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Background: Parkinson's disease (PD) is a neurodegenerative disorder, primarily characterized by motor impairments. Vitamin D has several regulatory functions in nerve cell survival and gene expression via its receptors. Although research has shown that vitamin D deficiency is prevalent among PD patients, the causal link to PD risk remains unclear. This study aims to investigate the causal relationship between vitamin D and PD using a bidirectional two-sample Mendelian randomization (MR) analysis method., Methods: This study applied a bidirectional two-sample MR analysis to explore the causal link between vitamin D and PD. We selected statistically significant single nucleotide polymorphisms (SNPs) related to 25-hydroxyvitamin D (25(OH)D) as instrumental variables (IVs), ensuring no association with known confounders. The analysis used GWAS data from over 1.2 million Europeans across four major published datasets, elucidating the genetic correlation between vitamin D levels and PD., Results: We identified 148 instrumental SNPs associated with 25(OH)D. After adjustment for confounding-related SNPs, 131 SNPs remained in the analysis. Data from three PD cohorts revealed no significant correlation between 25(OH)D levels and PD risk using the IVW method (Pcohort1 = 0.365, Pcohort2 = 0.525, Pcohort3 = 0.117). The reverse MR analysis indicated insufficient evidence of PD causing decreased vitamin D levels (P = 0.776)., Conclusion: This is the first study to use bidirectional MR across three PD cohorts to investigate the causal relationship between vitamin D and PD. The results indicate that vitamin D levels are not significantly causally related to PD risk at the genetic level. Therefore, future studies should exercise caution when investigating the relationship between vitamin D levels and PD risk. While no direct causal link exists between vitamin D levels and PD, this does not preclude the potential of vitamin D levels as a biomarker for PD diagnosis. Furthermore, larger-scale longitudinal studies are necessary to evaluate the diagnostic and predictive value of vitamin D levels in PD., 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.)

To analyze the results of proficiency testing for anti-tuberculosis drug susceptibility testing (DST) in China. Number of laboratory participating the proficiency testing performed DST, and the sensitivity, specificity, reproducibility, and accordance rate were calculated from data of 13 rounds proficiency testing results for DST from 2008 to 2021. A total of 30 and 20 strains of Mycobacterium tuberculosis with known susceptibility results were sent to each laboratory in 2008 to 2019, 2020 and 2021, respectively. The number of participating laboratories ranged from 30 in 2009 to 546 in 2021. L-J DST was the predominant method. The specificity presented relatively higher than sensitivity. Improvement of specificity were observed for all drugs through the years, while sensitivity did not show improvement for amikacin and capreomycin. Accordance rate of pyrazinamide and kanamycin and reproducibility of capreomycin and pyrazinamide were not significantly improved through the years. Most of the participating laboratories significantly improved the quality of their DST through the consecutive rounds of proficiency testing except for second-line injectable drugs and pyrazinamide. The results highlight the importance of developing novel and/or improving existing methods for phenotypic DST for certain drugs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Song 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.)

We developed an inherently interpretable multilevel Bayesian framework for representing variation in regression coefficients that mimics the piecewise linearity of ReLU-activated deep neural networks. We used the framework to formulate a survival model for using medical claims to predict hospital readmission and death that focuses on discharge placement, adjusting for confounding in estimating causal local average treatment effects. We trained the model on a 5% sample of Medicare beneficiaries from 2008 and 2011, based on their 2009-2011 inpatient episodes (approximately 1.2 million), and then tested the model on 2012 episodes (approximately 400 thousand). The model scored an out-of-sample AUROC of approximately 0.75 on predicting all-cause readmissions-defined using official Centers for Medicare and Medicaid Services (CMS) methodology-or death within 30-days of discharge, being competitive against XGBoost and a Bayesian deep neural network, demonstrating that one need-not sacrifice interpretability for accuracy. Crucially, as a regression model, it provides what blackboxes cannot-its exact gold-standard global interpretation, explicitly defining how the model performs its internal "reasoning" for mapping the input data features to predictions. In doing so, we identify relative risk factors and quantify the effect of discharge placement. We also show that the posthoc explainer SHAP provides explanations that are inconsistent with the ground truth model reasoning that our model readily admits., Competing Interests: The authors have declared that no competing interests exist., (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.)

Modern healthcare has a sharp focus on data aggregation and processing technologies. Consequently, from a data perspective, a patient may be regarded as a timestamped list of medical conditions and their corresponding corrective interventions. Technologies to securely aggregate and access data for individual patients in the quest for precision medicine have led to the adoption of Digital Twins in healthcare. Digital Twins are used in manufacturing and engineering to produce digital models of physical objects that capture the essence of device operation to enable and drive optimization. Thus, a patient's Digital Twin can significantly improve health data sharing. However, creating the Digital Twin from multiple data sources, such as the patient's electronic medical records (EMR) and personal health records (PHR) from wearable devices, presents some risks to the security of the model and the patient. The constituent data for the Digital Twin should be accessible only with permission from relevant entities and thus requires authentication, privacy, and provable provenance. This paper proposes a blockchain-secure patient Digital Twin that relies on smart contracts to automate the updating and communication processes that maintain the Digital Twin. The smart contracts govern the response the Digital Twin provides when queried, based on policies created for each patient. We highlight four research points: access control, interaction, privacy, and security of the Digital Twin and we evaluate the Digital Twin in terms of latency in the network, smart contract execution times, and data storage costs., Competing Interests: The authors of the article declare that there are no competing interests., (Copyright: © 2024 Amofa 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.)

Purpose: This study aimed to investigate the cost-effectiveness of stent retriever (SR) versus best medical management (BMM) in patients with basilar artery occlusion (BAO) in China., Methods: We used a two-step approach to compare the cost-effectiveness of SR plus BMM with that of BMM alone over 20 years. A decision tree was initially constructed for the first 3 months, followed by a Markov model for the subsequent period. Collected data on clinical aspects were extracted from the BAOCHE investigation, while costs-related information was sourced from previously published research. The key metric for evaluating the primary outcome was the incremental cost-effectiveness ratio (ICER), achieved $/QALY. The threshold for identifying SR as highly cost-effective was set at an ICER below $12,551/QALY, SR was deemed cost-effective if the ICER ranged from $12,551 to $37,654 per QALY. Uncertainty was addressed using scenario, one-way sensitivity, and probabilistic sensitivity analyses (PSA)., Findings: For Chinese patients with BAO, the 20-year cost per patient was $8678 with BMM alone and $21,988 for SR plus BMM. Effectiveness was 1.45 QALY for BMM alone, and 2.77 QALY for SR plus BMM. The ICER of SR + BMM versus BMM alone was $10,050 per QALY. The scenario and one-way sensitivity analyses revealed that in certain situations the ICER could exceed $12,551 per QALY, but remain below $37,654 per QALY. Results from the PSA suggested that SR was likely to be cost-effective for Chinese patients with BAO, with a probability exceeding 98% when considering a willingness-to-pay (WTP) threshold of $12,551 per QALY., Implications: Our study indicates that SR is an intervention option that is highly likely to be cost-effective for Chinese patients with BAO, with a probability of over 98% under the current WTP threshold of $12,551 per QALY., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xia 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.)

