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Background: This study aimed to investigate the prognostic value of the geriatric nutritional risk index (GNRI) in patients with non-metastatic clear cell renal cell carcinoma (ccRCC) who underwent nephrectomy., Methods: Patients with non-metastatic ccRCC who underwent nephrectomy between 2013 and 2021 were analyzed retrospectively. The GNRI was calculated within one week before surgery. The optimal cut-off value of GNRI was determined using X-tile software, and the patients were divided into a low GNRI group and a high GNRI group. The Kaplan-Meier method was used to compare the overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) between the two groups. Univariate and multivariate Cox proportional hazard models were used to determine prognostic factors. In addition, propensity score matching (PSM) was performed with a matching ratio of 1:3 to minimize the influence of confounding factors. Variables entered into the PSM model were as follows: sex, age, history of hypertension, history of diabetes, smoking history, BMI, tumor sidedness, pT stage, Fuhrman grade, surgical method, surgical approach, and tumor size., Results: A total of 645 patients were included in the final analysis, with a median follow-up period of 37 months (range: 1-112 months). The optimal cut-off value of GNRI was 98, based on which patients were divided into two groups: a low GNRI group (≤ 98) and a high GNRI group (> 98). Kaplan-Meier analysis showed that OS (P < 0.001), CSS (P < 0.001) and RFS (P < 0.001) in the low GNRI group were significantly worse than those in the high GNRI group. Univariate and multivariate Cox analysis showed that GNRI was an independent prognostic factor of OS, CSS and RFS. Even after PSM, OS (P < 0.05), CSS (P < 0.05) and RFS (P < 0.05) in the low GNRI group were still worse than those in the high GNRI group. In addition, we observed that a low GNRI was associated with poor clinical outcomes in elderly subgroup (> 65) and young subgroup (≤ 65), as well as in patients with early (pT1-T2) and low-grade (Fuhrman I-II) ccRCC., Conclusion: As a simple and practical tool for nutrition screening, the preoperative GNRI can be used as an independent prognostic indicator for postoperative patients with non-metastatic ccRCC. However, larger prospective studies are necessary to validate these findings., (© 2024. The Author(s).)

Background: Infectious diseases persistently pose global threats, and it is imperative to accelerate the professionalization of public health workforce. This study aimed to develop and validate the infectious disease control competency scale (IDCCS) for public health professionals to fill a theoretical gap and elevate practical capabilities by informing public health professionals' development goals., Methods: The initial item pool was generated through a literature review, and categorized into three dimensions (knowledge, practical skills, and leadership) based on the competency iceberg model and public health leadership framework. A two-round Delphi process was conducted to determine indicators within the scale. A pilot survey was utilized for item analysis and exploratory factor analysis (EFA). A formal survey was employed for confirmatory factor analysis (CFA). The weight value of each indicator was calculated using the analytic hierarchy process., Results: An initial scale with three primary items, 14 secondary items, and 81 tertiary items was generated. Twenty experts participated in the two rounds of the Delphi process. Authority coefficients exceeded 0.9 in both rounds. Kendall's W was 0.29 and 0.19, respectively (both P < 0.001). Item analysis presented a Cronbach's Alpha of 0.98, with corrected item-total correlation coefficients ranging from 0.33 to 0.78. EFA demonstrated that cumulative variance explanations for the four primary dimensions (knowledge, practical skills, leadership, and personal quality) were 77.463%, 73.976%, 81.174%, and 68.654%, respectively. CFA indicated that all composite reliability values and average variance extracted surpassed 0.8 and 0.5, respectively. The standardized factor loadings of the items ranged from 0.630 to 0.977. Among the seven model fit indices, each of the four dimensions satisfied at least five criteria. A final three-level scale comprising four primary items, 14 secondary items, and 64 tertiary items was constructed. The weight values for the four primary items were 0.4064, 0.2878, 0.2082, and 0.0981, respectively., Conclusions: The IDCCS was established to evaluate the competencies of knowledge, practical skills, leadership, and personal quality for public health professionals in infectious disease control. This scale demonstrates good reliability and validity, and can be used for performance evaluation, recruitment processes, curriculum development, and individual self-assessment., (© 2024. The Author(s).)

Background: Proliferative hepatocellular carcinomas (HCCs) is a class of aggressive tumors with poor prognosis. We aimed to construct a computed tomography (CT)-based radiomics nomogram to predict proliferative HCC, stratify clinical outcomes and explore the tumor microenvironment., Methods: Patients with pathologically diagnosed HCC following a hepatectomy were retrospectively collected from two medical centers. A CT-based radiomics nomogram incorporating radiomics model and clinicoradiological features to predict proliferative HCC was constructed using the training cohort (n = 184), and validated using an internal test cohort (n = 80) and an external test cohort (n = 89). The predictive performance of the nomogram for clinical outcomes was evaluated for HCC patients who underwent surgery (n = 201) or received transarterial chemoembolization (TACE, n = 104). RNA sequencing data and histological tissue slides from The Cancer Imaging Archive database were used to perform transcriptomics and pathomics analysis., Results: The areas under the receiver operating characteristic curve of the radiomics nomogram to predict proliferative HCC were 0.84, 0.87, and 0.85 in the training, internal test, and external test cohorts, respectively. The radiomics nomogram could stratify early recurrence-free survivals in the surgery outcome cohort (hazard ratio [HR] = 2.25; P < 0.001) and progression-free survivals in the TACE outcome cohort (HR = 2.21; P = 0.03). Transcriptomics and pathomics analysis indicated that the radiomics nomogram was associated with carbon metabolism, immune cells infiltration, TP53 mutation, and heterogeneity of tumor cells., Conclusion: The CT-based radiomics nomogram could predict proliferative HCC, stratify clinical outcomes, and measure a pro-tumor microenvironment., (© 2024. The Author(s).)

Background: Telemedicine is beneficial for improving treatment efficiency and reducing medical expenses of cancer patients. This study focuses on cancer patients participating in teleconsultations through a regional telemedicine platform in China, analyzes the consultation process, and provides references for the clinical application of telemedicine., Methods: We collected information on teleconsultations of cancer patients conducted from 2015 to 2022 through the regional telemedicine platform. Utilizing SPSS 23.0 software, we conducted descriptive analysis to summarize the distribution of patient gender, age, region, and disease types. The ordinal logistic regression analysis was adopted to analyze the factors influencing the waiting time and consultation duration for teleconsultations., Results: From 2015 to 2022, a total of 23,060 teleconsultations were conducted for cancer patients via regional telemedicine platform, with an average growth rate of 11.09%. The main types of consultations were for lung cancer, liver cancer, and breast cancer, accounting for 18.14%, 10.49%, and 9.46% respectively. 57.05% of teleconsultations had a waiting time of less than 24 h, while patient age, consultation expert level, and disease type were the main factors influencing the waiting time. 50.06% of teleconsultations had a duration of more than 20 min, and the inviting hospital level and the title of invited consultant were the main factors influencing the consultation duration., Conclusions: In China, telemedicine has been widely employed in the clinical diagnosis and treatment of cancers, covering various types of oncological diseases. However, the waiting time for teleconsultations was generally more than 12 h, indicating the need to enhance consultation scheduling and allocate more expert resources to further optimize the efficiency of teleconsultations. Additionally, further exploration is required for remote health management of outpatients with cancers outside the hospital., (© 2024. The Author(s).)

Background: Indoor residual spraying (IRS) has been implemented to prevent malaria in Zambia for several decades, but its effectiveness has not been evaluated long term and in Vubwi District yet. This study aimed to assess the association between IRS and the malaria burden in Zambia and Vubwi District and to explore the factors associated with refusing IRS., Methods: A retrospective study was used to analyze the association between IRS and malaria incidence in Zambia in 2001-2020 and in Vubwi District in 2014-2020 by Spearman correlation analysis. A case-control study was used to explore the factors associated with IRS refusals by households in Vubwi District in 2021. A logistic regression model was performed to identify factors associated with IRS refusals., Results: The malaria incidence reached its peak (391/1000) in 2001 and dropped to the lowest (154/1000) in 2019. The annual percentage change in 2001-2003, 2003-2008, 2008-2014, 2014-2018 and 2018-2020 was - 6.54%, - 13.24%, 5.04%, - 10.28% and 18.61%, respectively. A significantly negative correlation between the percentage of population protected by the IRS against the total population in Zambia (coverage) and the average malaria incidence in the whole population was observed in 2005-2020 (r = - 0.685, P = 0.003) and 2005-2019 (r = - 0.818, P < 0.001). Among 264 participants (59 in the refuser group and 205 in the acceptor group), participants with specific occupations (self-employed: OR 0.089, 95% CI 0.022-0.364; gold panning: OR 0.113, 95% CI 0.022-0.574; housewives: OR 0.129, 95% CI 0.026-0.628 and farmers: OR 0.135, 95% CI 0.030-0.608 compared to employees) and no malaria case among household members (OR 0.167; 95% CI 0.071-0.394) had a lower risk of refusing IRS implementation, while those with a secondary education level (OR 3.690, 95% CI 1.245-10.989) had a higher risk of refusing IRS implementation compared to those who had never been to school., Conclusions: Increasing coverage with IRS was associated with decreasing incidence of malaria in Zambia, though this was not observed in Vubwi District, possibly because of the special geographical location of Vubwi District. Interpersonal communication and targeted health education should be implemented at full scale to ensure household awareness and gain community trust., (© 2024. The Author(s).)

