that no competing interests exist.

Autophagy is the primary intracellular catabolic process for degrading and recycling long-lived proteins and damaged organelles, which maintains cellular homeostasis. Autophagy has key roles in development and differentiation. By using the mouse with liver specific knockout of autophagy related gene 5 (Atg5), a gene essential for autophagy, we investigated the possible role of autophagy in liver regeneration after 70% partial hepatectomy (PHx). Ablation of autophagy significantly impaired mouse liver regeneration, and this impairment was associated with reduced hepatocellular proliferation rate, down-regulated expression of cyclins and tumor suppressors, and increased hepatocellular apoptosis via the intrinsic apoptotic pathway. Ablation of autophagy does not affect IL-6 and TNF-α response after PHx, but the altered hepatic and systemic metabolic responses were observed in these mice, including reduced ATP and hepatic free fatty acid levels in the liver tissue, increased glucose level in the serum. Autophagy is required to promote hepatocellular proliferation by maintaining normal hepatic and systemic metabolism and suppress hepatocellular apoptosis in liver regeneration., Competing Interests: The authors have declared that no competing interests exist.

Sarcopenia is a progressive generalized skeletal muscle disorder, which may increase the risk of osteopenia. The aim of this study was to systematically review studies on the association between sarcopenia and osteopenia by pooled analysis. The PubMed and Embase databases were searched from inception to October 2020 for studies focusing on the association between sarcopenia and osteopenia. Two reviewers independently extracted data and assessed study quality. A pooled analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) using random-effects models. Subgroup analysis was conducted to explore the source of heterogeneity and the stability of outcome. A total of 25 independent studies involving 47,744 participants fulfilled the inclusion criteria. Sarcopenia significantly increased the risk of osteopenia (OR, 2.08; 95% CI, 1.66-2.60); Sensitivity analyses indicated the outcome was stable. Subgroup analyses showed that sarcopenia significantly increased osteopenia risk in each subgroup. No evidence of publication bias among the studies existed. In this study, our findings showed that sarcopenia significantly increased the risk of osteopenia. Thus, we suggest that sarcopenia can be a predictor of osteopenia risk., Competing Interests: The authors have declared that no competing interests exist.

On the basis of the spatial panel data of 2000, 2005, 2010, and 2015, this study uses a mixed geographically weighted regression model to explore the spatial distribution characteristics and influencing factors of the rural (permanent) population in Jiangxi Province, China. Results show that residents in the county area have a significant spatial positive autocorrelation, especially in the lake and mountain areas and the global Moran' I index is more than 0.05. The influence of social and economic factors presents spatial homogeneity. The effect of urbanization and per capita disposable income is negative, whereas that of agricultural output value and rural electricity consumption is positive. The influence of climate factors presents spatial heterogeneity. The influence coefficient of rainfall in 2015 ranges from [-0.061, 0.133], which has a negative effect on the southwest mountain areas and a positive effect on the northeast lake areas., The influence coefficient of temperature in 2015 ranges from [-0.110, 0.094], which has a positive effect on the southwest mountain areas and a negative effect on the northeast lake areas. The influence coefficients of wind speed and relative humidity range from [-0.090, 0.153] and [-0.069, 0.130] in 2015 respectively, which further reinforce this effect. Therefore, scholars should pay attention to the universal adaptability of economic and social factors. Moreover, they should consider the spatial difference of climatic factors to promote urbanization following the local conditions. Finally, policymakers and concerned non-governmental institutions should fully understand the sensitivity of the rural population in underdeveloped mountain areas to climate factors to promote their rational distribution., Competing Interests: The authors have declared that no competing interests exist.