Plants play a very important role in landscape construction. In order to explore whether different living environment will affect people's preference for the structural features of plant organs, this study examined 26 villagers and 33 college students as the participants, and pictures of leaves, flowers and fruits of plants as the stimulus to conduct eye-tracking and EEG detection experiments. We found that eye movement indicators can explain people's visual preferences, but they are unable to find differences in preferences between groups. EEG indicators can make up for this deficiency, which further reveals the difference in psychological and physiological responses between the two groups when viewing stimuli. The final results show that the villagers and the students liked leaves best, preferring aciculiform and leathery leaves; solitary, purple and capitulum flowers; and medium-sized, spathulate, black and pear fruits. In addition, it was found that the overall attention of the villagers when watching stimuli was far lower than that of the students, but the degree of meditation was higher. With regard to eye movement and EEG, the total duration of fixations is highly positively correlated with the number of fixations, and the average pupil size has a weak negative correlation with attention. On the contrary, the average duration of fixations has a weak positive correlation with meditation. Generally speaking, we believe that Photinia×fraseri, Metasequoia glyptostroboides, Photinia serratifolia, Koelreuteria bipinnata and Cunninghamia lanceolata are superior landscape building plants in rural areas and on campuses; Pinus thunbergii, Myrica rubra, Camellia japonica and other plants with obvious features and bright colours are also the first choice in rural landscapes; and Yulania biondii, Cercis chinensis, Hibiscus mutabilis and other plants with simple structures are the first choice in campus landscapes. This study is of great significance for selecting plants for landscape construction and management according to different environments and local conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Ding 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 purpose of this paper is to explore the spatial heterogeneity of internal migration in China and to discuss the influence of economic, social and environmental characteristics on this demographic process. The overall results suggest that migration in China occurred from inland to coastal areas and from rural areas to urban areas. By stepwise regression, we identified that 9 out of 15 factors with potential influence on internal migration were retained, and the multicollinearity among them was reduced. In addition, we used the OLS and GWR regression analysis to discuss the global and local effects of relevant factors on internal migration. Economic scale (GDP), population concentration (population density) and demographic dividend (labour force proportion) were the three main driving forces of internal migration. In turn, internal migration further widened the gap of economic scale, population agglomeration and demographic dividend between counties and cities. Internal migration in southern coastal areas of China was most affected by economic aspects and demographic dividend. In the central China, the population was more concentrated in high-density cities, while in the eastern regions, areas with high level of education were conducive to immigration, thus forming talent reserve highlands. In the west, areas with highly educated level faced out-migration, which might cause brain drain and widen further the gap in talent reserves between the east and the west in China. From the perspective of location, the net immigration of the provincial capital was accompanied by the net immigration of the surrounding area, which was conducive to the formation of city clusters or urban sprawl. On the other side, the net immigration in prefecture-level cities often meant the net out-migration in surrounding areas. The correlation is particularly strong in eastern coastal provinces., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Xia 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 and Aims: At present, it is difficult and risky to diagnose splenic lesions by conventional needle biopsy using computed tomography (CT) or ultrasound (US). Endoscopic ultrasound (EUS)-guided tissue acquisition is increasingly being used as a new technique to determine the tissue diagnosis of splenic lesions. Therefore, our goal was to determine the efficacy and safety of EUS-guided tissue acquisition for splenic lesions., Methods: We performed a systematic review and meta-analysis to evaluate the pooled sensitivity and specificity of EUS-guided tissue acquisition for the diagnosis of splenic lesions using Metadisc. The Quality Assessment of Diagnostic Accuracy Studies Questionnaire, a quality assessment tool, was used to scrutinize the quality of the studies., Results: Six eligible studies between January 2000 and June 2022 were identified, and a total number of 62 patients (aged range from 19 to 84) were enrolled. One patient was excluded because of insufficient specimens. The pooled sensitivity and specificity of included studies were 0.85 [95% confidence interval (CI), 0.73-0.93] and 0.77 (95% CI, 0.46-0.95), respectively. The pooled positive likelihood ratio (LR) was 2.38 (95% CI, 1.24-4.57), the pooled negative LR was 0.31 (95% CI, 0.17-0.55), the pooled diagnostic odds ratio (DOR) was 8.67 (95% CI, 2.80-26.82), the area under the summary receiver operating characteristic (SROC) curve was 0.8100 (Standard Error 0.0813)., Conclusion: EUS-guided tissue acquisition is a safe technique with high sensitivity in the diagnosis of splenic lesions. However, because of the small sample sizes, more studies with more cases are needed to further validate these results., Competing Interests: The authors have declared that no competing interests exist.

Background: Psittacosis pneumonia is a community-acquired pneumonia caused by Chlamydia psittaci. It is usually under-diagnosed due to its atypical clinical presentation and lack of routine laboratory tests., Methods: To better understand the clinical features, 52 patients diagnosed with psittacosis pneumonia by metagenomic next-generation sequencing (mNGS) were enrolled in this study. The clinical, radiological and pathological characteristics were retrospectively analyzed., Results: The onset of psittacosis pneumonia in this study occurred all year round, with a peak from December to January. Most of the patients were 51-80 years old. About 65.38% of patients had a history of exposure to poultry or parrots. Abnormalities of multiple clinical signals were detected in these patients. Elevated levels of neutrophil ratio, C-reactive protein, erythrocyte sedimentation rate, and procalcitonin were detected in most patients. Radiological evidence revealed air-space consolidation or ground-glass opacities in lungs of all patients, which is the typical feature of psittacosis pneumonia. In addition, hyperemia, swelling of bronchial mucosa, and bronchial patency were detected by bronchoscopy in all patients, and bronchial sub-mucosal edema, inflammatory cells infiltration and alveolar epithelial hyperplasia were identified in the bronchial mucosa and alveolar tissue. Beta-lactam antibiotics were administered for empirical treatment before mNGS in 17 patients but showed no improvement. The treatment was switched to doxycycline or moxifloxacin immediately since psittacosis pneumonia were suspected and confirmed by mNGS detection (within 48 hours). After receiving adjustment of treatment, 94.23% (49/52) of patients were cured successfully., Conclusions: In conclusion, mNGS may be a promising approach for clinical diagnosis of psittacosis. For patients with a history of exposure to birds, hyperpyrexia, nonproductive cough, multiple elevated inflammatory markers, and air-space consolidation in lung, psittacosis pneumonia should be considered, especially when beta-lactam antibiotics showed limited efficacy., Competing Interests: The authors have declared that no competing interests exist.

Genomic surveillance empowers agile responses to SARS-CoV-2 by enabling scientists and public health analysts to issue recommendations aimed at slowing transmission, prioritizing contact tracing, and building a robust genomic sequencing surveillance strategy. Since the start of the pandemic, real time RT-PCR diagnostic testing from upper respiratory specimens, such as nasopharyngeal (NP) swabs, has been the standard. Moreover, respiratory samples in viral transport media are the ideal specimen for SARS-CoV-2 whole-genome sequencing (WGS). In early 2021, many clinicians transitioned to antigen-based SARS-CoV-2 detection tests, which use anterior nasal swabs for SARS-CoV-2 antigen detection. Despite this shift in testing methods, the need for whole-genome sequence surveillance remains. Thus, we developed a workflow for whole-genome sequencing with antigen test-derived swabs as an input rather than nasopharyngeal swabs. In this study, we use excess clinical specimens processed using the BinaxNOW™ COVID-19 Ag Card. We demonstrate that whole-genome sequencing from antigen tests is feasible and yields similar results from RT-PCR-based assays utilizing a swab in viral transport media., Competing Interests: The authors have declared that no competing interests exist.

Tendinopathy is a complex multifaceted tendinopathy often associated with overuse and with its high prevalence resulting in significant health care costs. At present, the pathogenesis and effective treatment of tendinopathy are still not sufficiently elucidated. The purpose of this research is to intensely explore the genes, functional pathways, and immune infiltration characteristics of the occurrence and development of tendinopathy. The gene expression profile of GSE106292, GSE26051 and GSE167226 are downloaded from GEO (NCBI comprehensive gene expression database) and analyzed by WGCNA software bag using R software, GSE26051, GSE167226 data set is combined to screen the differential gene analysis. We subsequently performed gene enrichment analysis of Gene Ontology (GO) and "Kyoto Encyclopedia of Genes and Genomes" (KEGG), and immune cell infiltration analysis. By constructing the LASSO regression model, Support vector machine (SVM-REF) and Gaussian mixture model (GMMs) algorithms are used to screen, to identify early diagnostic genes. We have obtained a total of 171 DEGs through WGCNA analysis and differentially expressed genes (DEGs) screening. By GO and KEGG enrichment analysis, it is found that these dysregulated genes were related to mTOR, HIF-1, MAPK, NF-κB and VEGF signaling pathways. Immune infiltration analysis showed that M1 macrophages, activated mast cells and activated NK cells had infiltration significance. After analysis of THE LASSO SVM-REF and GMMs algorithms, we found that the gene MACROD1 may be a gene for early diagnosis. We identified the potential of tendon disease early diagnosis way and immune gene regulation MACROD1 key infiltration characteristics based on comprehensive bioinformatics analysis. These hub genes and functional pathways may as early biomarkers of tendon injuries and molecular therapy level target is used to guide drug and basic research., Competing Interests: The authors have declared that no competing interests exist.