Background: A promoter is a specific sequence in DNA that has transcriptional regulatory functions, playing a role in initiating gene expression. Identifying promoters and their strengths can provide valuable information related to human diseases. In recent years, computational methods have gained prominence as an effective means for identifying promoter, offering a more efficient alternative to labor-intensive biological approaches., Results: In this study, a two-stage integrated predictor called "msBERT-Promoter" is proposed for identifying promoters and predicting their strengths. The model incorporates multi-scale sequence information through a tokenization strategy and fine-tunes the DNABERT model. Soft voting is then used to fuse the multi-scale information, effectively addressing the issue of insufficient DNA sequence information extraction in traditional models. To the best of our knowledge, this is the first time an integrated approach has been used in the DNABERT model for promoter identification and strength prediction. Our model achieves accuracy rates of 96.2% for promoter identification and 79.8% for promoter strength prediction, significantly outperforming existing methods. Furthermore, through attention mechanism analysis, we demonstrate that our model can effectively combine local and global sequence information, enhancing its interpretability., Conclusions: msBERT-Promoter provides an effective tool that successfully captures sequence-related attributes of DNA promoters and can accurately identify promoters and predict their strengths. This work paves a new path for the application of artificial intelligence in traditional biology., (© 2024. The Author(s).)

Background: The 17-gene Genomic Prostate Score (GPS) test has been clinically employed to predict adverse prognosis in prostate cancer. In this meta-analysis, we aimed to evaluate the prognostic value of the 17-gene GPS in patients with prostate cancer., Methods: Potentially relevant studies were obtained by searching PubMed, Web of Science, Embase databases from their inception to December 1, 2023. Studies were considered eligible if they evaluated the association of the 17-gene GPS with distant metastases, biochemical recurrence, or prostate cancer-specific mortality (PCSM) in prostate cancer patients. To estimate the prognostic value, we pooled the adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the high versus low GPS group or per 20-unit increase in GPS., Results: Seven cohort studies that reported on 8 articles comprising 1,962 patients satisfied the eligibility criteria. Meta-analysis showed that per 20-unit increase in GPS was significantly associated with distant metastases (HR 2.99; 95% CI 1.97-4.53), biochemical recurrence (HR 2.18; 95% CI 1.64-2.89), and PCSM (HR 3.14; 95% CI 1.86-5.30). Moreover, patients with high GPS (> 40 points) had an increased risk of distant metastases (HR 5.22; 95% CI 3.72-7.31), biochemical recurrence (HR 4.41; 95% CI 2.29-8.49), and PCSM (HR 3.81; 95% CI 1.74-8.33) than those with low GPS (≤ 40 points)., Conclusions: A higher 17-gene GPS significantly predicts distant metastases, biochemical recurrence, and PCSM in men with clinically localized prostate cancer. However, large-scale multicenter prospective studies are necessary to further validate these findings., (© 2024. The Author(s).)

The elderly frequently present impaired blood-brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, the most abundant protein in the plasma, leaking through the disrupted BBB, contributes to the neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes to A1 phenotype to remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis through endoplasmic reticulum stress response pathway. Moreover, MSA-activated microglia triggered remarkable tau phosphorylation at multiple sites through NLRP3 inflammasome pathway. Intracerebroventricular injection of MSA into the brains of C57BL/6J mice to a similar concentration as in patient brains induced neuronal apoptosis, neuroinflammation, increased tau phosphorylation, and decreased the spatial learning and memory abilities, while Elovl1 knockdown significantly prevented the deleterious effect of MSA. Overall, our study here revealed that MSA induced tau phosphorylation and neuron apoptosis based on MSA-activated microglia and astrocytes, respectively, showing the critical roles of MSA in initiating the occurrence of tauopathies and cognitive decline, and providing potential therapeutic targets for MSA-induced neuropathology in multiple neurodegenerative disorders., (© 2024. The Author(s).)

Spike length (SL) is one of the most important agronomic traits affecting yield potential and stability in wheat. In this study, a major stable quantitative trait locus (QTL) for SL, i.e., qSl-2B, was detected in multiple environments in a recombinant inbred line (RIL) mapping population, KJ-RILs, derived from a cross between Kenong 9204 (KN9204) and Jing 411 (J411). The qSl-2B QTL was mapped to the 60.06-73.06 Mb region on chromosome 2B and could be identified in multiple mapping populations. An InDel molecular marker in the target region was developed based on a sequence analysis of the two parents. To further clarify the breeding use potential of qSl-2B, we analyzed its genetic effects and breeding selection effect using both the KJ-RIL population and a natural mapping population, which consisted of 316 breeding varieties/advanced lines. The results showed that the qSl-2B alleles from KN9204 showed inconsistent genetic effects on SL in the two mapping populations. Moreover, in the KJ-RILs population, the additive effects analysis of qSl-2B showed that additive effect was higher when both qSl-2D and qSl-5A harbor negative alleles under LN and HN. In China, a moderate selection utilization rate for qSl-2B was found in the Huanghuai winter wheat area and the selective utilization rate for qSl-2B continues to increase. The above findings provided a foundation for the genetic improvement of wheat SL in the future via molecular breeding strategies., (© 2024. The Author(s).)

Background: A consensus has not been reached on the value of prostate-specific antigen density (PSAD) as a predictor of biochemical recurrence of prostate cancer. This meta-analysis aimed to evaluate the association between PSAD and biochemical recurrence of prostate cancer after primary treatment., Methods: Two authors systematically searched PubMed, Web of Science, and Embase databases (up to August September 10, 2023) to identify studies that assessed the value of pretreatment PSAD in predicting biochemical recurrence after primary treatment (radical prostatectomy or radiotherapy) of prostate cancer. A random effect model was used to pool adjusted hazard ratios (HR) with 95% confidence intervals (CI) for biochemical recurrence., Results: Nine studies with 4963 patients were eligible for the meta-analysis. The reported prevalence of biochemical recurrence ranged from 4 to 55.1%. For patients with higher PSAD compared to those with low PSAD, the pooled HR of biochemical recurrence was 1.59 (95% CI 1.21-2.10). Subgroup analysis showed that the pooled HR of biochemical recurrence was 1.80 (95% CI 1.34-2.42) for patients who received radical prostatectomy, and 0.98 (95% CI 0.66-1.45) for patients who received radiotherapy., Conclusions: Elevated pretreatment PSAD may be an independent predictor for biochemical recurrence of prostate cancer after radical prostatectomy. Determining PSAD could potentially improve the prediction of biochemical recurrence in patients with prostate cancer., (© 2024. The Author(s).)

Background: Maize kernel colour is an important index for evaluating maize quality and value and mainly entails two natural pigments, carotenoids and anthocyanins. To analyse the genetic mechanism of maize kernel colour and mine single nucleotide polymorphisms (SNPs) related to kernel colour traits, an association panel including 244 superior maize inbred lines was used to measure and analyse the six traits related to kernel colour in two environments and was then combined with the about 3 million SNPs covering the whole maize genome in this study. Two models (Q + K, PCA + K) were used for genome-wide association analysis (GWAS) of kernel colour traits., Results: We identified 1029QTLs, and two SNPs contained in those QTLs were located in coding regions of Y1 and R1 respectively, two known genes that regulate kernel colour. Fourteen QTLs which contain 19 SNPs were within 200 kb interval of the genes involved in the regulation of kernel colour. 13 high-confidence SNPs repeatedly detected for specific traits, and AA genotypes of rs1&#95;40605594 and rs5&#95;2392770 were the most popular alleles appeared in inbred lines with higher levels. By searching the confident interval of the 13 high-confidence SNPs, a total of 95 candidate genes were identified., Conclusions: The genetic loci and candidate genes of maize kernel colour provided in this study will be useful for uncovering the genetic mechanism of maize kernel colour, gene cloning in the future. Furthermore, the identified elite alleles can be used to molecular marker-assisted selection of kernel colour traits., (© 2023. The Author(s).)

