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This study aimed to investigate the probable existence of a causal relationship between sleep phenotypes and proliferative diabetic retinopathy (PDR). Single nucleotide polymorphisms associated with sleep phenotypes were selected as instrumental variables at the genome-wide significance threshold (P < 5 × 10−8). Inverse‐variance weighted was applied as the primary Mendelian randomization (MR) analysis method, and MR Egger regression, weighted median, simple mode, and weighted mode methods were used as complementary analysis methods to estimate the causal association between sleep phenotypes and PDR. Results indicated that genetically predicted sleep phenotypes had no causal effects on PDR risk after Bonferroni correction (P = 0.05/10) [Chronotype: P = 0.143; Daytime napping: P = 0.691; Daytime sleepiness: P = 0.473; Insomnia: P = 0.181; Long sleep duration: P = 0.671; Morning person:P = 0.113; Short sleep duration: P = 0.517; Obstructive sleep apnea: P = 0.091; Sleep duration: P = 0.216; and snoring: P = 0.014]. Meanwhile, there are no reverse causality for genetically predicted PDR on sleep phenotypes [Chronotype: P = 0.100; Daytime napping: P = 0.146; Daytime sleepiness: P = 0.469; Insomnia: P = 0.571; Long sleep duration: P = 0.779; Morning person: P = 0.040; Short sleep duration: P = 0.875; Obstructive sleep apnea: P = 0.628; Sleep duration: P = 0.896; and snoring: P = 0.047]. This study's findings did not support the causal effect of between sleep phenotypes and PDR. Whereas, longitudinal studies can further verify results validation. [ABSTRACT FROM AUTHOR]

Enhancing carbon productivity (CP) is key to achieving carbon reduction goals while maintaining economic growth. Digital technology plays a significant role in improving CP. Based on panel data from 136 countries worldwide from 2000 to 2020, this study empirically examines the impact of digitalization on CP and its mechanisms using fixed-effects and mediation models. The conclusions are as follows: (1) Overall, digitalization significantly enhances CP. (2) In terms of the mechanism, digitalization primarily improves CP through technological innovation and mitigating income inequality. (3) In terms of the quantile regression results, as the quantile level of CP increases, the promoting effect of digitalization on CP gradually strengthens. (4) From the perspective of heterogeneity among regions, income levels and human capital levels, digitalization has the greatest promotion effect on carbon productivity in European countries, high-income countries and high human capital countries. This study provides a reference for policymakers worldwide to use digital technology in achieving carbon emission reduction targets. [ABSTRACT FROM AUTHOR]