Biological invasions have created detrimental impacts in freshwater ecosystems. As non-native freshwater species include economically beneficial, but also harmful, species, trait-based risk assessments can be used to identify and prevent the import of potentially invasive species. Freshwater fishes are one of the most evaluated freshwater taxa to date. However, such assessments have mostly been done in sub-temperate to temperate regions, with a general lack of such research in the tropics. In view of this knowledge gap, this study aims to determine if a different set of traits are associated with successful establishment of non-native fishes within the tropics. In tropical Southeast Asia, Singapore represents a suitable model site to perform an invasive species trait-based risk assessment for the tropical region given its susceptibility to the introduction and establishment of non-native freshwater fishes and lack of stringent fish import regulation. A quantitative trait-based risk assessment was performed using random forest to determine the relative importance of species attributes associated with the successful establishment of introduced freshwater fishes in Singapore. Species having a match in climate, prior invasion success, lower absolute fecundity, higher trophic level, and involvement in the aquarium trade were found to have higher establishment likelihood (as opposed to native distributional range and maximum size being among the commonly identified predictors in subtropical/temperate trait-based risk assessments). To minimize invasive risk, incoming freshwater fishes could be screened in future for such traits, allowing lists of prohibited or regulated species to be updated. The findings could also potentially benefit the development of invasive species action plans and inform management decisions in the Southeast Asian region. Considering a geographical bias in terms of having relatively less documentation of biological invasions in the tropics, particularly Asia, this study highlights the need to perform more of such risk assessments in other parts of the tropics., Competing Interests: The authors have declared that no competing interests exist.

Many countries have been implementing various control measures with different strictness levels to prevent the coronavirus disease 2019 (COVID-19) from spreading. With the great reduction in human mobility and daily activities, considerable impacts have been imposed on the global air transportation industry. This study applies a hybrid SARIMA-based intervention model to measure the differences in the impacts of different control measures implemented in China, the U.S. and Singapore on air passenger and air freight traffic. To explore the effect of time span for the measures to be in force, two scenarios are invented, namely a long-term intervention and a short-term intervention, and predictions are made till the end of 2020 for all three countries under both scenarios. As a result, predictive patterns of the selected metrics for the three countries are rather different. China is predicted to have the mildest economic impact on the air transportation industry in this year in terms of air passenger revenue and air cargo traffic, provided that the control measures were prompt and effective. The U.S. would suffer from a far-reaching impact on the industry if the same control measures are maintained. More uncertainties are found for Singapore, as it is strongly associated with international travel demands. Suggestions are made for the three countries and the rest of the world on how to seek a balance between the strictness of control measures and the potential long-term industrial losses., Competing Interests: The authors have declared that no competing interests exist.

The research on rural population distribution from a climate perspective is rare. Therefore, this study adopts this perspective and uses the ordinary least squares and spatial econometric models to explore the spatial distribution characteristics of the rural population in the Poyang Lake ecological economic zone. Results show that (1) a significant spatial autocorrelation is present in the distribution of rural population, and a spatial correlation exists between the population distribution and climatic factors, (2) the influence of climatic factors on the distribution of rural population in the Poyang Lake ecological economic zone is greater than that of economic factors, and (3) the annual average sunshine and annual average rainfall have a significant negative effect on the distribution of the regional rural population, which is contrary to the expectations., so we then analyze this negative effect on the regional rural population distribution. It is found that (1) the influence of climate factors on the distribution of rural population in lake area is far more than that of economic factors, and more consideration should be given to the influence of climate factors on the population distribution in the lake area, (2) different geographical capital and natural resource endowment, the influence of climate on micro-regional population distribution may be different from the general law, (3) the spatial measurement model which takes spatial dependence into account can reveal the influence of climate on rural population distribution more accurately., Competing Interests: The authors have declared that no competing interests exist.