Background: Research on the association between telomere length (TL) and incident non-alcoholic fatty liver disease (NAFLD) is limited. This study examined this association and further assessed how TL contributes to the association of NAFLD with its known risk factors., Methods: Quantitative PCR (polymerase chain reaction) was employed to assess leucocyte telomere length. Polygenic risk score (PRS) for NAFLD, air pollution score, and lifestyle index were constructed. Cox proportional hazard models were conducted to estimate the hazard ratios (HRs) and 95% confidence intervals., Results: Among 467,848 participants in UK Biobank, we identified 4809 NAFLD cases over a median follow-up of 12.83 years. We found that long TL was associated with decreased risk of incident NAFLD, as each interquartile range increase in TL resulted in an HR of 0.93 (95% CI 0.89, 0.96). TL partly mediated the association between age and NAFLD (proportion mediated: 15.52%). When assessing the joint effects of TL and other risk factors, the highest risk of NAFLD was found in participants with low TL and old age, low TL and high air pollution score, low TL and unfavorable lifestyle, and low TL and high PRS, compared to each reference group. A positive addictive interaction was observed between high PRS and low TL, accounting for 14.57% (2.51%, 27.14%) of the risk of NAFLD in participants with low telomere length and high genetic susceptibility., Conclusions: Long telomere length was associated with decreased risk of NAFLD incidence. Telomere length played an important role in NAFLD., (© 2023. The Author(s).)

Background: Microcystic urothelial carcinoma (MUC) is a rare variant of urothelial carcinoma with histological appearances similar to begin lesions. Thus far, approximately 50 cases have been reported. Here, we investigated the clinicopathological features of MUC., Methods: Clinical data and paraffin-embedded tissue blocks were collected. Immunohistochemical staining and polymerase chain reaction-Sanger sequencing were performed to detect the phenotype and TERT mutation status of MUC, respectively., Results: The mean patient age was 58.8 ± 14.5 years, with a male predominance (8:2). The pathological stage was T1 in one case, T2 in three cases, T3 in four cases, and T4 in two cases. Tumor metastases or death occurred in all five patients who were followed up within 1-3 years. Histological analyses revealed microcystic, tubular, cribriform, and occasionally cord-like structures, which generally lacked interstitial reactions. The lumens were empty, contained eosinophilic secretion, or were filled with mucin. The microcysts/tubules/cribriform patterns were lined by flat, cuboid, signet ring, or columnar types of epithelia. The cuboid, signet ring, and columnar types represented "glandular metaplasia" or glandular differentiation of urothelial carcinoma. Immunohistochemistry analyses revealed distinct co-expression patterns involving the luminal markers FOXA1 and GATA3, as well as the basal markers CK5/6 and CD44. All 10 cases exhibited a luminal phenotype according to the GATA3+/CK14- criterion, whereas nine cases exhibited a luminal phenotype according to the FOXA1+/CK14- criterion. The telomerase reverse transcriptase-C228T mutation was detected in seven cases., Conclusions: MUC is a rare variant with a deceptively benign form of urothelial carcinoma, which is generally identified as a late-stage tumor with a poor prognosis. It exhibits distinct co-expression of luminal and basal markers, along with the TERT-C228T mutation., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Histological assessment of smooth muscle is a critical step particularly in staging malignant tumors in various internal organs including  the urinary bladder. Nonetheless, manual segmentation and classification of muscular tissues by pathologists is often challenging. Therefore, a fully automated and reliable smooth muscle image segmentation system is in high demand., Methods: To characterize muscle fibers in the urinary bladder, including muscularis mucosa (MM) and muscularis propria (MP), we assessed 277 histological images from surgical specimens, using two well-known deep learning (DL) model groups, one including VGG16, ResNet18, SqueezeNet, and MobileNetV2, considered as a patch-based approach, and the other including U-Net, MA-Net, DeepLabv3 + , and FPN, considered as a pixel-based approach. All the trained models in both the groups were evaluated at pixel-level for their performance., Results: For segmenting MP and non-MP (including MM) regions, MobileNetV2, in the patch-based approach and U-Net, in the pixel-based approach outperformed their peers in the groups with mean Jaccard Index equal to 0.74 and 0.79, and mean Dice co-efficient equal to 0.82 and 0.88, respectively. We also demonstrated the strengths and weaknesses of the models in terms of speed and prediction accuracy., Conclusions: This work not only creates a benchmark for future development of tools for the histological segmentation of smooth muscle but also provides an effective DL-based diagnostic system for accurate pathological staging of bladder cancer., (© 2023. The Author(s).)

Background: Efforts to precisely assess tumor-specific T-cell immune responses still face major challenges, and the potential molecular mechanisms mediating hepatocellular carcinoma (HCC) microenvironment imbalance after incomplete radiofrequency ablation (iRFA) are unclear. This study aimed to provide further insight into the integrated transcriptomic and proteogenomic landscape and identify a new target involved in HCC progression following iRFA., Methods: Peripheral blood and matched tissue samples were collected from 10 RFA-treated HCC patients. Multiplex immunostaining and flow cytometry were used to assess local and systemic immune responses. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were explored via transcriptomic and proteogenomic analyses. Proteinase-3 (PRTN3) was identified in these analyses. And then, the ability of PRTN3 to predict overall survival (OS) was assessed in 70 HCC patients with early recurrence after RFA. In vitro CCK-8, wound healing and transwell assays were conducted to observe interactions between Kupffer cells (KCs) and HCC cells induced by PRTN3. The protein levels of multiple oncogenic factors and signaling pathway components were detected by western blotting. A xenograft mouse model was built to observe the tumorigenic effect of PRTN3 overexpression on HCC., Results: Multiplex immunostaining revealed no immediate significant change in local immune cell counts in periablational tumor tissues after 30 min of iRFA. Flow cytometry showed significantly increased levels of CD4 + T cells, CD4 + CD8 + T cells, and CD4 + CD25 + CD127 - Tregs and significantly decreased the levels of CD16 + CD56 + natural killer cells on day 5 after cRFA (p < 0.05). Transcriptomics and proteomics revealed 389 DEGs and 20 DEPs. Pathway analysis showed that the DEP-DEGs were mainly enriched in the immunoinflammatory response, cancer progression and metabolic processes. Among the DEP-DEGs, PRTN3 was persistently upregulated and closely associated with the OS of patients with early recurrent HCC following RFA. PRTN3 expressed in KCs may affect the migration and invasion of heat stress-treated HCC cells. PRTN3 promotes tumor growth via multiple oncogenic factors and the PI3K/AKT and P38/ERK signaling pathways., Conclusions: This study provides a comprehensive overview of the immune response and transcriptomic and proteogenomic landscapes of the HCC milieu induced by iRFA, revealing that PRTN3 promotes HCC progression after iRFA., Trial Registration: ChiCTR2200055606, http://www.chictr.org.cn/showproj.aspx?proj=32588 ., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The pathogenic viruses transmitted by mosquitoes cause a variety of animal and human diseases and public health concerns. Virome surveillance is important for the discovery, and control of mosquito-borne pathogenic viruses, as well as early warning systems. Virome composition in mosquitoes is affected by mosquito species, food source, and geographic region. However, the complex associations of virome composition remain largely unknown., Results: Here, we profiled the high-depth RNA viromes of 15 species of field-caught adult mosquitoes, especially from Culex, Aedes, Anopheles, and Armigeres in Hainan Island from 2018 to 2020. We detected 57 known and 39 novel viruses belonging to 15 families. We established the associations of the RNA viruses with mosquito species and their foods, indicating the importance of feeding acquisition of RNA viruses in determining virome composition. A large fraction of RNA viruses were persistent in the same mosquito species across the 3 years and different locations, showing the species-specific stability of viromes in Hainan Island. In contrast, the virome compositions of single mosquito species in different geographic regions worldwide are visibly distinct. This is consistent with the differences in food sources of mosquitoes distributed broadly across continents., Conclusions: Thus, species-specific viromes in a relatively small area are limited by viral interspecific competition and food sources, whereas the viromes of mosquito species in large geographic regions may be governed by ecological interactions between mosquitoes and local environmental factors. Video Abstract., (© 2023. The Author(s).)

Objective: To explore the characteristics of renal artery variation in patients with renal cell carcinoma and to evaluate the predicting value of accessory renal artery in the pathological grading of renal cell carcinoma., Methods: The clinicopathological data of patients with clear cell renal cell carcinoma diagnosed in the Department of Urology of the First Hospital of Shanxi Medical University from September 2019 to March 2023 were retrospectively analyzed. All patients underwent visual three-dimensional model reconstruction from computed tomography images. All kidneys were divided into two groups: the affected kidney and the healthy kidney, and the incidence of renal artery variation in the two groups was analyzed. Then, according to the existence of accessory renal artery in the affected kidney, the patients were divided into two groups, and the relationship between accessory renal artery and clinicopathological features of patients with clear cell renal cell carcinoma was analyzed. Finally, univariate and multivariate logistic regression analyses were performed to determine the predictors of Fuhrman grading of clear cell renal cell carcinoma, and the predictive ability of the model was evaluated by the receiver operating characteristic curve., Results: The incidence of renal artery variation and accessory renal artery in the affected kidney was significantly higher than them in the healthy kidney. The patients with accessory renal artery in the affected kidney had larger tumor maximum diameter, higher Fuhrman grade and more exophytic growth. The presence of accessory renal artery on the affected kidney and the maximum diameter of tumor are independent predictors of high-grade renal cell carcinoma. The receiver operating characteristic curve suggests that the model has a good predictive ability., Conclusion: The existence of accessory renal artery on the affected kidney may be related to the occurrence and development of clear cell renal cell carcinoma, and can better predict Fuhrman grade of clear cell renal cell carcinoma. The finding provides a reference for the future diagnostic evaluation of RCC, and provides a new direction for the study of the pathogenesis of RCC., (© 2023. The Author(s).)