The authentic SARS-CoV-2 requires to be handled in Biosafety Level 3 laboratories, which restrains investigation by the broader scientific community. Here, we report the development of a novel SARS-CoV-2 viral vector composed of all 4 SARS-CoV-2 structural proteins, the packaging signal sequence of SARS-CoV-2, a reporter gene, and an RNA amplification component of Venezuelan equine encephalitis virus (VEEV). This VEE-SARS-CoV-2 viral vector transduces target cells in an ACE2-dependent manner, and all 4 structural proteins of SARS-CoV-2 are indispensable for its transduction activity. Comparative studies show that the incorporation of the VEEV self-amplification mechanism increases the gene expression level by ~ 65-fold and extends the transgene expression up to 11 days in transduced cells. Additionally, we demonstrated the significant applications of this new VEE-SARS-CoV-2 vector for neutralizing antibody quantification and antiviral drug testing. The VEE-SARS-CoV-2 vectors developed will be an important and versatile tool for investigating SARS-CoV-2 molecular virology, developing antiviral agents targeting receptor binding, and studying RNA genome packaging and function of the essential but not well studied structural proteins of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The authentic SARS-CoV-2 requires to be handled in Biosafety Level 3 laboratories, which restrains investigation by the broader scientific community. Here, we report the development of a novel SARS-CoV-2 viral vector composed of all 4 SARS-CoV-2 structural proteins, the packaging signal sequence of SARS-CoV-2, a reporter gene, and an RNA amplification component of Venezuelan equine encephalitis virus (VEEV). This VEE-SARS-CoV-2 viral vector transduces target cells in an ACE2-dependent manner, and all 4 structural proteins of SARS-CoV-2 are indispensable for its transduction activity. Comparative studies show that the incorporation of the VEEV self-amplification mechanism increases the gene expression level by ~ 65-fold and extends the transgene expression up to 11 days in transduced cells. Additionally, we demonstrated the significant applications of this new VEE-SARS-CoV-2 vector for neutralizing antibody quantification and antiviral drug testing. The VEE-SARS-CoV-2 vectors developed will be an important and versatile tool for investigating SARS-CoV-2 molecular virology, developing antiviral agents targeting receptor binding, and studying RNA genome packaging and function of the essential but not well studied structural proteins of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The binary blend materials containing the modified recycled rubber powder with maleic a hydride modified polypropylene thermoplastic elastomer were prepared by dynamic vulcanization and blended with a variety of additives such as activated agent, accelerator, solubilizer, and the crosslinking agent. The thermal properties and mechanical properties including tensile strengths and impact strengths of pristine rubber, polypropylene and their corresponding binary blends were investigated. Besides, the effects of the amount of rubber powder, polypropylene, crosslinking agent, accelerator, activator, and solvent were studied and the microstructures of the pristine rubber, pristine polypropylene, and their corresponding binary blends were observed by scanning electron microscopy. It was found that the compatibilizer could effectively disperse the size of 120 mesh of recycled rubber powder into the polypropylene in the same manner and the homogeneous tear section of the rubber/polypropylene thermoplastic elastomer was obtained. The results on the effects of additives on mechanical and morphological properties of recycled rubber/polypropylene binary blends guide the rational design of novel polymeric composites from recycled polymeric materials. [ABSTRACT FROM AUTHOR]

The bacterial phoD gene encoding alkaline phosphatase (ALP) plays an important role in the release of soluble reactive phosphorus (SRP) from organic phosphorus in ecosystems. However, phoD gene diversity and abundance in ecosystems is poorly understood. In the present study, we sampled the surface sediments and the overlying water of Sancha Lake at 9 different sampling sites, a typical eutrophic sub-deep freshwater lake in China, in April 15 (spring) and November 3 (autumn), 2017. High-throughput sequencing and qPCR were performed to analyze the diversity and abundance of the bacterial phoD gene in the sediments. We further discussed the relationships between the diversity and abundance of the phoD gene and environmental factors and ALP activity. A total of 881,717 valid sequences were obtained from 18 samples and were classified into 41 genera, 31 families, 23 orders, 12 classes, and 9 phyla and grouped into 477 OTUs. The dominant phyla were Proteobacteria and Actinobacteria. The phylogenetic tree based on the sequences of the phoD gene was plotted and composed of three branches. The genetic sequences were aligned predominantly with genera Pseudomonas, Streptomyces, Cupriavidus, and Paludisphaer. The phoD-harboring bacterial community structure showed a significant difference in spring and autumn, but no apparent spatial heterogeneity. The phoD gene abundances at different sampling points were significantly higher in autumn than in spring. In autumn and spring, the phoD gene abundance was significantly higher in the tail of lake and where cage culture used to be intensive. pH value, dissolved oxygen (DO), total organic carbon (TOC), ALP, and phosphorus were important environmental factors affecting the diversity of the phoD gene and the phoD-harboring bacterial community structure. Changes in phoD-harboring bacterial community structure, phoD gene abundance, and ALP activity were negatively correlated with SRP in overlying water. Our study indicated phoD-harboring bacteria in the sediments of Sancha Lake with the characteristics of high diversity and significant spatial and temporal heterogeneity in abundance and community structure, which played a important role in the release of SRP. [ABSTRACT FROM AUTHOR]