Nutrient addition to forest ecosystems significantly influences belowground microbial diversity, community structure, and ecosystem functioning. Nitrogen (N) addition in forests is common in China, especially in the southeast region. However, the influence of N addition on belowground soil microbial community diversity in subtropical forests remains unclear. In May 2018, we randomly selected 12 experimental plots in a Pinus taiwanensis forest within the Daiyun Mountain Nature Reserve, Fujian Province, China, and subjected them to N addition treatments for one year. We investigated the responses of the soil microbial communities and identified the major elements that influenced microbial community composition in the experimental plots. The present study included three N treatments, i.e., the control (CT), low N addition (LN, 40 kg N ha-1 yr-1), and high N addition (HN, 80 kg N ha-1 yr-1), and two depths, 0-10 cm (topsoil) and 10-20 cm (subsoil), which were all sampled in the growing season (May) of 2019. Soil microbial diversity and community composition in the topsoil and subsoil were investigated using high-throughput sequencing of bacterial 16S rDNA genes and fungal internal transcribed spacer sequences. According to our results, 1) soil dissolved organic carbon (DOC) significantly decreased after HN addition, and available nitrogen (AN) significantly declined after LN addition, 2) bacterial α-diversity in the subsoil significantly decreased with HN addition, which was affected significantly by the interaction between N addition and soil layer, and 3) soil DOC, rather than pH, was the dominant environmental factor influencing soil bacterial community composition, while AN and MBN were the best predictors of soil fungal community structure dynamics. Moreover, N addition influence both diversity and community composition of soil bacteria more than those of fungi in the subtropical forests. The results of the present study provide further evidence to support shifts in soil microbial community structure in acidic subtropical forests in response to increasing N deposition., Competing Interests: The authors have declared that no competing interests exist.

Background: Coronavirus disease 2019 (COVID-19) has spread to the world. Whether there is an association between lifestyle behaviors and the acquisition of COVID-19 remains unclear., Methods: In this case-control study, we recruited 105 patients with SARS-CoV-2 infection as a case group from the Wuhan Tongji Hospital (Wuhan, China). For each case two control subjects were recruited. Participants were randomly selected from communities in Wuhan and matched for sex, age (± 2yrs), and pre-existing comorbidities (hypertension and diabetes)., Results: A total of 105 patients diagnosed with COVID-19 and 210 controls were included. Compared with control group, the case group had higher proportions of lack of sleep (30.5% vs. 14.8%, P = 0.001) and increased physical activities (56.2% vs. 32.9%, P < 0.001). And patients in the case group were more likely to have alopecia (28.6% vs. 10.0%, P < 0.001) than people from the control group. Overall, we found that lack of sleep [adjusted odds ratio (OR) 1.56, 95% confidence interval (CI) 1.03-2.39)], physical activities (≥ 5 times a week) (adjusted OR 2.05, 95%CI 1.39-3.02) and alopecia (adjusted OR 1.73, 95%CI 1.13-2.66) were independent risk factors for COVID-19 infection. Conversely, low-dose alcohol intake (<100g alcohol per week), hand hygiene, and fruits intake (daily) were significantly associated with a decrease in morbidity., Conclusions: Individual lifestyle behaviors and health status can affect the occurrence of COVID-19., Competing Interests: The authors have declared that no competing interests exist.