Background: Little is known about the association between the preoperative low-density lipoprotein cholesterol (LDL-C) level and prognosis in patients with renal cell carcinoma (RCC) after nephrectomy, and its prognostic value needs to be elucidated., Methods: The clinical and follow-up data of 737 RCC patients who underwent nephrectomy were retrospectively analyzed. The optimal cut-off LDL-C level was determined using X-tile, and then patients were divided into low and high LDL-C groups. The association between LDL-C levels and survival of RCC patients was assessed using the Kaplan-Meier method and Cox regression analysis., Results: The optimal cut-off LDL-C level was 1.93 mmol/L, and patients were divided into the low (≤ 1.93 mmol/L) and high LDL-C (> 1.93 mmol/L) groups. The Kaplan-Meier analysis showed that patients in the low LDL-C group had significantly shorter overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) than those in the high LDL-C group (P = 0.001, P = 0.001, and P = 0.003, respectively). The COX univariate analysis showed that the preoperative LDL-C level was closely associated with OS, CSS, and RFS in RCC patients (P = 0.002, P = 0.003, and P = 0.005, respectively). The multivariate analysis showed that the preoperative LDL-C level was an independent factor for predicting survival (OS, CSS and RFS) in RCC patients after nephrectomy. The low preoperative LDL-C levels predicted worse OS (hazard ratio [HR]: 2.337; 95% confidence interval [CI]: 1.192-4.581; P = 0.013), CSS (HR: 3.347; 95% CI: 1.515-7.392; P = 0.003), and RFS (HR: 2.207; 95% CI: 1.178-4.132; P = 0.013)., Conclusions: The preoperative LDL-C level is an independent factor for the prognosis of RCC patients after nephrectomy, and low preoperative LDL-C levels predict worse survival (OS, CSS, and RFS)., (© 2023. The Author(s).)

Background: The objective of this study was to reveal the flavonoid biosynthesis pathway in white (Z6), red (Z27) and black (HC4) seeds of the sweet sorghum (Sorghum bicolor) using metabolomics and transcriptomics, to identify different flavonoid metabolites, and to analyze the differentially expressed genes involved in flavonoid biosynthesis., Results: We analyzed the metabolomics and transcriptomics data of sweet sorghum seeds. Six hundred and fifty-one metabolites including 171 flavonoids were identified in three samples. Integrated analysis of transcriptomics and metabolomics showed that 8 chalcone synthase genes (gene19114, gene19115, gene19116, gene19117, gene19118, gene19120, gene19122 and gene19123) involved in flavonoid biosynthesis, were identified and play central role in change of color. Six flavanone including homoeriodictyol, naringin, prunin, naringenin, hesperetin and pinocembrin were main reason for the color difference., Conclusions: Our results provide valuable information on the flavonoid metabolites and the candidate genes involved in the flavonoid biosynthesis pathway in sweet sorghum seeds., (© 2022. The Author(s).)

Background: Indoor residual spraying (IRS) is one of the key interventions recommended by World Health Organization in preventing malaria infection. We aimed to conduct a systematic review and meta-analysis of global studies about the impact of IRS on malaria control., Method: We searched PubMed, Web of Science, Embase, and Scopus for relevant studies published from database establishment to 31 December 2021. Random-effects models were used to perform meta-analysis and subgroup analysis to pool the odds ratio (OR) and 95% confidence interval (CI). Meta-regression was used to investigate potential factors of heterogeneity across studies., Results: Thirty-eight articles including 81 reports and 1,174,970 individuals were included in the meta-analysis. IRS was associated with lower rates of malaria infection (OR = 0.35, 95% CI: 0.27-0.44). The significantly higher effectiveness was observed in IRS coverage ≥ 80% than in IRS coverage < 80%. Pyrethroids was identified to show the greatest performance in malaria control. In addition, higher effectiveness was associated with a lower gross domestic product as well as a higher coverage of IRS and bed net utilization., Conclusions: IRS could induce a positive effect on malaria infection globally. The high IRS coverage and the use of pyrethroids are key measures to reduce malaria infection. More efforts should focus on increasing IRS coverage, developing more effective new insecticides against malaria, and using multiple interventions comprehensively to achieve malaria control goals., (© 2022. The Author(s).)

Engineered probiotics are a kind of new microorganisms produced by modifying original probiotics through gene editing. With the continuous development of tools and technology progresses, engineering renovation of probiotics are becoming more diverse and more feasible. In the past few years there have been some advances in the development of engineered probiotics that will benefit humankind. This review briefly introduces the theoretical basis of gene editing technology and focuses on some recent engineered probiotics researches, including inflammatory bowel disease, bacterial infection, tumor and metabolic diseases. It is hoped that it can provide help for the further development of genetically modified microorganisms, stimulate the potential of engineered probiotics to treat intractable diseases, and provide new ideas for the diagnosis of some diseases or some industrial production., (© 2022. The Author(s).)

Objective: We sought to determine the association between mental stress-induced myocardial ischaemia (MSIMI) and quality of life (QoL) in patients with coronary artery disease (CAD) after coronary revascularization., Methods: This cohort study involved patients with high-risk MSIMI who received coronary revascularization between Dec 2018 and Dec 2019. Patients who screened positive for depression/anxiety were enrolled in this study. Mental stress was induced by the Stroop Colour and Word Test 1 month after coronary revascularization. All participants underwent single photon emission computed tomography (SPECT) scans at rest and under mental stress. MSIMI was defined as the presence of four abnormal SPECT phenomena. QoL was assessed using the Seattle Angina Questionnaire (SAQ) prior to treatment and 1 month after coronary revascularization., Results: Of the 1845 consecutive patients who received coronary revascularization, 590 (31.9%) had depression/anxiety, and 205 agreed to accept the mental stress test. During the average observation period of 33 days, 105 (51.2%) patients exhibited MSIMI. All SAQ subscales showed significant improvement, except for QoL, in the MSIMI group. The QoL score was lower (- 0.2 ± 32.7 vs. 13.1 ± 29.9, P = 0.005), and the proportion of deterioration in QoL was higher (50.5% vs. 31.9%, P = 0.010) in the MSIMI group than in the non-MSIMI group. Those with a deterioration in QoL had approximately twice the rate of MSIMI than those with an improvement in QoL (unadjusted OR: 2.019, 95% CI 1.122-3.634, P = 0.026; adjusted OR: 1.968, 95% CI 1.083-3.578, P = 0.017)., Conclusion: Among patients with CAD who received coronary revascularization and had depression/anxiety, deterioration in QoL increased the likelihood of MSIMI. Hence, our results indicate that deterioration in QoL is a predictor of MSIMI. Trail Registration ChiCTR2200055792, retrospectively registered, 2022.1.20, www.medresman.org.cn., (© 2022. The Author(s).)

Background: Small auxin-upregulated RNAs (SAURs) gene family plays important roles in plant growth, development, and stress responses. However, the function of few SAUR genes is known in the peanut (Arachis hypogaea L.), one of the world's major food legume crops. This study aimed to perform a comprehensive identification of the SAUR gene family from the peanut genome., Results: The genome-wide analysis revealed that a total of 162 SAUR genes were identified in the peanut genome. The phylogenetic analysis indicated that the SAUR proteins were classified into eight subfamilies. The SAUR gene family experienced a remarkable expansion after tetraploidization, which contributed to the tandem duplication events first occurring in subgenome A and then segmental duplication events occurring between A and B subgenomes. The expression profiles based on transcriptomic data showed that SAUR genes were dominantly expressed in the leaves, pistils, perianth, and peg tips, and were widely involved in tolerance against abiotic stresses. A total of 18 AhSAUR genes selected from different subfamilies randomly presented 4 major expression patterns according to their expression characteristics in response to indole-3-acetic acid. The members from the same subfamily showed a similar expression pattern. Furthermore, the functional analysis revealed that AhSAUR3 played a negative role in response to drought tolerance., Conclusions: This study provided insights into the evolution and function of the SAUR gene family and may serve as a resource for further functional research on AhSAUR genes., (© 2022. The Author(s).)