Angiogenesis is a physiological process for the formation of new blood vessels from the pre-existing vessels and it has a vital role in the survival and growth of neoplasms. During tumor angiogenesis, the activation of the gene transcriptions in vascular endothelial cells (ECs) plays an essential role in the promotion of EC proliferation, migration, and vascular network development. However, the molecular mechanisms underlying transcriptional regulation of EC and tumor angiogenesis remains to be fully elucidated. Here we report that the transcription factor Yin Yang 1 (YY1) in ECs is critically involved in tumor angiogenesis. First, we utilized a tamoxifen-inducible EC-specific YY1 deficient mouse model and showed that YY1 deletion in ECs inhibited the tumor growth and tumor angiogenesis. Using the in vivo matrigel plug assay, we then found that EC-specific YY1 ablation inhibited growth factor-induced angiogenesis. Furthermore, vascular endothelial growth factor (VEGF)-induced EC migration was diminished in YY1-depleted human umbilical vein endothelial cells (HUVECs). Finally, a rescue experiment revealed that YY1-regulated BMP6 expression in ECs was involved in EC migration. Collectively, our results demonstrate that endothelial YY1 has a crucial role in tumor angiogenesis and suggest that targeting endothelial YY1 could be a potential therapeutic strategy for cancer treatment. [ABSTRACT FROM AUTHOR]

The growth of winter wheat consumes a substantial amounts of water, and precipitation in most years cannot meet the water demand for the normal growth of winter wheat. The unsuitable irrigation strategies waste a large number of water resource, and the low water use efficiency has become the main factor limiting wheat yields. This research explored the effects of different cultivation managements on water consumption characteristics, water utilization efficiency, and grain yields of winter wheat. A field experiment, in which 4 cultivation managements including traditional cultivation management (T1), optimized cultivation management compared with T1 (T2), super high-yield cultivation management (T3) and optimized cultivation management compared with T3 (T4), was conducted during 2008–2010 to measure the above parameters. The results showed that different cultivation managements had significant effects on the total water consumption amounts and water source compositions. Total water consumption amounts in T1 and T3 managements were significantly higher than that in T2 and T4 managements, possibly from irrigation water. T2 and T4 managements remarkably increased the uptake and utilization of soil storage water and precipitation amounts. T3 and T1 managements increased and decreased water consumption in upper (0–40 cm) and lower (60–100 cm) soil layers, respectively, while effectively increased the consumption of storage water in middle and lower soil layers (60–100 cm) and yield water use efficiency (WUEY), precipitation water use efficiency (WUEP), soil water use efficiency (WUES), irrigation water use efficiency (WUEI), and irrigation efficiency (IE) in T4 and T2 managements were higher than those in T3 and T1, respectively. Total water consumption amounts markedly raised in T1 and T3 managements, whereas their soil storage water amounts utilization declined. T2 and T4 managements reduced irrigation water amounts and optimized the water and fertilizer supplies, resulting in significant increase in WUES and WUEI. Collectively, our results suggest that synergetic improving the water uptake and utilization of irrigation water and soil storage water can be the primary means to increase the grain yields and WUE. [ABSTRACT FROM AUTHOR]

This study aimed to analyze peripheral blood lymphocyte subsets in lupus nephritis (LN) patients and use machine learning (ML) methods to establish an effective algorithm for predicting co-infection in LN. This study included 111 non-infected LN patients, 72 infected LN patients, and 206 healthy controls (HCs). Patient information, infection characteristics, medication, and laboratory indexes were recorded. Eight ML methods were compared to establish a model through a training group and verify the results in a test group. We trained the ML models, including Logistic Regression, Decision Tree, K-Nearest Neighbors, Support Vector Machine, Multi-Layer Perceptron, Random Forest, Ada boost, Extreme Gradient Boosting (XGB), and further evaluated potential predictors of infection. Infected LN patients had significantly decreased levels of T, B, helper T, suppressor T, and natural killer cells compared to non-infected LN patients and HCs. The number of regulatory T cells (Tregs) in LN patients was significantly lower than in HCs, with infected patients having the lowest Tregs count. Among the ML algorithms, XGB demonstrated the highest accuracy and precision for predicting LN infections. The innate and adaptive immune systems are disrupted in LN patients, and monitoring lymphocyte subsets can help prevent and treat infections. The XGB algorithm was recommended for predicting co-infection in LN. [ABSTRACT FROM AUTHOR]