The internal flow and macroscopic spray behaviors of a fuel injection process were studied with schlieren spray techniques and simulations. The injection pressures(Pin)and ambient pressures(Pout)were applied in a wide range. The results showed that increasing the Pin is likely to decrease the flow performance of the nozzle. Furthermore, increasing the Pin can increase the spray tip penetration. However, the effect of Pin on the spray cone angle was not evident. The spray cone angle at an injection pressure of 160MPa was 21.7% greater than at a pressure of 100MPa during the initial spraying stage. Additionally, the discharge coefficient increased under high Pout, and the decrease in Pout can promote the formation of cavitation. Finally, increasing the Pout can decrease the penetration, while the spray angle becomes wider, especially at the initial spray stage, and high Pout will enhance the interaction of the spray and the air, which can enhance the spray quality., Competing Interests: The authors have declared that no competing interests exist.

The efficacy of cranberry (Vaccinium spp.) as adjuvant therapy in preventing urinary tract infections (UTIs) remains controversial. This study aims to update and determine cranberry effects as adjuvant therapy on the recurrence rate of UTIs in susceptible groups. According to PRISMA guidelines, we conducted a literature search in Web of Science, PubMed, Embase, Scopus, and the Cochrane Library from their inception dates to June 2021. We included articles with data on the incidence of UTIs in susceptible populations using cranberry-containing products. We then conducted a trial sequential analysis to control the risk of type I and type II errors. This meta-analysis included 23 trials with 3979 participants. We found that cranberry-based products intake can significantly reduce the incidence of UTIs in susceptible populations (risk ratio (RR) = 0.70; 95% confidence interval(CI): 0.59 ~ 0.83; P<0.01). We identified a relative risk reduction of 32%, 45% and 51% in women with recurrent UTIs (RR = 0.68; 95% CI: 0.56 ~ 0.81), children (RR = 0.55; 95% CI: 0.31 ~ 0.97) and patients using indwelling catheters (RR = 0.49; 95% CI: 0.33 ~ 0.73). Meanwhile, a relative risk reduction of 35% in people who use cranberry juice compared with those who use cranberry capsule or tablet was observed in the subgroup analysis (RR = 0.65; 95% CI: 0.54 ~ 0.77). The TSA result for the effects of cranberry intake and the decreased risk of UTIs in susceptible groups indicated that the effects were conclusive. In conclusion, our meta-analysis demonstrates that cranberry supplementation significantly reduced the risk of developing UTIs in susceptible populations. Cranberry can be considered as adjuvant therapy for preventing UTIs in susceptible populations. However, given the limitations of the included studies in this meta-analysis, the conclusion should be interpreted with caution., Competing Interests: The authors have declared that no competing interests exist.

Uricase-deficient rats could be one of the optimal model animals to study hyperuricemia. The present study aimed to find the biological differences between uricase-deficient (Kunming-DY rats) and wild-type male rats. Uricase-deficient rats and wild-type rats were commonly bred. Their body weight, water and food consumption, 24-h urine and feces, uric acid in serum and organs, and serum indexes were recorded or assayed. Organs, including the heart, liver, spleen, lung, kidney, thymus, stomach, duodenum, and ileum, were examined using a routine hematoxylin-eosin staining assay. We found that the growth of male uricase-deficient rats was retarded. These rats excreted more urine than the wild-type rats. Their organ indexes (organ weight body weight ratio), of the heart, liver, kidney, and thymus significantly increased, while those of the stomach and small intestine significantly decreased. The uricase-deficient rats had a significantly higher level of serum uric acid and excreted more uric acid via urine at a higher concentration. Except for the liver, uric acid increased in organs and intestinal juice of uricase-deficient rats. Histological examination of the uricase-deficient rats showed mild injuries to the heart, liver, spleen, lung, kidney, thymus, stomach, duodenum, and ileum. Our results suggest that uricase-deficient rats have a different biological pattern from the wild-type rats. Uricase deficiency causes growth retardation of young male rats and the subsequent increase in serum uric acid results in mild organs injuries, especially in the kidney and liver., Competing Interests: The authors have declared that no competing interests exist.

Heterotaxy (HTX), a condition characterized by internal organs not being arranged as expected relative to each other and to the left-right axis, is often accompanied with congenital heart disease (CHD). The purpose was to detect the pathogenic variants in a Chinese family with HTX and CHD. A non-consanguineous Han Chinese family with HTX and CHD, and 200 unrelated healthy subjects were enlisted. Exome sequencing and Sanger sequencing were applied to identify the genetic basis of the HTX family. Compound heterozygous variants, c.3426-1G>A and c.4306C>T (p.(Arg1436Trp)), in the dynein axonemal heavy chain 11 gene (DNAH11) were identified in the proband via exome sequencing and further confirmed by Sanger sequencing. Neither c.3426-1G>A nor c.4306C>T variant in the DNAH11 gene was detected in 200 healthy controls. The DNAH11 c.3426-1G>A variant was predicted as altering the acceptor splice site and most likely affecting splicing. The DNAH11 c.4306C>T variant was predicted to be damaging, which may reduce the phenotype severity. The compound heterozygous variants, c.3426-1G>A and c.4306C>T, in the DNAH11 gene might be the pathogenic alterations resulting in HTX and CHD in this family. These findings broaden the variant spectrum of the DNAH11 gene and increase knowledge used in genetic counseling for the HTX family., Competing Interests: The authors have declared that no competing interests exist.

Background: COVID-19 is a respiratory infectious disease caused by SARS-CoV-2, and cardiovascular damage is commonly observed in affected patients. We sought to investigate the effect of SARS-CoV-2 infection on cardiac injury and hypertension during the current coronavirus pandemic., Study Design and Methods: The clinical data of 366 hospitalized COVID-19-confirmed patients were analyzed. The clinical signs and laboratory findings were extracted from electronic medical records. Two independent, experienced clinicians reviewed and analyzed the data., Results: Cardiac injury was found in 11.19% (30/268) of enrolled patients. 93.33% (28/30) of cardiac injury cases were in the severe group. The laboratory findings indicated that white blood cells, neutrophils, procalcitonin, C-reactive protein, lactate, and lactic dehydrogenase were positively associated with cardiac injury marker. Compared with healthy controls, the 190 patients without prior hypertension have higher AngⅡ level, of which 16 (8.42%) patients had a rise in blood pressure to the diagnostic criteria of hypertension during hospitalization, with a significantly increased level of the cTnI, procalcitonin, angiotensin-II (AngⅡ) than those normal blood pressure ones. Multivariate analysis indicated that elevated age, cTnI, the history of hypertension, and diabetes were independent predictors for illness severity. The predictive model, based on the four parameters and gender, has a good ability to identify the clinical severity of COVID-19 in hospitalized patients (area under the curve: 0.932, sensitivity: 98.67%, specificity: 75.68%)., Conclusion: Hypertension, sometimes accompanied by elevated cTnI, may occur in COVID-19 patients and become a sequela. Enhancing Ang II signaling, driven by SARS-CoV-2 infection, might play an important role in the renin-angiotensin system, and consequently lead to the development of hypertension in COVID-19., Competing Interests: The authors report no relationships that could be construed as a conflict of interest.

Understanding the response mechanism of ecosystems to climate change and human disturbance can be improved by analyzing the spatial patterns of vegetation phenology and its influencing factors. Because the diverse phenological patterns are impacted by cloud cover contamination issues in the satellite observations, there are few remote sensing phenological research data in subtropical monsoon climate regions. To better understand the horizontal and vertical changes of vegetation phenology in these regions and how it may be affected by climatic factors and topographical features, we first extracted vegetation phenological information (such as start of growth season (SOS), end of growth season (EOS) and length of growth season (LEN)) from a reconstructed MODIS EVI time-series data. We then used geographic detectors to identify the influencing factors of phenology in different elevation zoning areas. We have found that in the Xiangjiang River Basin: 1) gradual changes in the longitudinal or latitudinal gradient of vegetation phenology were not obvious. Instead of horizontal changes, the variation pattern of phenology was similar to the striped river network of the Xiangjiang River. Earlier SOS mainly appeared in the areas far away from the river; later SOS appeared in the midstream and downstream reaches.2) Elevation played an important role in the regional differentiation of phenology. Boundaries at elevations of 320 m and 520 m distinctly separated the region into plain, hilly, and mountain vegetation phenological characteristics. 3) The impacts of climatic factors were quite different in the three vertical zoning areas. Precipitation was the most crucial factor affecting SOS both in plain and mountain areas. There was no significant factor affecting EOS in the plain area, but temperature had an essential effect on EOS in the mountain area. The hilly areas had a concentrated growth period with no significant factors affecting phenology. These findings highlight the importance of elevation in phenology at a watershed scale, enhance our understanding of the impact of climate changes on subtropical ecosystems, and provide a reference for further land-use change monitoring., Competing Interests: The authors have declared that no competing interests exist.