Background: Hand-foot-mouth disease (HFMD) is a global public health issues, especially in China. It has threat the health of children under 5 years old. The early recognition of high-risk districts and understanding of epidemic characteristics can facilitate health sectors to prevent the occurrence of HFMD effectively., Methods: Descriptive analysis was used to summarize epidemic characteristics, and the spatial autocorrelation analysis and space-time scan analysis were utilized to explore distribution pattern of HFMD and identify hot spots with statistical significance. The result was presented in ArcMap., Results: A total of 52,095 HFMD cases were collected in Zibo city from 1 Jan 2010 to 31 Dec 2019. The annual average incidence was 129.72/100,000. The distribution of HFMD was a unimodal trend, with peak from April to September. The most susceptible age group was children under 5 years old (92.46%), and the male-to-female ratio is 1.60: 1. The main clusters were identified in Zhangdian District from 12 April 2010 to 18 September 2012. Spatial autocorrelation analysis showed that the global spatial correlation in Zibo were no statistical significance, except in 2012, 2014, 2015, 2016 and 2018. Cold spots were gathered in Boshan county and Linzi district, while hot spots only in Zhangdian District in 2018, but other years were no significance., Conclusion: Hot spots mainly concentrated in the central and surrounding city of Zibo city. We suggest that imminent public health planning and resource allocation should be focused within those areas., (© 2021. The Author(s).)

Background: The mammalian target of rapamycin protein (mTOR) signaling pathway is involved in the pathogenesis of schizophrenia and the mechanism of extrapyramidal adverse reactions to antipsychotic drugs, which might be mediated by an mTOR-dependent autophagy impairment. This study aimed to examine the expression of mTOR pathway genes in patients with schizophrenia treated with olanzapine, which is considered an mTOR inhibitor and autophagy inducer., Methods: Thirty-two patients with acute schizophrenia who had been treated with olanzapine for four weeks (average dose 14.24 ± 4.35 mg/d) and 32 healthy volunteers were recruited. Before and after olanzapine treatment, the Positive and Negative Syndrome Scale (PANSS) was used to evaluate the symptoms of patients with schizophrenia, and the mRNA expression levels of mTOR pathway-related genes, including MTOR, RICTOR, RAPTOR, and DEPTOR, were detected in fasting venous blood samples from all subjects using real-time quantitative PCR., Results: The MTOR and RICTOR mRNA expression levels in patients with acute schizophrenia were significantly decreased compared with those of healthy controls and further significantly decreased after four weeks of olanzapine treatment. The DEPTOR mRNA expression levels in patients with acute schizophrenia were not significantly different from those of healthy controls but were significantly increased after treatment. The expression levels of the RAPTOR mRNA were not significantly different among the three groups. The pairwise correlations of MTOR, DEPTOR, RAPTOR, and RICTOR mRNA expression levels in patients with acute schizophrenia and healthy controls were significant. After olanzapine treatment, the correlations between the expression levels of the DEPTOR and MTOR mRNAs and between the DEPTOR and RICTOR mRNAs disappeared., Conclusions: Abnormalities in the mTOR pathway, especially DEPTOR and mTORC2, might play important roles in the autophagy mechanism underlying the pathophysiology of schizophrenia and effects of olanzapine treatment., (© 2021. The Author(s).)

Background: The prevalence of stress urinary incontinence (SUI) in adult female in Taiyuan and what are the related risk factors are not clear. The aim of this study was to provide a basis for exploring the prevention and treatment of SUI in adult female in Taiyuan., Methods: A voluntary online questionnaire was used to investigate adult female in the community and surrounding townships of Taiyuan. Most of the questionnaires refer to the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms, and adapt to the specific circumstances of the region. Data were analyzed using SPSS software (version 22.0)., Results: A total of 4004 eligible questionnaires were obtained. The prevalence of SUI in adult female in Taiyuan was 33.5%. Univariate analysis and multivariate logistic regression analysis showed that place of residence, smoking, body mass index, diet, number of deliveries, mode of delivery, dystocia, menopause, oral contraceptives, urinary tract infection, making the bladder empty faster by pushing down and holding urine were risk factors for adult female stress urinary incontinence in Taiyuan., Conclusion: The prevalence of SUI in adult female in Taiyuan was high, and based on risk factors identified in this survey, population-level intervention strategies should be developed for the prevention and treatment of adult female SUI in Taiyuan.

Background: Sleep disturbance and executive function impairment are common in patients with major depressive disorder (MDD), though the relationship between the two remains unclear. We investigated this association in first-episode, treatment-naïve patients with MDD., Methods: We analyzed data from 242 patients with MDD. We divided the patients into 2 groups based on sleep disturbance severity and compared the executive function odds ratios between the groups., Results: A total of 121 pairs of patients were matched (age 39.4 ± 10.1, 70.2% female). After propensity score matching, the odds ratios for cognitive impairment in patients with MDD and severe sleep disturbance were 1.922 (1.068-3.459, P = 0.029, q = 0.044) in executive functioning; 2.023 (1.211-3.379, P = 0.007, q = 0.021) in executive shifting., Conclusions: Sleep disturbance is associated with executive functioning impairment in first-episode, treatment-naïve patients with MDD. Severe sleep disturbance can be a marker and aid in recognizing executive function impairment in patients with first-episode treatment-naïve MDD. Severe sleep disturbance can be a potential modifiable factor to improve executive function in MDD, as well as an effective measurement to improve cognition for sleep symptom management that should be enforced at initial treatment of first-episode MDD. Further study is required to confirm our results., Trial Registration: ClinicalTrials.gov: NCT02023567 ; registration date: December 2013.

Background: Most transcription factors (TFs) compete with nucleosomes to gain access to their cognate binding sites. Recent studies have identified several TF-nucleosome interaction modes including end binding (EB), oriented binding, periodic binding, dyad binding, groove binding, and gyre spanning. However, there are substantial experimental challenges in measuring nucleosome binding modes for thousands of TFs in different species., Results: We present a computational prediction of the binding modes based on TF protein sequences. With a nested cross-validation procedure, our model outperforms several fine-tuned off-the-shelf machine learning (ML) methods in the multi-label classification task. Our binary classifier for the EB mode performs better than these ML methods with the area under precision-recall curve achieving 75%. The end preference of most TFs is consistent with low nucleosome occupancy around their binding site in GM12878 cells. The nucleosome occupancy data is used as an alternative dataset to confirm the superiority of our EB classifier., Conclusions: We develop the first ML-based approach for efficient and comprehensive analysis of nucleosome binding modes of TFs.

Background and Purposes: The pathogenic BRCA1/2 germline mutations contributed to Hereditary Breast and Ovarian Cancer (HBOC) susceptibility. The features of BRCA1/2 germline mutations in non-small cell lung cancer (NSCLC) have not been systematically studied. Here we performed the first study investigating the characteristics of pathogenic BRCA1/2 germline mutations in Chinese NSCLC patients and compared them with those from Chinese HBOC., Methods: Information on BRCA1/2 germline mutations from 9010 Chinese NSCLC patients were collected from available studies and analyzed, and compared with the BRCA1/2 germline mutations from Chinese HBOC BRCA1/2 database (LOVD database, 20,523 patients)., Results: 19 (20 carriers, 0.22 %) pathogenic BRCA1 and 60 (66 carriers, 0.73 %) pathogenic BRCA2 germline mutations from NSCLC were identified. The carrier frequency of BRCA1/2 in Chinese NSCLC patients (86/9010 = 0.95 %) was significantly lower than that in Chinese breast and ovary cancer patients (1481/20,523 = 7.2 %) (P < 0.001). We found that frameshift and nonsense mutations were the predominant types of BRCA1/2 mutation in NSCLC, with no obvious hot spot mutations. No significant difference in the ratio of frameshift and nonsense mutations was found between BRCA1 and BRCA2 in NSCLC. 5 out of 19 mutations in BRCA1 and 23 out of 60 mutations in BRCA2 were novel mutations found in NSCLC that have never been reported in Chinese HBOC. A trend of higher percentage of BRCA1 nonsense mutations in the carriers was revealed in NSCLC compared with HBOC, while no such difference was found in BRCA2 in all types of mutations., Conclusions: BRCA1/2 germline mutations from NSCLC exhibited distinct characteristics compared with those from HBOC in Chinese population, including lower carrier frequency than HBOC, higher ratio of nonsense mutations and carriers than HBOC, and novel BRCA1/2 germline mutations never found in HBOC.