As a typical sub-deep reservoir in the upper reaches of the Yangtze River in the southwest region, Zhangjiayan Reservoir is also an important source of drinking water. Exploring the role of microorganisms in the material cycle of water bodies is of great significance for preventing the exacerbation of eutrophication in the reservoir. In this study, water samples from the overlying water of five points in the reservoir were collected four times in spring (April), summer (July), autumn (November), and winter (January) of 2022–2023 using a gas-tight water sampler. Physicochemical factors were measured, and the microbial community structure was analyzed by high-throughput MiSeq sequencing of the V3–V4 hypervariable region of 16S rRNA gene in order to explore the relationship between physicochemical factors and microbial community structure and the dominant microbial populations that affect eutrophication of the reservoir. The following results were obtained through analysis. Among the 20 overlying water samples from Zhangjiayan Reservoir, a total of 66 phyla, 202 classes, 499 orders, 835 families, 1716 genera, and 27,904 ASVs of the bacterial domain were detected. The phyla Proteobacteria and Actinobacteria were dominant in the microbial community of the overlying water in Zhangjiayan Reservoir. At the genus level, hgcI_clade and Actinobacteria had the highest abundance and was the dominant population. The microbial community in the water of Zhangjiayan Reservoir has a high level of diversity. The diversity index ranked by numerical order was winter > autumn > summer > spring. Significant differences were found in the composition and structure of the microbial community between the spring/summer and autumn/winter seasons (p < 0.05). Total phosphorus, dissolved total phosphorus, soluble reactive phosphorus, and dissolved oxygen have a significant impact on the composition and structure of the microbial community (p < 0.01). The bacterial community in the overlying water of Zhangjiayan Reservoir showed a mainly positive correlation. Sphingomonas, Brevundimonas, and Blastomonas were the central populations of the bacterial community in the overlying water of Zhangjiayan Reservoir. This study indicates that environmental factors, such as phosphorus and other nutrients, have a significant impact on the formation of the microbial community structure in different seasons. Sphingomonas, Brevundimonas, and Blastomonas are key populations that may have a significant impact on eutrophication in Zhangjiayan Reservoir. [ABSTRACT FROM AUTHOR]

Tunable terahertz (THz) functional devices have exhibited superior performances due to the use of active materials, such as liquid crystals, graphene, and semiconductors. However, the tunable range of constitutive parameters of materials is still limited, which leads to the low modulation depth of THz devices. Here, we demonstrate a broadband tunable THz absorber based on hybrid vanadium dioxide (VO2) metamaterials. Unlike other phase change materials, VO2 exhibits an insulator-to-metal transition characteristic and the conductivity can be increased by 4–5 orders of magnitude under external stimulus including electric fields, optical, and thermal pumps. Based on the unique transition character of VO2, the maximum tunable range of the proposed absorber can be realized from 5% to 100% by an external thermal excitation. Meanwhile, an absorption greater than 80% in a continuous range with a bandwidth about 2.0 THz can be obtained when VO2 is in its metal phase at high temperature. Furthermore, the absorber is insensitive to the incident angle up to 50° and such a broadband THz absorber can be used in applications including imaging, modulating, cloaking, and so on. [ABSTRACT FROM AUTHOR]

Development of hydrogen as clean and efficient energy carrier for future is imperative. Water electrolysis, is considered as one of the most promising ways to realize large-scaled hydrogen production. However, a big obstacle of it is to reduce the electric energy consumption for water oxidation in the anode. Engineering of hierarchical architectures on the electrocatalysts could provide abundant active sites and thus boost the sluggish reaction kinetics of water oxidation. Herein, a sequential synthesis method is developed for in-situ growth of ultrathin Co9S8 nanosheets vertically aligned on N and S co-doped reduced graphene oxide (Co9S8/N,S-rGO) as novel and efficient electrocatalysts for water splitting. This architecture with vertically aligned ultrathin Co9S8 nanosheets on N,S/rGO is adopted to facilitate the electron transport and exposure of active sites. Benefiting from the synergetic catalysis between Co9S8 nanosheets and N,S/rGO, Co9S8/N,S-rGO presents remarkable electrocatalytic activity towards oxygen evolution with a low overpotential (266 mV to achieve current density of 10 mA cm−2), small Tafel slope of 75.5 mV dec−1, and good durability in alkaline medium. This remarkable OER electrocatalytic activity is outperforms most of the known noble-metal-free electrocatalysts. [ABSTRACT FROM AUTHOR]