Background: Depression is one of the most common mental disorders, profoundly impacting an individual's performance and quality of life. Due to their unique working conditions, nursing is counted among the occupational groups at high risk for developing depression. Because of the shortage of nursing resources in China, Chinese nurses suffer from heavy daily workloads more than those in many other countries. Therefore, this study aimed to evaluate the overall prevalence of depressive symptoms and analyse the potential risk factors of depressive symptoms in Chinese nurses., Methods: A systematic literature search in PubMed, EMBASE, Web of Science, the Chinese BioMedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI), and the Weipu and Wanfang databases up to Dec 31st, 2019 was performed regarding the prevalence of depressive symptoms in Chinese nurses. Eligibility assessment and data extraction were performed independently by 2 researchers, and meta-analysis was used to synthesize the data. Heterogeneity was evaluated using Cochran's Q test and quantified using the I2 statistic. To explore the potential source of heterogeneity, subgroup analyses were also performed. In addition, both funnel plot and Egger's tests were adopted to assess publication bias., Results: A total of 102 studies published from 1996 to 2019 covering 22 provinces were included for further analysis. The total number of participants was 52,592, with a range of 46 to 7205 per study. The overall prevalence of depressive symptoms in Chinese nurses was 43.83% (95%CI: 40.26%-47.42%), and 31.12% (95%CI: 27.30%-35.07%) were classified as mild degrees of depressive symptoms. The prevalence of depressive symptoms may be significantly affected by region, province or municipality and department marital status. Moreover, an increasing trend in the prevalence of depressive symptoms was observed in recent years., Conclusion: The results presented a high prevalence of depressive symptoms among Chinese nurses, which suggests interventional programmes by health decision-makers to improving the mental state of nurses is needed urgently, especially in nurses with high risk factors for depressive symptoms. Furthermore, the nationwide investigation of depressive symptoms prevalence should be performed with a standard diagnostic tool, which may be more useful for policy makers and planners., Competing Interests: No authors have competing interests.

To explore the molecular mechanism of the effect of Bacillus cereus PAS38 on the immunity of broilers, sixty 7-day-old broilers were divided into two groups with three replicates. The control group was fed with basal diet, and the treatment group was fed with basal diet containing Bacillus cereus PAS38 1×106 CFU/g. Thymus and bursa of fabricius were taken from two groups of broilers at the age of 42 days, total RNA was extracted, differential gene library was constructed by SSH technology, and immune-related differential genes were screened. Then, we used siRNA to interfere with the expression of some differential genes in the original generation lymphocytes of broiler blood to detect the change of cytokines mRNA expression level. A total of 42 immune-related differentially expressed genes were screened, including 22 up-regulated genes and 20 down-regulated genes. When 7 differentially up-regulated genes associated with enhanced immune function were interfered with in lymphocytes, some immune-promoting cytokines were down-regulated. These results showed that Bacillus cereus PAS38 might up-regulate the expression of JCHAIN, PRDX1, CD3E, CDK6 and other genes in immune organs of broilers, thereby affecting the development of immune organs, the expression of various cytokines and the transduction of immune signals, improving the immune capacity of broilers., Competing Interests: The authors have declared that no competing interests exist.

Ecological restoration of degraded riparian Tugai forests is a key driver to combat desertification in arid regions. Previous studies have focused mainly on changes in groundwater as the underlying mechanisms of Tugai forest's decline. We evaluated species composition and diversity of Tugai forest and their relationship to groundwater, soil salinity, and soil nutrient. Using 73 quadrats (100 m × 100 m) from 13 transects located perpendicularly to river in the upper reaches of the Tarim River. Eighteen plant species belonging to sixteen genera and eight families were recorded, and the dominant species included Populus euphratica, Phragmites communis, and Tamarix ramosissima. Three P. euphratica stand ages were detected: young stand, mature stand, and old stand. There were significant differences in species diversity, groundwater depth, groundwater salinity, distance from the quadrat to the river channel, soil moisture content, pH, electrical conductivity, total salt, Cl-, SO42-, Ca2-, Mg2+, Na+, K+, soil organic carbon, and soil organic matter across the stand ages. Seven species were identified as indicators of the three stand ages. Redundancy analysis indicated that the Tugai forest diversity indices were negatively correlated with groundwater depth, groundwater salinity, and distance from the river, and positively associated with electrical conductivity, total salt, pH, Cl-, SO42-, CO32-, soil organic matter, soil organic carbon, and soil moisture content. Plant diversity was the highest at 3-6 m groundwater depth, followed by 0-3 m and then 6-9 m, with the lowest recorded at > 9 m. The appropriate groundwater depth for herbs was about 1-4 m, whereas the depth for trees and shrubs was about 3-6 m. The groundwater depth < 6 m was deemed suitable for the growth of desert riparian forests. This results provide a scientific reference for the ecological restoration and protection for Tugai forests in arid areas., Competing Interests: The authors have declared that no competing interests exist.