Background: Obesity, a risk factor for many chronic diseases, is a potential independent risk factor for iron deficiency. Evidence has shown that chronic intermittent hypobaric hypoxia (CIHH) has protective or improved effects on cardiovascular, nervous, metabolic and immune systems. We hypothesized that CIHH may ameliorate the abnormal iron metabolism in obesity. This study was aimed to investigate the effect and the underlying mechanisms of CIHH on iron metabolism in high-fat-high-fructose-induced obese rats., Methods: Six to seven weeks old male Sprague-Dawley rats were fed with different diet for 16 weeks, and according to body weight divided into four groups: control (CON), CIHH (28-day, 6-h daily hypobaric hypoxia treatment simulating an altitude of 5000 m), dietary-induced obesity (DIO; induced by high fat diet and 10% fructose water feeding), and DIO + CIHH groups. The body weight, systolic arterial pressure (SAP), Lee index, fat coefficient, blood lipids, blood routine, iron metabolism parameters, interleukin6 (IL-6) and erythropoietin (Epo) were measured. The morphological changes of the liver, kidney and spleen were examined. Additionally, hepcidin mRNA expression in liver was analyzed., Results: The DIO rats displayed obesity, increased SAP, lipids metabolism disorders, damaged morphology of liver, kidney and spleen, disturbed iron metabolism, increased IL-6 level and hepcidin mRNA expression, and decreased Epo compared to CON rats. But all the aforementioned abnormalities in DIO rats were improved in DIO + CIHH rats., Conclusions: CIHH improves iron metabolism disorder in obese rats possibly through the down-regulation of hepcidin by decreasing IL-6 and increasing Epo.

Background: One of the most challenging tasks for bladder cancer diagnosis is to histologically differentiate two early stages, non-invasive Ta and superficially invasive T1, the latter of which is associated with a significantly higher risk of disease progression. Indeed, in a considerable number of cases, Ta and T1 tumors look very similar under microscope, making the distinction very difficult even for experienced pathologists. Thus, there is an urgent need for a favoring system based on machine learning (ML) to distinguish between the two stages of bladder cancer., Methods: A total of 1177 images of bladder tumor tissues stained by hematoxylin and eosin were collected by pathologists at University of Rochester Medical Center, which included 460 non-invasive (stage Ta) and 717 invasive (stage T1) tumors. Automatic pipelines were developed to extract features for three invasive patterns characteristic to the T1 stage bladder cancer (i.e., desmoplastic reaction, retraction artifact, and abundant pinker cytoplasm), using imaging processing software ImageJ and CellProfiler. Features extracted from the images were analyzed by a suite of machine learning approaches., Results: We extracted nearly 700 features from the Ta and T1 tumor images. Unsupervised clustering analysis failed to distinguish hematoxylin and eosin images of Ta vs. T1 tumors. With a reduced set of features, we successfully distinguished 1177 Ta or T1 images with an accuracy of 91-96% by six supervised learning methods. By contrast, convolutional neural network (CNN) models that automatically extract features from images produced an accuracy of 84%, indicating that feature extraction driven by domain knowledge outperforms CNN-based automatic feature extraction. Further analysis revealed that desmoplastic reaction was more important than the other two patterns, and the number and size of nuclei of tumor cells were the most predictive features., Conclusions: We provide a ML-empowered, feature-centered, and interpretable diagnostic system to facilitate the accurate staging of Ta and T1 diseases, which has a potential to apply to other types of cancer.

Background: A previous study by our team reported the prevalence of primary headache disorders and factors associated with headache among nurses in three hospitals in North China. The aim of this cross-sectional survey was to learn more about how medical nurses in South China were affected by headache. Additionally, we determined the prevalence of headache and measured the impact of headache among doctors in mainland China for the first time., Methods: Stratified random cluster sampling was used to select 280 physicians and 365 nurses from various departments in four hospitals in Sanya, which is one of southernmost cities in China. Information was collected on demographic data, occupational factors and headache characteristics by using a structured questionnaire., Results: Among 645 medical staff, 548 (85%) responded (doctors = 240, nurses = 308). Among the medical staff, the 1-year prevalence of primary headache disorders was 50%, with 25.9% experiencing migraine and 24.1% experiencing tension-type headache (TTH). The prevalence of migraine in female doctors was higher than that in female nurses, although this difference was not significant (32.4% vs. 29.8%, P = 0.628). Multivariate analysis showed that being female and working in other specialties (Emergency Department & Radiology Department) remained independent risk factors for migraine in doctors (OR 2.314 and 3.223). In nurses, being married was a risk factor for migraine (OR 3.728), and job titles remained an independent risk factor for migraine and TTH (OR 2.294 and 4.695). Working more than 6 night-shifts per month was associated with an increased prevalence of migraine and TTH in doctors; the same was true in nurses for migraine, but not for TTH., Conclusion: The prevalence of primary headache disorders in both nurses and doctors is higher than that in the general population in South China. Our study shows that occupation, geography and sex may play an important role. Further, female doctors are more susceptible than female nurses to migraine. The risk factors relevant to headache that were found in this study should provide an important reference for promoting occupational health in medical staff, especially female doctors in China.

Background: Posttranslational modification of proteins by small ubiquitin like modifier (SUMO) proteins play an important role during the developmental process and in response to abiotic stresses in plants. However, little is known about SUMOylation in peanut (Arachis hypogaea L.), one of the world's major food legume crops. In this study, we characterized the SUMOylation system from the diploid progenitor genomes of peanut, Arachis duranensis (AA) and Arachis ipaensis (BB)., Results: Genome-wide analysis revealed the presence of 40 SUMO system genes in A. duranensis and A. ipaensis. Our results showed that peanut also encodes a novel class II isotype of the SCE1, which was previously reported to be uniquely present in cereals. RNA-seq data showed that the core components of the SUMOylation cascade SUMO1/2 and SCE1 genes exhibited pod-specific expression patterns, implying coordinated regulation during pod development. Furthermore, both transcripts and conjugate profiles revealed that SUMOylation has significant roles during the pod development. Moreover, dynamic changes in the SUMO conjugates were observed in response to abiotic stresses., Conclusions: The identification and organization of peanut SUMO system revealed SUMOylation has important roles during stress defense and pod development. The present study will serve as a resource for providing new strategies to enhance agronomic yield and reveal the mechanism of peanut pod development.

Background: Clinical named entity recognition (CNER) is important for medical information mining and establishment of high-quality knowledge map. Due to the different text features from natural language and a large number of professional and uncommon clinical terms in Chinese electronic medical records (EMRs), there are still many difficulties in clinical named entity recognition of Chinese EMRs. It is of great importance to eliminate semantic interference and improve the ability of autonomous learning of internal features of the model under the small training corpus., Methods: From the perspective of deep learning, we integrated the attention mechanism into neural network, and proposed an improved clinical named entity recognition method for Chinese electronic medical records called BiLSTM-Att-CRF, which could capture more useful information of the context and avoid the problem of missing information caused by long-distance factors. In addition, medical dictionaries and part-of-speech (POS) features were also introduced to improve the performance of the model., Results: Based on China Conference on Knowledge Graph and Semantic Computing (CCKS) 2017 and 2018 Chinese EMRs corpus, our BiLSTM-Att-CRF model finally achieved better performance than other widely-used models without additional features(F1-measure of 85.4% in CCKS 2018, F1-measure of 90.29% in CCKS 2017), and achieved the best performance with POS and dictionary features (F1-measure of 86.11% in CCKS 2018, F1-measure of 90.48% in CCKS 2017). In particular, the BiLSTM-Att-CRF model had significant effect on the improvement of Recall., Conclusions: Our work preliminarily confirmed the validity of attention mechanism in discovering key information and mining text features, which might provide useful ideas for future research in clinical named entity recognition of Chinese electronic medical records. In the future, we will explore the deeper application of attention mechanism in neural network.

Background: The cultivated peanut is an important oil and cash crop grown worldwide. To meet the growing demand for peanut production each year, genetic studies and enhanced selection efficiency are essential, including linkage mapping, genome-wide association study, bulked-segregant analysis and marker-assisted selection. Specific locus amplified fragment sequencing (SLAF-seq) is a powerful tool for high density genetic map (HDGM) construction and quantitative trait loci (QTLs) mapping. In this study, a HDGM was constructed using SLAF-seq leading to identification of QTL for seed weight and size in peanut., Results: A recombinant inbred line (RIL) population was advanced from a cross between a cultivar 'Huayu36' and a germplasm line '6-13' with contrasting seed weight, size and shape. Based on the cultivated peanut genome, a HDGM was constructed with 3866 loci consisting of SLAF-seq and simple sequence repeat (SSR) markers distributed on 20 linkage groups (LGs) covering a total map distance of 1266.87 cM. Phenotypic data of four seed related traits were obtained in four environments, which mostly displayed normal distribution with varied levels of correlation. A total of 27 QTLs for 100 seed weight (100SW), seed length (SL), seed width (SW) and length to width ratio (L/W) were identified on 8 chromosomes, with LOD values of 3.16-31.55 and explaining phenotypic variance (PVE) from 0.74 to 83.23%. Two stable QTL regions were identified on chromosomes 2 and 16, and gene content within these regions provided valuable information for further functional analysis of yield component traits., Conclusions: This study represents a new HDGM based on the cultivated peanut genome using SLAF-seq and SSRs. QTL mapping of four seed related traits revealed two stable QTL regions on chromosomes 2 and 16, which not only facilitate fine mapping and cloning these genes, but also provide opportunity for molecular breeding of new peanut cultivars with improved seed weight and size.