Mandrill (Mandrillus sphinx) is a primate species, which belongs to the Old World monkey (Cercopithecidae) family. It is closely related to human, serving as a model for human health related research. However, the genetic studies on and genomic resources of mandrill are limited, especially in comparison to other primate species. Here we produced 284 Gb data, providing 96-fold coverage (considering the estimated genome size of 2.9 Gb), to construct a reference genome for the mandrill. The assembled draft genome was 2.79 Gb with contig N50 of 20.48 Kb and scaffold N50 of 3.56 Mb. We annotated the mandrill genome to find 43.83% repeat elements, as well as 21,906 protein-coding genes. The draft genome was of good quality with 98% gene annotation coverage by Benchmarking Universal Single-Copy Orthologs (BUSCO). Based on comparative genomic analyses of the Major Histocompatibility Complex (MHC) of the immune system in mandrill and human, we found that 17 genes in the mandrill that have been associated with disease phenotypes in human such as Lung cancer, cranial volume and asthma, barbored amino acids changing mutations. Gene family analyses revealed expansion of several genes, and several genes associated with stress environmental adaptation and innate immunity responses exhibited signatures of positive selection. In summary, we established the first draft genome of the mandrill of value for studies on evolution and human health. [ABSTRACT FROM AUTHOR]

Deep vein thrombosis (DVT) is common seen in patients undergoing spine surgery. However, its prevalence and associated risk factors have not been well understood yet. This retrospective case-cohort study was designed to investigate risk factors for postoperative DVT using retrospectively collected data from department of spine surgery between 07/2013 and 07/2014. Univariate analysis and binary logistic regression analysis were used to determine risk factors for DVT. A total of 861 patients were admitted into DVT-associated analyses, including 410 males and 451 females, aged from 15 to 87 years old (median 54, IQR 18). Of them, 147 cases (17%) sustained postoperative DVT. DVT incidence was 15.9% in patients undergoing lumbar interbody fusion, 13.5% in patients treated by low-molecular-weight heparin (LMWH), while only 8.1% in patients without LMWH. However, it revealed no significant difference between LMWH group and non-LMWH group (χ2 = 1.933, p = 0.164). Logistic regression equation was logit P = −4.09 + 0.05*X1 − 0.55*X2 + 0.41*X3 + 1.41*X7, (X1 = age; X2 = regions; X3 = hypertension; X7 = D-dimer). In this study, LMWH prophylaxis after spine surgery proved ineffective. Advanced age, D-dimer and hypertension have proved to be the risk factors for postoperative DVT in patients undergoing spine surgery. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM) is characterized by the left ventricular dilatation and impaired myocardial systolic dysfunction with high mortality and morbidity. However, the underlying mechanisms remain elusive. We first identified the differentially expressed genes (DEGs) between the DCM and control group using two expression profiles from GSE3585 and GSE84796. Enrichment analysis was conducted to explore the potential mechanisms underlying DCM. A total of four algorithms, including key module of MCODE, degree, maximum neighborhood component (MNC), and maximal clique centrality (MCC), were used to identify the hub genes within Cytoscape. The correlation between hub genes and infiltrated immune cells was evaluated to determine potential immune-related genes. The expression analysis and diagnosis value analysis of potential immune-related genes were performed. Finally, the expression analysis with GSE57338 and relationship analysis with the comparative toxicogenomics database (CTD) were performed to identify the key immune-related genes in DCM. A total of 80 DEGs were screened for DCM. Enrichment analysis revealed that DEGs were involved in the immune-related pathological process. Immune infiltration analysis indicated a potentially abnormal immune response in DCM. Four up-regulated genes (COL1A2, COL3A1, CD53, and POSTN) were identified as potential immune-related genes. Finally, three genes (COL1A2, COL3A1, and POSTN) were determined as the key immune-related genes in DCM via expression analysis with a validation set (GSE57338) and relationship analysis with CTD. Our study suggested that the upregulated COL1A2, COL3A1, and POSTN might be the key immune-related genes for DCM. Further studies are needed to validate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