The purpose of this study was to detect nutrient uptake and assimilation in woody plants subjected to growing media with some peat replaced by spent mushroom residue (SMR). Fragrant rosewood (Dalbergia odorifera T.C. Chen) seedlings were cultured in five types of growing media with SMR and peat in volumetric proportions of 0% (control), 25%, 50%, 75%, and 100%. With the increase of SMR proportion, ammonium- and nitrate-nitrogen (N) concentrations declined but available phosphorus (P) concentration and electrical conductance both increased. Seedlings in the full SMR substrates showed obvious mortality. Seedlings in substrates with SMR in proportions higher than 25% showed symptoms of excessive N and P toxicities. The utilization efficiency for P was highest in the 25% SMR growing-media. Mineral N in substrates had a positive relationship with growth and biomass but not with glutamine synthetase activity. Available P was negatively related with acid phosphatase activity in both leaves and roots. Un-composted SMR can replace 25% of peat in growing media for fragrant rosewood seedlings, benefitting P uptake and assimilation., Competing Interests: The authors have declared that no competing interests exist.

Due to the rapid economic growth and the heavy reliance on fossil fuels, China has become one of the countries with the highest sulfur dioxide (SO2) emissions, which pose a severe challenge to human health and the sustainable development of social economy. In order to cope with the serious problem of SO2 pollution, this study attempts to explore the spatial temporal variations of industrial SO2 emissions in China utilizing the Defense Meteorological Satellite Program's Operational Linescan System (DMSP-OLS) nighttime stable light (NSL) data. We first explored the relationship between the NSL data and the statistical industrial SO2 emissions at the provincial level, and confirmed that there was a positive correlation between these two datasets. Consequently, 17 linear regression models were established based on the NSL data and the provincial statistical emissions to model the spatial-temporal dynamics of China's industrial SO2 emissions from 1997 to 2013. Next, the NSL-based estimated results were evaluated utilizing the prefectural statistical industrial SO2 emissions and emission inventory data, respectively. Finally, the distribution of China's industrial SO2 emissions at 1 km spatial resolution were estimated, and the temporal and spatial dynamics were explored from multiple scales (national scale, regional scale and scale of urban agglomeration). The results show that: (1) The NSL data can be successfully applied to estimate the dynamic changes of China's industrial SO2 emissions. The coefficient of determination (R2) values of the NSL-based estimation results in most years were greater than 0.6, and the relative error (RE) values were less than 10%, when validated by the prefectural statistical SO2 emissions. Moreover, compared with the inventory emissions, the adjusted coefficient of determination (Adj.R-Square) reached 0.61, with the significance at the 0.001 level. (2) During the observation period, the temporal and spatial dynamics of industrial SO2 emissions varied greatly in different regions. The high growth type was largely distributed in China's Western region, Central region, and Shandong Peninsula, while the no-obvious-growth type was concentrated in Western region, Beijing-Tianjin-Tangshan and Middle south of Liaoning. The high grade of industrial SO2 emissions was mostly concentrated in China's Eastern region, Western region, Shanghai-Nanjing-Hangzhou and Shandong Peninsula, while the low grade mainly concentrated in China's Western region, Middle south of Liaoning and Beijing-Tianjin-Tangshan. These results of our research can not only enhance the understanding of the spatial-temporal dynamics of industrial SO2 emissions in China, but also offer some scientific references for formulating feasible industrial SO2 emission reduction policies., Competing Interests: The authors have declared that no competing interests exist.

Diet is believed to play a major role in maternal recovery, postpartum weight retention (PPWR) is one of the challenges for Chinese women. However, the association between puerperal women's diet and PPWR remained unclear and complicated in China. The study assessed the dietary quality of puerperal women using adjusted Chinese Dietary Balance Index-16 (DBI-16) and explored its associations with PPWR. Participants were enrolled in the Mother-Infant Cohort Study of China. Dietary intake and demographic characteristics were obtained by a semi-quantitative food frequency questionnaire and a self-designed questionnaire at 0-3 months postpartum. PPWR was calculated by the weight difference at 0-3months and 6-8months postpartum minus pre-pregnancy weight. Dietary quality was assessed using adjusted DBI-16. 316 puerperal women were enrolled. According to adjusted DBI-16, 84.8% of participants had an insufficient dietary intake (vegetables 84.8%, fruits 91.8%, dairy 87.3%, soybean 61.4% and aquatic foods 79.4%, respectively), 67.1% had an excessive intake (cereals 60%, meat 57.3% and eggs 64.9%, respectively), 98.4% had an imbalanced diet consumption. PPWR at 0-3, and 6-8 months were 6.0 (±5.1) kg and 5.2 (±7.7) kg, and the percentage of PPWR (≥5kg) were 63.0% and 52.8% respectively. Multivariable linear regression showed the intake of fish and shrimp at 0-3 months postpartum was negatively associated with PPWR at 6-8 months (β = -0.114, SE = 0.279, p < 0.05). The diet quality of Chinese puerperal women was unreasonable and imbalanced. Fish intake tended to be a favorable factor for postpartum weight loss., Competing Interests: The authors have declared that no competing interests exist.

Sugarcane (Saccharum spp.) is an important economic crop, supplying up to 80% of the table sugar and ~60% of bio-ethanol worldwide. Due to population growth and dwindling fossil-fuel reserves, the demand for sugar and bio-ethanol requires significant improvement in sugarcane production. Breeding sugarcane cultivars with high-performance agronomic traits is undoubtedly the most efficient way to achieve this goal. Therefore, evaluating agronomic traits and dissecting underlying loci are critically important for this aim steps in providing genetic resources and molecular markers for selection. In this study, we assembled a diversity panel of 236 elite sugarcane germplasms originally collected from 12 countries. We evaluated 28 agronomic traits in the diversity panel with three replicates. The diversity panel was genotyped using amplified fragment length polymorphism markers, and a total of 1,359 markers were generated. Through the genome-wide association study, we identified three markers significantly associated with three traits evaluated at a stringent threshold (P < 0.05 after Bonferroni correction). The genotypes of the three associated markers grouped respective trait values into two distinct groups, supporting the reliability of these markers for breeding selection. Our study provides putative molecular markers linked to agronomic traits for breeding robust sugarcane cultivars. Additionally, this study emphasized the importance of sugarcane germplasm introduced from other countries and suggested that the use of these germplasms in breeding programs depends on local industrial needs., Competing Interests: The authors have declared that no competing interests exist.

Melatonin (MT) has many important functions in plants. In this study, different concentrations of MT (0, 50, 100, 150, and 200 μmol/L) were sprayed on grape seedlings, and its effects on plant growth and sucrose metabolism were determined. The results show that there was a mutual influence and promotional relationship between growth and sugar metabolism in grape seedlings. The MT treatments promoted the development and growth of grape seedlings by increasing their biomass and promoting the photosynthetic performance of leaves. This resulted in increased nutrient absorption and a greater ability to compete for resources. The increase in photosynthesis resulted in greater sucrose production. The MT treatments increased the activities of enzymes related to sucrose metabolism, so that a large amount of sucrose was hydrolysed into glucose and fructose to meet the rapid growth requirements of grape seedlings. The increased total soluble sugars contents and increased activities of antioxidant enzymes resulted in greater resistance of grape seedlings, and greater adaptability to environmental changes. In general, MT treatments had beneficial effects on grape seedling growth, glucose metabolism, and resistance. Under these conditions, foliar spraying with MT at 150 μmol/L had the best effects., Competing Interests: The authors have declared that no competing interests exist.