Background: Puccinellia tenuiflora is the most saline-alkali tolerant plant in the Songnen Plain, one of the three largest soda saline-alkali lands worldwide. Here, we investigated the physicochemical properties of saline-alkali soils from the Songnen Plain and sequenced the transcriptomes of germinated P. tenuiflora seedlings under long-term treatment (from seed soaking) with saline-alkali soil extracts., Results: We found that the soils from Songnen Plain were reasonably rich in salts and alkali; moreover, the soils were severely deficient in nitrogen [N], phosphorus [P], potassium [K] and several other mineral elements. This finding demonstrated that P. tenuiflora can survive from not only high saline-alkali stress but also a lack of essential mineral elements. To explore the saline-alkali tolerance mechanism, transcriptional analyses of P. tenuiflora plants treated with water extracts from the saline-alkali soils was performed. Interestingly, unigenes involved in the uptake of N, P, K and the micronutrients were found to be significantly upregulated, which indicated the existence of an efficient nutrition-uptake system in P. tenuiflora. Compared with P. tenuiflora, the rice Oryza sativa was hypersensitive to saline-alkali stress. The results obtained using a noninvasive microtest techniques confirmed that the uptake of NO 3 - and NH 4 + and the regulatory flux of Na + and H + were significantly higher in the roots of P. tenuiflora than in those of O. sativa. In the corresponding physiological experiments, the application of additional nutrition elements significantly eliminated the sensitive symptoms of rice to saline-alkali soil extracts., Conclusions: Our results imply that the survival of P. tenuiflora in saline-alkali soils is due to a combination of at least two regulatory mechanisms and the high nutrient uptake capacity of P. tenuiflora plays a pivotal role in its adaptation to those stress. Taken together, our results highlight the role of nutrition uptake in saline-alkali stress tolerance in plants.

Background: To determine the treatment behaviors among a community-based cohort of chronic hepatitis B virus (HBV)-infected persons and to examine the disease progression among non-antiviral-treated HBV-infected cases after 5 years of follow-up., Methods: We conducted a community-based prospective study on people with chronic HBV infection in mainland China from 2009 to 2014. In 2009, we recruited participants who were identified as HBV infected in 2006 in a national sero-survey. A face-to-face follow-up investigation was completed in 2014, and the personal information, the clinical diagnosis provided at the last hospital visit, the HBV antiviral treatment history, and the insurance type was collected for each patient for analysis. Multivariable logistic regression was used to identify factors that are associated with active medical care- seeking and antiviral treatments., Results: Among the 2422 chronic HBV-infected patients recruited in 2009, 1784 (73.7%) were followed-up to 2014, and 638 (35.8%) had sought medical care in hospitals; among them, 140 (21.9%) received antiviral treatments. The lowest medical care-seeking rate (26%) was in participants over 50-year old. We determined that the frequency of medical care-seeking was higher among those participants living in urban areas (aRR = 1.3, 95% CI:1.0-1.6), those in 0-19-year old (aRR = 1.5, 95% CI:1.1-2.1), 20-39-year old (aRR = 2.2, 95% CI:1.7-3.0) and 40-49-year old (aRR = 1.5, 95% CI:1.1-2.0), and persons with insurance of the type Urban residents' basic medical insurance (URBMI) or Commercial health insurance (CHI) (aRR = 2.5, 95% CI:1.7-3.6) and New Rural Cooperative Medical System (NRCMS) (aRR = 1.9, 95% CI:1.4-2.6). Patients were more likely to receive antiviral treatment if they were 20-39-year old (aRR = 0.4, 95% CI:0.3-0.7), had insurance of the type URBMI or CHI (aRR = 2.6, 95% CI:1.1-6.3) or NRCMS (aRR = 3.0, 95% CI:1.3-6.9) and were treated at prefecture and above-level hospitals (aRR = 2.0, 95% CI:1.4-3.0). Among non-antiviral-treated HBV-infected cases, we found the annual rates for HBsAg sero-clearance, progress to cirrhosis and HCC were 1.0, 0.6 and 0.2%, respectively., Conclusion: The rates of medical care-seeking and antiviral treatment were low among community-based chronic HBV-infected persons, thus we recommend improving the insurance policies for HBV-infected persons to increase the antiviral treatment rate, and conducting extensive education to promote HBV-infected patients actively seeking medical care from hospitals.

Purpose: We propose a collaborative and secure transmission scheme in order to safely and efficiently transmit medical data and provide telemedicine services, lighten the load on wireless access networks, and improve the quality of medical treatment such as surgery., Methods: First, the transmission technology based on opportunistic networks is used to upload patient physiological data and share medical information. Second, we propose a trusted transfer scheme based on the circle of friends, which is constructed with historical encounters and social features of nodes. This scheme takes the forwarding policy of each packet by close friends to effectively prevent the participation of strangers, and avoid privacy issues and deal with selfish behaviors. At the same time, the structure of friend circle is beneficial to the improvement of medical data transmission. Third, we present a lossless compression scheme with less computation and higher compression ratio to reduce the amount of medical data and improve the performance of the transmission., Results: The experimental results show that the proposed scheme is effective and has good transmission performance while ensuring the safety and reliability of media data., Conclusion: The mobile healthcare faces some challenges such as the vastness of medical data and sensitivity of patient information. Using opportunistic networks to transmit medical data in mobile healthcare is a good solution, which can effectively divert and offload the data traffic of mobile Internet. The structure of friend circles and the technology of data compression are beneficial to safely and efficiently transmit the patient's physiological parameters and medical health information.

Background: The topological landscape of gene interaction networks provides a rich source of information for inferring functional patterns of genes or proteins. However, it is still a challenging task to aggregate heterogeneous biological information such as gene expression and gene interactions to achieve more accurate inference for prediction and discovery of new gene interactions. In particular, how to generate a unified vector representation to integrate diverse input data is a key challenge addressed here., Results: We propose a scalable and robust deep learning framework to learn embedded representations to unify known gene interactions and gene expression for gene interaction predictions. These low- dimensional embeddings derive deeper insights into the structure of rapidly accumulating and diverse gene interaction networks and greatly simplify downstream modeling. We compare the predictive power of our deep embeddings to the strong baselines. The results suggest that our deep embeddings achieve significantly more accurate predictions. Moreover, a set of novel gene interaction predictions are validated by up-to-date literature-based database entries., Conclusion: The proposed model demonstrates the importance of integrating heterogeneous information about genes for gene network inference. GNE is freely available under the GNU General Public License and can be downloaded from GitHub ( https://github.com/kckishan/GNE ).

Background: Common wheat (Triticum aestivum L.) is one of the most important food crops worldwide. Wheat spike-layer uniformity related traits (SLURTs) were complex traits that directly affect yield potential and appearance. In this study, quantitative trait locus (QTL) for five SLURTs among inter-tillers were first documented using a recombinant inbred line (RIL) mapping population derived from a cross between Kenong9204 and Jing411 (represented by KJ-RILs). Genetic relationships between SLURTs and yield were characterized in detail., Results: The trait phenotypic performances for the 188 KJ-RILs and their parents were evaluated in eight different environments. The genetic data included in a high-density genetic map derived from the Affymetrix 660 K SNP Array and the corresponding genotypes in each lines. Of 99 putative additive QTL 11 were stable across environments and 57 showed significant additive-by-environment interaction effects. These QTL individually explained 1.05-39.62% of the phenotypic variance, with log of odds (LOD) values ranging from 2.00 to 34.01. Genetic relationships between SLURTs and yield indicated that plants with slight uneven spike spatial distribution should be an ideotype for super high-yield in wheat., Conclusions: The present study will provide assistance in understanding the genetic relationships between SLURTs and yield potential. The 11 stable QTL for SLURTs identified herein may facilitate breeding new wheat varieties with scientifically reasonable spike-layer distribution by marker assisted selection.

Background: Functional characterization of single nucleotide variants (SNVs) involves two steps, the first step is to convert DNA to protein and the second step is to visualize protein sequences with their structures. As massively parallel sequencing has emerged as a leading technology in genomics, resulting in a significant increase in data volume, direct visualization of SNVs together with associated protein sequences/structures in a new user interface (UI) would be a more effective way to assess their potential effects on protein function., Results: We have developed BioVR, an easy-to-use interactive, virtual reality (VR)-assisted platform for integrated visual analysis of DNA/RNA/protein sequences and protein structures using Unity3D and the C# programming language. It utilizes the cutting-edge Oculus Rift, and Leap Motion hand detection, resulting in intuitive navigation and exploration of various types of biological data. Using Gria2 and its associated gene product as an example, we present this proof-of-concept software to integrate protein and nucleic acid data. For any amino acid or nucleotide of interest in the Gria2 sequence, it can be quickly linked to its corresponding location on Gria2 protein structure and visualized within VR., Conclusions: Using innovative 3D techniques, we provide a VR-based platform for visualization of DNA/RNA sequences and protein structures in aggregate, which can be extended to view omics data.