Objective: Altered expression of caveolin-1 (CAV1) and autophagy marker ATG4C is observed in various types of human cancers. However, the clinical significance of CAV1 and ATG4C expression in epithelial ovarian cancer (EOC) remains largely unknown. The present study aims to explore the clinicopathological value and prognostic significance of CAV1 and ATG4C expression in EOC., Methods: The expression pattern and prognostic value of CAV1 and ATG4C mRNA in EOC were analyzed using data from the Cancer Genome Atlas (TCGA) database (N = 373). In addition, immunohistochemistry analysis was performed to detect and assay the expression of CAV1 and ATG4C proteins in tissue microarray of EOC., Results: Based on TCGA data, Kaplan-Meier analysis indicated that patients with low CAV1 mRNA (p = 0.021) and high ATG4C mRNA (p = 0.018) expression had a significantly shorter overall survival (OS). Cox regression analysis demonstrated that the expression levels of CAV1 (p = 0.023) and ATG4C mRNA (p = 0.040) were independent prognostic factors for OS in EOC. In addition, the Concordance Index of the nomogram for OS prediction was 0.660. Immunohistochemical analysis showed the expression levels of stromal CAV1 and cancerous ATG4C proteins, and high expression of both CAV1 and ATG4C protein in the stroma were found to significantly correlate with the histologic subtypes of EOC, especially with serous subtype., Conclusions: Decreased expression of CAV1 mRNA and increased expression of ATG4C mRNA in EOC can predict poor overall survival. The expression levels of CAV1 protein in stromal cells and ATG4C protein in cancer cells are significantly associated with histologic subtypes of EOC. These findings suggest that CAV1 and ATG4C serve as useful prognostic biomarkers and candidate therapeutic targets in EOC., Competing Interests: he authors have declared that no competing interests exist.

Deep learning methods are being increasingly widely used in static malware detection field because they can summarize the feature of malware and its variants that have never appeared before. But similar to the picture recognition model, the static malware detection model based on deep learning is also vulnerable to the interference of adversarial samples. When the input feature vectors of the malware detection model is based on static features of Windows PE (Portable Executable, PE) file, the model is vulnerable to gradient-based attacks. Regarding the issue above, a method of adversarial sample generation is proposed, which can summarize the blind spots of the original detection model. However, the existing malware adversarial sample generation method is not universal and low in generation efficiency due to the need for human control and difficulty in maintaining a normal file format. In response to these problems, this paper proposes a novel method of automatic adversarial samples generation based on deep reinforcement learning. Firstly, a static PE malware detection model based on deep learning called DeepDetectNet is constructed, the original AUC of which can reach 0.989. Then, an adversarial sample generation model based on reinforcement learning called RLAttackNet is implemented, which generates malware samples that can bypass DeepDetectNet. Finally, when we re-input the adversarial samples into the previously trained DeepDetectNet, the original defects of DeepDetectNet can be reinforced. Experimental results show that the RLAttackNet proposed in this paper can generate about 19.13% of malware samples bypass DeepDetectNet. When DeepDetectNet is retrained with these adversarial samples, the AUC value improves from 0.989 to 0.996 and attack success rate has a significant drop, from 19.13% to 3.1%, compared with the original model., Competing Interests: The authors have declared that no competing interests exist.