The performance of VereMTBTM Detection Kit for detection of multidrug-resistant tuberculosis (MDR-TB) was validated by using 124 sputum samples. Comparing with MGIT culture, the sensitivity and specificity of VereMTB Detection Kit for MTBC detection were 97.0% and 98.3%, respectively. Compared with MGIT DST, the sensitivity and specificity of VereMTB Detection Kit for RIF resistance detection were 85.7% and 93.9%, respectively, and the sensitivity and specificity of VereMTB Detection Kit for INH resistance detection were 75.0% and 95.7%, respectively. 6 NTM samples were also detected and identified correctly. The VereMTB Detection Kit can detect MDR-TB rapidly and accurately in sputum samples from TB suspects., Competing Interests: We have the following competing interests: Veredus Laboratories Pte Ltd provided support for this study in the form of VereMTB Detection Kit training, machine adjustment and maintenance. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

How to achieve the sustainable and coordinated development of the ecological environment, the economy and tourism has already received much attention. In this paper, a comprehensive evaluation index system of the ecological environment, the economy and tourism is established, and the coupling degrees and coordination degrees of the three subsystems of 31 provinces in China from 2003 to 2017 are calculated. The results show that the average coupling degree and average coordination degree have fluctuating upward trends during the period of 2003-2017. According to the spatial distribution of the coupling degrees and coordination degrees, the coastal provinces and Chongqing, with their high ecological environment pressure and good economic development, have low coupling and extremely high coordination levels. The vast central and western provinces with good ecological environment protection and economic backwardness have high coupling and low coordination development level. From the perspective of coordinated development, only seven of the western provinces and three middle-eastern provinces possess basic coordinated development of the ecological environment, the economy and tourism. The remaining 21 provinces are over-utilizing or sacrificing their ecological environments, among which eleven eastern provinces have an advanced economy or advanced tourism and five southwestern provinces with high tourism resource endowments have an advanced tourism., Competing Interests: The authors have declared that no competing interests exist.

Background: Pediatric patients undergoing invasive operations bear extra risk of developing nosocomial infections (NIs). However, epidemiological evidence of the underlying risk factors, which is needed for early prevention, remains limited., Methods: Using data from the electronic medical records and the NI reporting system of a tertiary pediatric hospital, we conducted a retrospective analysis to identify preoperative and operation-related risk factors for postoperative NIs. Multivariable accelerated failure time models were fitted to select independent risk factors. The performance of these factors in risk stratification was examined by comparing the empirical risks between the model-defined low- and high-risk groups., Results: A total of 18,314 children undergoing invasive operations were included for analysis. After a follow-up period of 154,700 patient-days, 847 postoperative NIs were diagnosed. The highest postoperative NI rate was observed for operations on hemic and lymphatic system. Surgical site infections were the NI type showing the highest overall risk; however, patients were more likely to develop urinary tract infections in the first postoperative week. Older age, higher weight-for-height z-score, longer preoperative ICU stay, preoperative enteral nutrition, same-day antibiotic prophylaxis, and higher hemoglobin level were associated with delayed occurrence of postoperative NIs, while longer preoperative hospitalization, longer operative duration, and higher American Society of Anesthesiologists score showed acceleration effects. Risk stratification based on these factors in an independent patient population was moderate, resulting in a high-risk group in which 72% of the postoperative NIs were included., Conclusions: Our findings suggest that pediatric patients undergoing invasive operations and at high risk of developing postoperative NIs are likely to be identified using basic preoperative and operation-related risk factors, which together might lead to moderately accurate risk stratification but still provide valuable information to guide early and judicious prevention., Competing Interests: The authors have declared that no competing interests exist.

Over the period 1982-2015, temperatures have exhibited an asymmetric warming pattern diurnally, as well as seasonally across the Loess Plateau. However, very limited research has studied the implications and effects of such seasonally heterogeneous warming across the Loess Plateau. In this study, we also analyzed the time series trends and seasonal spatial patterns of the maximum (Tmax) and minimum (Tmin) temperatures and evaluated how different vegetation responded to daytime and nighttime warming in the Loess Plateau from 1982 to 2015 based on the NDVI and meteorological parameters (precipitation or temperature). We found that Tmax and Tmin significantly increased throughout the years except for Tmax in autumn, and the diurnal asymmetric warming showed some striking seasonal differences. For example, the increasing rates of Tmin in spring, summer, autumn, and winter were 0.75, 1.20, 1.88, and 1.10 times larger than that of Tmax, respectively. NDVI showed significantly positive correlation with Tmax and Tmin in spring and winter, while NDVI presented significantly positive correlation with Tmin in summer and Tmax in autumn across entire Loess Plateau. Furthermore, we also discovered diverse seasonal responses in terms of vegetation types to daytime and nighttime warming. For instance, Spring NDVI showed significantly positive partial correlations with Tmax and Tmin. In summer, grasslands and wetlands merely displayed significantly positive partial correlations with Tmin. Cultivated land presented significantly positive partial correlation between the NDVI and Tmax (Tmin) in autumn. In winter, cultivated land, forest, and grassland exhibited significantly positive partial correlation with Tmax and Tmin, while only wetland showed a significantly positive partial correlation with Tmax. Our results demonstrated responses of vegetation to climate extremes and enhance a better understanding of the seasonally different responses of vegetation under global climate change at different scale., Competing Interests: The authors have declared that no competing interests exist.

The differences in archaeal diversity and community composition in the sediments and waters of the Qinhuangdao coastal aquaculture zone were investigated. Furthermore, the associations between dominant archaeal taxa with geographic and environmental variables were evaluated. High-throughput sequencing of archaeal 16S rRNA genes yielded a total of 176,211 quality-filtered reads and 1,178 operational taxonomic units (OTUs) overall. The most abundant phylum and class among all communities were Thaumarchaeota and Nitrososphaeria, respectively. Beta diversity analysis indicated that community composition was divided into two groups according to the habitat type (i.e., sediments or waters). Only 9.8% OTUs were shared by communities from the two habitats, while 73.9% and 16.3% of the OTUs were unique to sediment or water communities, respectively. Furthermore, the relative abundances of the dominant OTUs differed with habitat type. Investigations of relationships between dominant OTUs and environmental variables indicated that some dominant OTUs were more sensitive to variation in environmental factors, which could be due to individual taxonomic differences in lifestyles and biological processes. Overall, the investigation of archaeal community variation within the Qinhuangdao coastal aquaculture zone provides an important baseline understanding of the microbial ecology in this important ecosystem., Competing Interests: The authors have declared that no competing interests exist.

Coastlines are the boundary between the ocean and land and are an important line feature in spatial data. Coastlines must be adapted via map generalization when they are stored in multi-scale spatial databases. This article presents a new method of coastline generalization that considers the buffer consistency from the original coastline to the generalized coastlines. This method uses the geographical distance field to identify the feature points and bends that influence the buffer consistency from the original coastline to the generalized coastline, and the process is also used to simplify the bends and maintain the concave and convex characteristics in the generalization. This method is compared to the bend-simplification method, and the results indicate that the proposed method can preserve the shape characteristics of coastlines. Moreover, the seaward buffer boundaries from the original coastline to the generalized coastline are consistent when the distance is greater than the tolerance of the coastline generalization., Competing Interests: The authors have declared that no competing interests exist.

Arachis hypogaea L. geocarpy is a unique feature different from other legume plants. Flowering and fertilization occur above ground, while the following processes of pod formation and development proceed in the soil. The zygote divides only few times to develop into pre-embryo and then further embryo developmental process stops when the gynoecium is exposed to light condition or normal day/night period. In this study, eight phytochrome genes were identified in two wild peanuts (four in Arachis duranensis and four in Arachis ipaensis). Using RACE and homologous cloning, the full CDS of AhphyA, AhphyA-like, AhphyB and AhphyE were acquired in cultivated peanut. Protein structure analysis showed that the conservative coding domains of phytochromes from a number of other plant species were found in these proteins. The C-terminal of AhphyA, AhphyA-like and AhphyB could interact with phytochrome-interacting factor 3 in vitro. The expression patterns of these genes in various tissues were analyzed by qRT-PCR, and significant differences were observed. Interestingly, the expression levels of AhphyA-like changed significantly during gynophore growth and early pod development. Furthermore, protein accumulation patterns of AhphyA and AhphyB in gynophore were different during early pod development stages in that AhphyA and AhphyB proteins were not detected in S1 and S2 gynophores, while significant accumulation of AhphyA and AhphyB were detected in S3 gynophore. These results provided evidence that phytochromes mediated light signal transduction may play key roles in peanut geocarpy development., Competing Interests: The authors have declared that no competing interests exist.