Background: Most plant viruses depend on vector insects for transmission. Upon viral infection, virus-derived small interfering RNAs (vsiRNAs) can target both viral and host transcripts. Rice stripe virus (RSV) is a persistent-propagative virus transmitted by the small brown planthopper (Laodelphax striatellus, Fallen) and can cause a severe disease on rice., Results: To investigate how vsiRNAs regulate gene expressions in the host plant and the insect vector, we analyzed the expression profiles of small RNAs (sRNAs) and mRNAs in RSV-infected rice and RSV-infected planthopper. We obtained 88,247 vsiRNAs in rice that were predominantly derived from the terminal regions of the RSV RNA segments, and 351,655 vsiRNAs in planthopper that displayed relatively even distributions on RSV RNA segments. 38,112 and 80,698 unique vsiRNAs were found only in rice and planthopper, respectively, while 14,006 unique vsiRNAs were found in both of them. Compared to mock-inoculated rice, 273 genes were significantly down-regulated genes (DRGs) in RSV-infected rice, among which 192 (70.3%) were potential targets of vsiRNAs based on sequence complementarity. Gene ontology (GO) analysis revealed that these 192 DRGs were enriched in genes involved in kinase activity, carbohydrate binding and protein binding. Similarly, 265 DRGs were identified in RSV-infected planthoppers, among which 126 (47.5%) were potential targets of vsiRNAs. These planthopper target genes were enriched in genes that are involved in structural constituent of cuticle, serine-type endopeptidase activity, and oxidoreductase activity., Conclusions: Taken together, our results reveal that infection by the same virus can generate distinct vsiRNAs in different hosts to potentially regulate different biological processes, thus reflecting distinct virus-host interactions.

Background: The World Health Organization recommends all men who have sex with men (MSM) receive Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) testing. MSM in China are a high-risk group for HBV and HCV infection, but test uptake is low. Crowdsourcing invites a large group to solve a problem and then shares the solution with the public. This nationwide online randomized controlled trial will evaluate the effectiveness of a crowdsourced intervention to increase HBV and HCV testing among MSM in China., Methods: Seven hundred MSM will be recruited through social media operated by MSM organizations in China. Eligible participants will be born biologically male, age 16 years or older, report previous anal sex with another man, and reside in China. After completing a baseline online survey, participants will be randomly assigned to intervention or control arms with a 1:1 allocation ratio. The intervention will include two components: (1) a multimedia component will deliver two videos and two images promoting HBV and HCV testing developed through a crowdsourcing contest in China; (2) a participatory component will invite men to submit suggestions for how to improve crowdsourced videos and images. The control arm will not view any images or videos and will not be invited to submit suggestions. All participants will be offered reimbursement for HBV and HCV testing costs. The primary outcome is HBV and HCV test uptake confirmed through electronic submission of test report photos within four weeks of enrolment. Secondary outcomes include self-reported HBV and HCV test uptake, HBV vaccination uptake, and change in stigma toward people living with HBV after four weeks. Primary and secondary outcomes will be calculated using intention to treat and as-exposed analyses and compared using two-sided 95% confidence intervals., Discussion: Few previous studies have evaluated interventions to increase HBV and HCV testing in middle-income countries with a high burden of hepatitis. Delivering a crowdsourced intervention using social media is a novel approach to increasing hepatitis testing rates. HBV and HCV test uptake will be confirmed through test report photos, avoiding the limitations of self-reported testing outcomes., Trial Registration: NCT03482388 (29 March 2018).

This article [1] is retracted at request of the Editor. After publication of this article [1] concerns were raised regarding aspects of the methodology, including the choice of stains being inappropriate or inadequate to answer the research question. A discrepancy was also noted between the number of groups described in the methods and the number of groups presented in some of the figures. Furthermore the western blot images did not entirely correspond with the information reported in the results. For these reasons the conclusions of the study cannot be considered to be supported by the data. All authors agree to this retraction.

Background: One central building block of population genetics is the fixation probability. It is a probabilistic understanding of the eventual fate of new mutations. Moreover, the fixation probability of new beneficial mutations plays an important effect on the adaptation of populations to environmental challenges. Great progress has been made in the study of the beneficial mutations that increases offspring number. However, the fixation probability of beneficial mutations with a shorter generation time under various genetic and ecological conditions has not been explored., Results: Here we extend the classical result of the fixation probability of beneficial mutations obtained by Haldane, and estimate the fixation probability of a beneficial mutation with a reduced generation time in a changing environment. Assuming that the selective advantage is very small, we concentrate all the changing factors of environment on a single quantity: effective selective advantage. Using a time-dependent branching process, we get the analytic approximation for the fixation probability of beneficial mutations that decrease the generation time. Then, we apply this approximation to four interesting biological cases., Conclusions: In these instances, we show the comparison of the approximation with the accurate values. We find that they are consistent, demonstrating the effectiveness of our result for the fixation probability of beneficial mutations conferring a reduced replication time.

Background: S100A9 protein, which is recently classified as a novel damage associated molecular pattern, is released from stressed cells undergoing necrosis or secreted by living cells undergoing a stress that act as endogenous danger signal associated with infection, tissue damage and cancer. Here, we evaluated the relationship of serum S100A9 with viral replication and liver necroinflammation in patients with chronic hepatitis B (CHB) infection., Methods: A total of one hundred and eighty-three recruited patients with CHB infection underwent liver biopsy for grading of necroinflammation (G) and staging of fibrosis (S). Forty-nine healthy individuals were included as healthy controls (HCs). Serum S100A9 levels were determined by enzyme-linked immunosorbent assay. Correlations of serum S100A9 with viral replication and liver necroinflammation were analyzed. The receiver operating characteristic curve was used to assess the discriminating power of serum S100A9 to grade liver necroinflammation (G). Liver normal L02 cells were transfected with a HBV plasmid, and S100A9 levels were determined., Results: Serum S100A9 levels were increased in CHB patients compared to HCs. Intrahepatic immunoreactivity for S100A9 was enhanced in liver sample from CHB patients. Infection of HBV also resulted in an elevated S100A9 expression in L02 cells. Serum S100A9 was correlated with the serum HBV DNA levels. CHB patients with moderate-to-severe liver necroinflammation (G ≥ 2) showed significantly higher serum S100A9 levels than those without or with mild necroinflammation (G < 2). In patients with normal ALT levels, the area under the curve (AUC) of S100A9 for discriminating patients with moderate-to-severe necroinflammation (G ≥ 2) was 0.791 [95% confidence interval (CI), 0.670-0.913] with 91.7% sensitivity, 65.0% specificity and 78.3% accuracy. In patients with an alanine aminotransferase (ALT) < 2 upper limit of normal, the AUC of S100A9 for discriminating patients with moderate-to-severe necroinflammation (G ≥ 2) was 0.826 (95% CI, 0.729-0.923) with 87.9% sensitivity, 72.5% specificity and 80.2% accuracy., Conclusions: HBV infection may enhance S100A9 expression. Serum S100A9 levels are correlated with viral load. Serum S100A9 has potential to discriminate the grades of liver necroinflammation, particularly in CHB patients with normal or mildly increased ALT levels.

Background: Saline fluid nebulization is highly recommend to combat the complications following tracheostomy, yet the understandings on the role of osmolality in saline solution for nebulization remain unclear., Objectives: To investigate the biological changes in the early stage after tracheostomy, to verify the efficacy of saline fluid nebulization and explore the potential role of osmolality of saline nebulization after tracheostomy., Methods: Sprague-Dawley rats undergone tracheostomy were taken for study model, the sputum viscosity was detected by rotational viscometer, the expressions of TNF-α, AQP4 in bronchoalveolar lavage fluid were assessed by western blot analysis, and the histological changes in endothelium were evaluated by HE staining and scanning electron microscopy (SEM)., Results: Study results revealed that tracheostomy gave rise to the increase of sputum viscosity, TNF-α and AQP4 expression, mucosa and cilia damage, yet the saline fluid nebulization could significantly decrease the changes of those indicators, besides, the hypertonic, isotonic and hypertonic saline nebulization produced different efficacy., Conclusions: Osmolality plays an important role in the saline fluid nebulization after tracheostomy, and 3% saline fluid nebulization seems to be more beneficial, further studies on the role of osmolality in saline fluid nebulization are warranted.