Background and Aim: To evaluate the effect of intermittent pringle maneuver (IPM) on the long-term prognosis and recurrence of hepatocellular carcinoma (HCC)., Methods: Eligible studies were identified by PubMed and other databases from Jan 1st 1990 to Mar 31st 2019. Hazard ratios (HR) with 95% confidence interval (CI) were calculated to evaluate the effects of IPM on the long-term prognosis and recurrence of patients with HCC., Results: Six studies were enrolled in this meta-analysis. Results showed that there were no differences between IPM group and non-IPM group in the pooled HRs for the overall survival (OS) and disease-free survival (DFS) (HR 1.04, 95%CI 0.84~1.28, P = 0.74; HR 0.93, 95%CI 0.81~1.07, P = 0.29; respectively). However, subgroup analysis showed that the pooled Odd ratios (OR) for the 1-year OS and DFS rates of the IPM group when compared with the non-IPM group were 0.65 (95% CI 0.45~0.94, P = 0.02), 0.38 (95% CI 0.20~0.72, P = 0.003), respectively. In addition, there were no significant differences in the proportions of liver cirrhosis, HBsAg (+), Child-Pugh A class, multiple tumor, vascular invasion, and major hepatectomy between groups of IPM and non-IPM., Conclusion: Since IPM would increase the risk of early-recurrence, it should be used cautiously in the procedure of hepatectomy for resectable HCC. However, the current conclusion needs further validation., Trial Registry Number: CRD 42019124923., Competing Interests: The authors have declared that no competing interests exist.

Backgroud: Resection is still the only potentially curative treatment for patients with intrahepatic cholangiocarcinoma (ICC), but the prognosis remains far from satisfactory. However, the benefit of adjuvant therapy (AT) remains controversial, although it has been conducted prevalently. Hence, a meta-analysis was warranted to evaluate the effect of AT for patients with ICC after resection., Patients and Methods: PubMed, MedLine, Embase, the Cochrane Library, Web of Science were used to identify potentially eligible studies from Jan.1st 1990 to Aug. 31st 2019, investigating the effect of AT for patients with ICC after resection. Primary endpoint was overall survival (OS), and secondary endpoints was recurrence-free survival (RFS). Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size., Results: 22 studies with 10181 patients were enrolled in this meta-analysis, including 832 patients in the chemotherapy group, 309 patients in the transarterial chemoembolization (TACE) group, 1192 patients in the radiotherapy group, 235 patients in the chemoradiotherapy group, and 6424 patients in the non-AT group. The pooled HR for the OS rate and RFS rate in the AT group were 0.63 (95%CI 0.52~0.74), 0.74 (95%CI 0.58~0.90), compared with the non-AT group. Subgroup analysis showed that the pooled HR for the OS rate in the AT group compared with non-AT group were as follows: chemotherapy group was 0.57 (95%CI = 0.44~0.70), TACE group was 0.56 (95%CI = 0.31~0.82), radiotherapy group was 0.71 (95%CI = 0.39~1.03), chemoradiotherapy group was 0.73 (95%CI = 0.57~0.89), positive resection margin group was 0.60 (95%CI = 0.51~0.69), and lymph node metastasis (LNM) group was 0.67 (95%CI = 0.57~0.76)., Conclusion: With the current data, we concluded that AT such as chemotherapy, TACE and chemoradiotherapy could benefit patients with ICC after resection, especially those with positive resection margin and LNM, but the conclusion needed to be furtherly confirmed., Competing Interests: NO authors have competing interests