Vanillin (4-hydroxy-3-methoxybenzaldehyde), a food additive with rich milk flavor, is commonly used in the food, beverage and cosmetic industries. However, excessive consumption of vanillin may cause liver and kidney damage. Therefore, methods for detecting and controlling the level of vanillin in food, especially in infant powder, have important practical significance. In this study, we established a colorimetric assay for vanillin detection. The detection was performed under high-temperature and acidic conditions, which can induce the reaction of the aldehyde group of vanillin with the amino group of o-toluidine. The resulting product had a maximum absorption at 363 nm, which was quantified by a UV spectrophotometer. This assay had a limit of detection (LOD) of 1 pg mL-1 and a linear range between 1 μg mL-1 and 100 μg mL-1. The average recoveries at three spiked levels were in the range from 91.1% to 101.6% with a relative standard deviation (RSD) of 4.62% ~ 7.27%.

Background: The use of centrifugation-based approaches for processing donated blood into components is routine in the industrialized world, as disparate storage conditions require the rapid separation of 'whole blood' into distinct red blood cell (RBC), platelet, and plasma products. However, the logistical complications and potential cellular damage associated with centrifugation/apheresis manufacturing of blood products are well documented. The objective of this study was to evaluate a proof-of-concept system for whole blood processing, which does not employ electromechanical parts, is easily portable, and can be operated immediately after donation with minimal human labor., Methods and Findings: In a split-unit study (n = 6), full (~500mL) units of freshly-donated whole blood were divided, with one half processed by conventional centrifugation techniques and the other with the new blood separation system. Each of these processes took 2-3 hours to complete and were performed in parallel. Blood products generated by the two approaches were compared using an extensive panel of cellular and plasma quality metrics. Comparison of nearly all RBC parameters showed no significant differences between the two approaches, although the portable system generated RBC units with a slight but statistically significant improvement in 2,3-diphosphoglyceric acid concentration (p < 0.05). More notably, several markers of platelet damage were significantly and meaningfully higher in products generated with conventional centrifugation: the increase in platelet activation (assessed via P-selectin expression in platelets before and after blood processing) was nearly 4-fold higher for platelet units produced via centrifugation, and the release of pro-inflammatory mediators (soluble CD40-ligand, thromboxane B2) was significantly higher for centrifuged platelets as well (p < 0.01)., Conclusion: This study demonstrated that a simple, passive system for separating donated blood into components may be a viable alternative to centrifugation-particularly for applications in remote or resource-limited settings, or for patients requiring highly functional platelet product.

Background: Platelet-derived growth factor receptor alpha (PDGFRα) is a cell-surface receptor tyrosine kinase for platelet-derived growth factors. Correct timing and level of Pdgfra expression is crucial for embryo development, and deletion of Pdgfra caused developmental defects of multiple endoderm and mesoderm derived structures, resulting in a complex phenotypes including orofacial cleft, spina bifida, rib deformities, and omphalocele in mice. However, it is not clear if deletion of Pdgfra at different embryonic stages differentially affects these structures., Purpose: To address the temporal requirement of Pdgfra in embryonic development., Methods: We have deleted the Pdgfra in Pdgfra-expressing tissues at different embryonic stages in mice, examined and quantified the developmental anomalies., Results: Current study showed that (i) conditional deletion of Pdgfra at different embryonic days (between E7.5 and E10.5) resulted in orofacial cleft, spina bifida, rib cage deformities, and omphalocele, and (ii) the day of Pdgfra deletion influenced the combinations, incidence and severities of these anomalies. Deletion of Pdgfra caused apoptosis of Pdgfra-expressing tissues, and developmental defects of their derivatives., Conclusion: Orofacial cleft, spina bifida and omphalocele are among the commonest skeletal and abdominal wall defects of newborns, but their genetic etiologies are largely unknown. The remarkable resemblance of our conditional Pdgfra knockout embryos to theses human congenital anomalies, suggesting that dysregulated PDGFRA expression could cause these anomalies in human. Future work should aim at defining (a) the regulatory elements for the expression of the human PDGFRA during embryonic development, and (b) if mutations / sequence variations of these regulatory elements cause these anomalies.

Both kanamycin A and kanamycin B, antibiotic components produced by Streptomyces kanamyceticus, have medical value. Two different pathways for kanamycin biosynthesis have been reported by two research groups. In this study, to obtain an optimal kanamycin A-producing strain and a kanamycin B-high-yield strain, we first examined the native kanamycin biosynthetic pathway in vivo. Based on the proposed parallel biosynthetic pathway, kanN disruption should lead to kanamycin A accumulation; however, the kanN-disruption strain produced neither kanamycin A nor kanamycin B. We then tested the function of kanJ and kanK. The main metabolite of the kanJ-disruption strain was identified as kanamycin B. These results clarified that kanamycin biosynthesis does not proceed through the parallel pathway and that synthesis of kanamycin A from kanamycin B is catalyzed by KanJ and KanK in S. kanamyceticus. As expected, the kanamycin B yield of the kanJ-disruption strain was 3268±255 μg/mL, 12-fold higher than that of the original strain. To improve the purity of kanamycin A and reduce the yield of kanamycin B in the fermentation broth, four different kanJ- and kanK-overexpressing strains were constructed through either homologous recombination or site-specific integration. The overexpressing strain containing three copies of kanJ and kanK in its genome exhibited the lowest kanamycin B yield (128±20 μg/mL), which was 54% lower than that of the original strain. Our experimental results demonstrate that kanamycin A is derived from KanJ-and-KanK-catalyzed conversion of kanamycin B in S. kanamyceticus. Moreover, based on the clarified biosynthetic pathway, we obtained a kanamycin B-high-yield strain and an optimized kanamycin A-producing strain with minimal byproduct.

We describe the population structure of a representative collection of 3,133 Mycobacterium tuberculosis isolates, collected within the framework of a national resistance survey from 2007 in China. Genotyping data indicate that the epidemic strains in China can be divided into seven major complexes, of which 92% belonged to the East Asian (mainly Beijing strains) or the Euro-American lineage. The epidemic Beijing strains in China are closely related to the Beijing B0/W148 strain earlier described in Russia and a large cluster of these strains has spread national wide. The density of Beijing strains is high in the whole of China (average 70%), but the highest prevalence was found North of the Yellow river. The Euro-American lineage consists of three sublineages (sublineage&#95;1, 2, and 3) and is more prevalent in the South. Beijing lineage showed the highest cluster rate of 48% and a significantly higher level of resistance to rifampicin (14%, p<0.001), ethambutol (9%, p = 0.001), and ofloxacin (5%, p = 0.011). Within the Euro-American Lineage, sublineage&#95;3 revealed the highest cluster rate (28%) and presented a significantly elevated level of resistance to streptomycin (44%, p<0.001). Our findings suggest that standardised treatment in this region may have contributed to the successful spread of certain strains: sublineage&#95;3 in the Euro-American lineage may have thrived when streptomycin was used without rifampicin for treatment, while later under DOTS based treatment, in which rifampicin plays a key role, Beijing lineage appears to be spreading.

To elucidate metabolism of ascorbic acid (AsA) in sweet cherry fruit (Prunus avium 'Hongdeng'), we quantified AsA concentration, cloned sequences involved in AsA metabolism and investigated their mRNA expression levels, and determined the activity levels of selected enzymes during fruit development and maturation. We found that AsA concentration was highest at the petal-fall period (0 days after anthesis) and decreased progressively during ripening, but with a slight increase at maturity. AsA did nevertheless continue to accumulate over time because of the increase in fruit fresh weight. Full-length cDNAs of 10 genes involved in the L-galactose pathway of AsA biosynthesis and 10 involved in recycling were obtained. Gene expression patterns of GDP-L-galactose phosphorylase (GGP2), L-galactono-1, 4-lactone dehydrogenase (GalLDH), ascorbate peroxidase (APX3), ascorbate oxidase (AO2), glutathione reductase (GR1), and dehydroascorbate reductase (DHAR1) were in accordance with the AsA concentration pattern during fruit development, indicating that genes involved in ascorbic acid biosynthesis, degradation, and recycling worked in concert to regulate ascorbic acid accumulation in sweet cherry fruit.