Background: The respiratory syncytial virus (RSV) is the main cause of bronchiolitis in infants and interferon (IFN) α is a commercial antiviral drug. The nebulization of IFN α1b could be a viable treatment method. In this study, the therapeutic effects and safety of IFN α1b delivery via nebulization in infant bronchiolitis were investigated in this multi-center prospective study., Methods and Findings: Bronchiolitis patients admitted to 22 hospitals who met the inclusion criteria were enrolled and randomly allocated to four groups: control, IFN Intramuscular Injection, IFN Nebulization 1 (1 μg/kg), and IFN Nebulization 2 (2 μg/kg) groups. All patients were observed for 7 days. The therapeutic effects and safety of different IFN delivery doses and delivery modes were evaluated. Coughing severity change, as scored by the researchers and parents, between days 1 and 3 was significantly different between the IFN Nebulization 2 and control groups. Lowell wheezing score change between days 3 and 5 was significantly different between IFN Nebulization 1 and control groups. There were no significant differences among the four groups regarding the number of consecutive days with fever, three-concave sign, fatigue and sleepiness, and loss of appetite. There were no cases of severe complications, no recurrence of fever, and no regression of mental status., Conclusions: IFN-α1b could more effectively alleviate coughing and wheezing in bronchiolitis. IFN-α1b nebulization had significant advantages in shortening the duration of wheezing and alleviating coughing., Competing Interests: LC was funded by the Support Program of Science & Technology Department of Sichuan Province (No. 2015SZ0152). HL was funded by the Support Program of Science & Technology Department of Sichuan Province (No. 2013SZ0040). The authors have declared that no competing interests exist.

Background: The number of periprosthetic joint infections (PJI) after total knee arthroplasty (TKA) is increasing annually. Animal models have been used to clarify their clinical characteristics and the infection mechanism of pathogenic bacteria, However, since the prosthesis design of animal models is not uniform, it is difficult to simulate the environment of clinical PJI., Objectives: To retrospect the progress on the prosthesis design of animal models of PJI after TKA and to summarize the criteria for evaluating a clinically representative model of PJI., Methods: This systematic review was reported on the basis of Systematic Reviews and Meta-Analyzes (PRISMA). Pubmed, EMbase, Cochrane Library, Web of Science, Wanfang Data and China National Knowledge Infrastructure were researched for animal models of PJI after TKA from database establishment to April 2019 according to Chinese and English retrieval words, including "periprosthetic joint infections and total knee arthroplasty," "periprosthetic joint infections and model," "periprosthetic joint infections and biofilm," and "total knee arthroplasty and model.", Results: A total of 12 quantitative studies were enrolled in our study finally: 8 representative studies described prosthesis designs used in PJI animal models, 4 studies described prosthesis designs in non-infected animal models which were suitable for infection models. The major problems need to be dealed with were prosthesis, installation location, material, the function of separating the articular and medullary cavity, fixation manner, and the procedure of preserving the posterior cruciate ligament., Conclusion: A highly representative design of the animal prosthesis of PJI should meet the following criteria: the surface of the prosthesis is smooth with the formation of biofilm, composed of titanium-6Al-4V or cobalt-chromium-molybdenum alloy; prosthesis can bear weight and is highly stable; and it can connect the joint cavity and medullary cavity simultaneously. To reach a more reliable conclusion, further experiments and improvements are required., Competing Interests: The authors have declared that no competing interests exist.

A new fast busbar protection algorithm based on the comparison of the similarity of back-wave waveforms is proposed in this paper. The S-transform is performed on the back-wave from each defected transmission line connected to the busbar, and the protection criterion is thus constructed by using the Euclidean distance to analyze the similarity of the back-waves, with the implementation of the S-transform between the transmission lines. When a fault occurs internally on the busbar, the Euclidean distance of the S-transformed back-wave between each associated transmission line is small, and there is a remarkable similarity between the waveform. When a fault occurs externally on the busbar, the Euclidean distance of the S-transformed backward traveling wave between the faulty line and the nonfaulty line is larger than that between the nonfaulty lines. The wave-forms of the faulty line and the nonfaulty line bear little similarity, while there is a striking similarity between the nonfaulty lines. Therefore, a protection criterion is established according to the ratio between the maximal similarity and the minimal similarity to discriminate the internal and external faults of the busbar zones. The simulation results show that the proposed busbar protection method can discriminate the internal and external faults of busbar zones in a sensitive and reliable way., Competing Interests: We note that our authors are employed by a commercial company: State Grid Sichuan Electric Power Company. We confirm that our commercial affiliation with State Grid Sichuan Electric Power Company does not alter our adherence to PLOS ONE policies on sharing data and materials.