Studies have demonstrated that nucleotide-binding site-leucine-rich repeat (NBS-LRR) genes respond to pathogen attack in plants. Characterization of NBS-LRR genes in peanut is not well documented. The newly released whole genome sequences of Arachis duranensis and Arachis ipaënsis have allowed a global analysis of this important gene family in peanut to be conducted. In this study, we identified 393 (AdNBS) and 437 (AiNBS) NBS-LRR genes from A. duranensis and A. ipaënsis, respectively, using bioinformatics approaches. Full-length sequences of 278 AdNBS and 303 AiNBS were identified. Fifty-one orthologous, four AdNBS paralogous, and six AiNBS paralogous gene pairs were predicted. All paralogous gene pairs were located in the same chromosomes, indicating that tandem duplication was the most likely mechanism forming these paralogs. The paralogs mainly underwent purifying selection, but most LRR 8 domains underwent positive selection. More gene clusters were found in A. ipaënsis than in A. duranensis, possibly owing to tandem duplication events occurring more frequently in A. ipaënsis. The expression profile of NBS-LRR genes was different between A. duranensis and A. hypogaea after Aspergillus flavus infection. The up-regulated expression of NBS-LRR in A. duranensis was continuous, while these genes responded to the pathogen temporally in A. hypogaea., Competing Interests: The authors have declared that no competing interests exist.

To investigate the factors associated with sexually transmitted infection and Human Immunodeficiency Virus (STI-HIV) co-infection among men who have sex with men (MSM). A total of 357 HIV-infected participants (84 STI-HIV co-infection and 273 HIV infections only) were recruited from Jiangsu, China. Logistic regression analyses were used to estimate the related factors associated with STI-HIV co-infection. Marginal structural models were adopted to estimate the effect of transmission drug resistance (TDR) on STI-HIV co-infection. For all participants, logistic regression analyses revealed that those who diagnosed with HIV-1 for longer duration (≥1.8 years) were significantly associated with reduced STI-HIV co-infection risk (OR = 0.55, 95%CI: 0.32-0.96, P = 0.036). In further stratification analysis by antiretroviral therapy (ART), individuals with longer duration showed consistent significant associations with STI-HIV co-infection risk (OR = 0.46, 95%CI: 0.26-0.83, P = 0.010) among MSM with ART-naïve status. In addition, significant reduced risk for STI-HIV co-infection (OR = 0.98, 95%CI: 0.96-0.99, P = 0.010) were observed in younger (under the average age of 31.03) MSM of the same group. Interestingly, we also found TDR was significantly associated with an increased risk of STI-HIV co-infection risk (OR = 3.84, 95%CI: 1.05-14.03, P = 0.042) in ART-naïve group. Our study highlights a pattern of STI-HIV co-infection among MSM in China and indicates that targeted interventions aimed at encouraging TDR monitoring in MSM with early HIV infection are warranted., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the performance of the Sensitire MYCOTB MIC Plate (MYCOTB) which could measure the twelve anti-tuberculosis drugs susceptibility on one 96-wells plate., Methods: A total of 140 MDR-TB strains and 60 non-MDR strains were sub-cultured and 193 strains were finally tested for drug resistance using MYCOTB and agar proportion method (APM) and another 7 strains failed of subculture. The drugs included ofloxacin (Ofx), moxifloxacin (Mfx), rifampin (RFP), amikacin (Am), rifabutin (Rfb), para-aminosalicylic acid (PAS), ethionamide (Eth), isoniazid (INH), kanamycin (Km), ethambutol (EMB), streptomycin (Sm), and cycloserine(Cs). The categorical agreement, conditional agreement, sensitivity and specificity of MYCOTB were assessed in comparison with APM. For strains with inconsistent results between MYCOTB and APM, the drug resistance related gene fragments were amplified and sequenced: gyrA for Ofx and Mfx; rpoB for RFP and Rfb; embB for EMB; rpsl for Sm; katG and the promoter region of inhA for INH, ethA and the promoter region of inhA for Eth. The sequence results were compared with results of MYCOTB and APM to analyze the consistency between sequence results and MYCOTB or APM., Results: The categorical agreement between two methods for each drug ranged from 88.6% to 100%. It was the lowest for INH (88.6%). The sensitivity and specificity of MYCOTB ranged from 71.4% to 100% and 84.3% to 100%, respectively. The sensitivity was lowest for Cs(71.4%), EMB at 10μg/ml (80.0%) and INH at 10.0μg/ml (84.6%). The specificity was lowest for Rfb (84.3%). Overall discordance between the two phenotypic methods was observed for 96 strains, of which 63 (65.6%) were found susceptible with APM and resistant with MYCOTB and the remaining 33(34.4%) strains were resistant by APM and susceptible with MYCOTB. 34/52 (65.4%) sequenced APM susceptible and MYCOTB resistant(APM-S/MYCOTB-R) strains had mutations or insertions in the amplified regions. 20/30 (66.7%) sequenced APM resistant and MYCOTB susceptible strains had mutations in the sequenced genes. MICs of twenty-nine of these thirty isolates were equal to or within 1 doubling dilution of the critical concentration., Conclusion: MYCOTB had good performance for most of tested drugs and could be used as an alternative to the more labor demanding and longer turnaround time solid culture based DST method for detection of drug susceptibility in China., Competing Interests: The authors have declared that no competing interests exist.

MiRNAs function in post-transcriptional regulation of gene expression and play very important roles in plant development. Lonicera japonica is one of the important medicinal plants in China. However, few studies on the discovery of conserved and novel miRNAs from L. japonica were reported. In this study, we employed deep sequencing technology to identify miRNAs in leaf and flower tissues of L. japonica. A total of 22.97 million clean reads from flower and leaf tissues were obtained, which generated 146 conserved miRNAs distributed in 20 families and 110 novel miRNAs. Accordingly, 72 differentially expressed miRNAs (P≤0.001) between leaves and flowers and their potential target genes were identified and validated. The qRT-PCR validation showed that majority of the differentially expressed miRNAs showed significant tissue-specific expression in L. japonica. Furthermore, the miRNA-mRNA and mRNA-mRNA regulatory networks were constructed using Cytoscape software. Taken together, this study identified a large number of miRNAs and target genes in L. japonica, which not only provides the first global miRNA expression profiles, but also sheds light on functional genomics research on L. japonica in the future., Competing Interests: The authors have declared that no competing interests exist.

The benchmark dose (BMD) method has been increasingly used to assess the health risks of cadmium (Cd) in epidemiological studies. The aim of our study was to estimate the threshold levels of urinary Cd (UCd) using the BMD method in a general population of Jiangshan City, Zhejiang Province of China. In our study, a total of 934 people (469 men, 465 women) were recruited and morning urine samples were collected from all the participants. Levels of Cd, creatinine, and renal dysfunction indicators such as retinol binding protein (RBP), β2-microglobulin (β2-MG), and N-acetyl-b-glucosaminidase (NAG) in urine were detected for analysis of BMD and BMD low (BMDL) of UCd. RBP, β2-MG, and NAG in urine all correlated significantly (P < 0.001) with UCd except of age (P = 0.767). When the benchmark response (BMR) was 5%, the BMD/BMDL of UCd for RBP, β2-MG, and NAG was 1.69/ 0.89, 1.24/0.62, 0.85/0.49 μg/g Cr in men and 1.70/0.76, 1.35/0.64, 1.36/0.65 μg/g Cr in women, respectively. If the BMR was set at 10%, the BMD/BMDL of UCd for RBP, β2-MG, and NAG was 2.44/1.59, 2.09/1.30, 1.80/1.04 μg/g Cr in men and 2.43/1.53, 2.10/1.34, 2.31/1.37 μg/g Cr in women, respectively. Our results provided evidence for Cd-induced tubular effects in cadmium non-polluted areas in China. Both β2-MG and NAG were more sensitive than RBP in response to Cd exposure. But β2-MG was the most sensitive indicator in women, and NAG was the most sensitive one in men.

In this study we first sought to determine whether RNA-binding protein with multiple splicing (RBPMS) can serve as a specific marker for cat retina ganglion cells (RGCs) using retrograde labeling and immunohistochemistry staining. RBPM was then used as an RGC marker to study RGC survival after optic nerve crush (ONC) and alpha-lipoic acid (ALA) treatment in cats. ALA treatment yielded a peak density of RBPMS-alpha cells within the peak isodensity zone (>60/mm2) which did not differ from ONC retinas. The area within the zone was significantly enlarged (control: 2.3%, ONC: 0.06%, ONC+ALA: 0.1%). As for the 10-21/mm2 zone, ALA treatment resulted in a significant increase in area (control: 34.5%, ONC: 12.1%, ONC+ALA: 35.9%). ALA can alleviate crush-induced RGC injury.

The small white butterfly Pieris rapae is one of the most destructive pests of Brassicaceae. Yet little is understood about its genes involved in development. To facilitate research on P. rapae, we sequenced the transcriptome of P. rapae during six developmental stages, including the egg, three larval stages, the pupa, and the adult. In total, 240 million high-quality reads were obtained. De novo assembly generated 96,069 unigenes with an average length of 1353 nt. Of these, 31,629 unigenes had homologs as determined by a blastx search against the NR database with a cut-off e-value of 10-5. Clusters of Orthologous Groups of proteins (COG), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to functionally annotate those genes. Then, 849 genes involved in seven canonical development signaling pathway were identified, including dozens of key genes such as Hippo, Notch, and JAK2. A total of 21,883 differentially expressed (cut-off of 2-fold) unigenes were detected across the developmental stages, most of which were found between the egg and first larval stages. Interestingly, only 34 differentially expressed unigenes, most of which are cuticle protein related genes, were detected with a cut-off of 210-fold. Furthermore, we identified 32 heat shock protein (Hsp) genes that were expressed with complete open reading frames. Based on phylogenetic trees of the Hsp genes, we found that Hsp genes with close evolutionary relationships had similar expression pattern. Additionally, partial pattern recognition receptors genes were found to be developmental regulated. This study provides comprehensive sequence resources for P. rapae and numerous differential expressed genes, and these findings will lay the foundation for future functional genomics studies on this species.

The stress-induced epimutations could be inherited over generations and play important roles in plant adaption to stressful environments. Upland rice has been domesticated in water-limited environments for thousands of years and accumulated drought-induced epimutations of DNA methylation, making it epigenetically differentiated from lowland rice. To study the epigenetic differentiation between upland and lowland rice ecotypes on their drought-resistances, the epigenetic variation was investigated in 180 rice landraces under both normal and osmotic conditions via methylation-sensitive amplified polymorphism (MSAP) technique. Great alterations (52.9~54.3% of total individual-locus combinations) of DNA methylation are recorded when rice encountering the osmotic stress. Although the general level of epigenetic differentiation was very low, considerable level of ΦST (0.134~0.187) was detected on the highly divergent epiloci (HDE). The HDE detected in normal condition tended to stay at low levels in upland rice, particularly the ones de-methylated in responses to osmotic stress. Three out of four selected HDE genes differentially expressed between upland and lowland rice under normal or stressed conditions. Moreover, once a gene at HDE was up-/down-regulated in responses to the osmotic stress, its expression under the normal condition was higher/lower in upland rice. This result suggested expressions of genes at the HDE in upland rice might be more adaptive to the osmotic stress. The epigenetic divergence and its influence on the gene expression should contribute to the higher drought-resistance in upland rice as it is domesticated in the water-limited environment.

Human FAM76B (hFAM76B) is a 39 kDa protein that contains homopolymeric histidine tracts, a targeting signal for nuclear speckles. FAM76B is highly conserved among different species, suggesting that it may play an important physiological role in normal cellular functions. However, a lack of appropriate tools has hampered study of this potentially important protein. To facilitate research into the biological function(s) of FAM76B, murine monoclonal antibodies (MAbs) against hFAM76B were generated by using purified, prokaryotically expressed hFAM76B protein. Six strains of MAbs specific for hFAM76B were obtained and characterized. The specificity of MAbs was validated by using FAM76B-/- HEK 293 cell line. Double immunofluorescence followed by laser confocal microscopy confirmed the nuclear speckle localization of hFAM76B, and the specific domains recognized by different MAbs were further elucidated by Western blot. Due to the high conservation of protein sequences between mouse and human FAM76B, MAbs against hFAM76B were shown to react with mouse FAM76B (mFAM76B) specifically. Lastly, FAM76B was found to be expressed in the normal tissues of most human organs, though to different extents. The MAbs produced in this study should provide a useful tool for investigating the biological function(s) of FAM76B.

This retrospective study was designed to investigate the correlation between a novel immunosubtyping method for hepatocellular carcinoma (HCC) and biological behavior of tumor cells. A series of 346 patients, who received hepatectomy at two surgical centers from January 2007 to October 2010, were enrolled in this study. The expressions of cytokeratin 19 (CK19), glypican 3 (GPC3), and CD34 were detected by immunohistochemical staining. The clinical stage was assessed using the sixth edition tumor-node-metastasis (TNM) system (UICC/AJCC, 2010).Vascular invasion comprised both microscopic and macroscopic invasion. The tumor size, lymph node involvement, and metastasis were determined by pathological as well as imaging studies. Recurrence was defined as the appearance of new lesions with radiological features typical of HCC, seen by at least two imaging methods. Survival curves for the patients were plotted using the Kaplan-Meier method, and differences between the curves were assessed using the log-rank test. Significant differences in morphology, histological grading, and TNM staging were observed between groups. Based on the immunohistochemical staining, the enrolled cases were divided into CK19+/GPC3+, CK19-/GPC3+ and CK19-/GPC3- three subtypes. CK19+/GPC3+ HCC has the highest risk of multifocality, microvascular invasion, regional lymph node involvement, and distant metastasis, followed by CK19-/GPC3+ HCC, then CK19-/GPC3-HCC. CK19+/GPC3+ HCC has the shortest recurrence time compared to other immunophenotype HCCs. CK19 and GPC3 expression profiling is an independent prognostic indicator in patients with HCC, and a larger sample size is needed to further investigate the effect of this immunosubtyping model in stratifying the outcome of HCC patients.

Polydactyly is one of the most common hereditary congenital limb malformations in chickens and other vertebrates. The zone of polarizing activity regulatory sequence (ZRS) is critical for the development of polydactyly. The causative mutation of polydactyly in the Silkie chicken has been mapped to the ZRS; however, the causative mutations of other chicken breeds are yet to be established. To understand whether the same mutation decides the polydactyly phenotype in other chicken breeds, we detected the single-nucleotide polymorphism in 26 different chicken breeds, specifically, 24 Chinese indigenous breeds and 2 European breeds. The mutation was found to have fully penetrated chickens with polydactyly in China, indicating that it is causative for polydactyly in Chinese indigenous chickens. In comparison, the mutation showed no association with polydactyly in Houdan chickens, which originate from France, Europe. Based on the different morphology of polydactyly in Chinese and European breeds, we assumed that the trait might be attributable to different genetic foundations. Therefore, we subsequently performed genome-wide association analysis (GWAS) to locate the region associated with polydactyly. As a result, a ~0.39 Mb genomic region on GGA2p was identified. The region contains six candidate genes, with the causative mutation found in Chinese indigenous breeds also being located in this region. Our results demonstrate that polydactyly in chickens from China and Europe is caused by two independent mutation events that are closely located in the chicken genome.

The high degree of intra-tumor heterogeneity has meant that it is important to develop sensitive and selective assays to detect low-abundance KRAS mutations in metastatic colorectal carcinoma (mCRC) patients. As a major potential source of tumor DNA in the aforementioned genotyping assays, it was necessary to conduct an analysis on both the quality and quantity of DNA extracted from formalin-fixed paraffin-embedded (FFPE). Therefore, four commercial FFPE DNA extraction kits were initially compared with respect to their ability to facilitate extraction of amplifiable DNA. The results showed that TrimGen kits showed the greatest performance in relation to the quality and quantity of extracted FFPE DNA solutions. Using DNA extracted by TrimGen kits as a template for tumor genotyping, a real-time wild-type blocking PCR (WTB-PCR) assay was subsequently developed to detect the aforementioned KRAS mutations in mCRC patients. The results showed that WTB-PCR facilitated the detection of mutated alleles at a ratio of 1:10,000 (i.e. 0.01%) wild-type alleles. When the assay was subsequently used to test 49 mCRC patients, the results showed that the mutation detection levels of the WTB-PCR assay (61.8%; 30/49) were significantly higher than that of traditional PCR (38.8%; 19/49). Following the use of the real-time WTB-PCR assay, the ΔCq method was used to quantitatively analyze the mutation levels associated with KRAS in each FFPE sample. The results showed that the mutant levels ranged from 53.74 to 0.12% in the patients analyzed. In conclusion, the current real-time WTB-PCR is a rapid, simple, and low-cost method that permits the detection of trace amounts of the mutated KRAS gene.