This study compared the differences in the clinical manifestations, treatment courses and clinical turnover between mild and moderate coronavirus disease 2019 (COVID-19). Clinical data of the patients with imported COVID-19 admitted to Beijing Xiaotangshan Designated Hospital between March 15 and April 30, 2020, were retrospectively analysed. A total of 53 COVID-19 patients were included, with 21 mild and 32 moderate cases. Compared with the mild group, the moderate group showed significant differences in breathing frequency, lymphocyte count, neutrophil percentage, neutrophil/lymphocyte ratio, procalcitonin, C-reactive protein, and dynamic erythrocyte sedimentation rate. In the moderate group, 87.5% exhibited ground-glass opacities, 14% exhibited consolidative opacities, 53.1% exhibited local lesions and 68.8% exhibited unilateral lesions. The proportion of patients who received antiviral or antibiotic treatment in the moderate group was higher than that in the mild group, and the number of cases that progressed to severe disease in the moderate group was also significantly higher (18.7% vs. 0%, p = 0.035). Compared with patients with mild COVID-19, those with moderate COVID-19 exhibited more noticeable inflammatory reactions, more severe pulmonary imaging manifestations and earlier expression of protective antibodies. The overall turnover of the moderate cases was poorer than that of the mild cases. [ABSTRACT FROM AUTHOR]

In lime concretion black soil, a two-factor (tillage and irrigation) split block experiment from 2015 to 2017 was conducted to identify whether their combination is suitable for the improvement of winter wheat yield and water use efficiency. The main treatments were subsoiling (SS) and rotary tillage (RT), with secondary treatments of three irrigation regimes: no irrigation during the whole growth period (W0), irrigation at jointing stage (W1), and irrigation at both jointing and anthesis stages (W2). In combination with a soil column experiment, the contribution of the root system in different soil layers to yield was clarified. The results indicated that both tillage and irrigation significantly influenced the spatiotemporal distributions of the root systems and yield components, while tillage produced the strongest effect. Compared with RT, SS significantly promoted the root penetration and delayed root senescence in deep soil layers. With increasing soil depth, each root configuration parameter (dry root weight density, DRWD; root length density, RLD; root surface area per unit area, RSA; root volume per unit area, RV) gradually decreased, and the peak appearance times of each root parameter in RT and three parameters (RLD, RSA and RV) in SS were postponed from heading to anthesis and from anthesis to filling stage, respectively. The average post-peak attenuation values at soil layers from 60 to 100 cm in W1 were less than those in W0 and W2. SSW1 generated the highest grain yields, with an average increase of 31.88% compared with the yield in RTW0. Root systems at three soil layers (0–40 cm, 40–80 cm and below 80 cm) differentially contributed to grain yields with 78.32%, 12.09% and 9.59%, respectively. The growth peak of the deep root system in SSW1 was postponed to the filling stage, and the post-peak attenuation declining rates were also slowed. Therefore, SSW1 is an effective cultivation method improving grain yields and water use efficiency in lime concretion black soil. [ABSTRACT FROM AUTHOR]

Internet addiction (IA) is common among adolescents and significantly determined by sociocultural and economic factors. The aim of this study was to compare the prevalence of IA among adolescents between Macau and mainland China and also examine its association with quality of life. A total of 2892 secondary school students were included. Standardized instruments were used to measure IA, depressive symptoms and quality of life. The overall prevalence of IA was 23.7%, with 32.5% in Macau and 19.8% in mainland China. Students in Macau were more likely to suffer from IA than those in mainland China (OR = 2.15, p < 0.001). Correlates of IA included being in higher school grades, poor academic performance, and more severe depressive symptoms. Students with IA reported lower quality of life in physical, psychological, social, and environmental domains. IA is common among Chinese adolescents, particularly in Macau. Considering the negative impact of IA on health and quality of life, regular screening and effective interventions should be undertaken for young Internet users. [ABSTRACT FROM AUTHOR]

These authors contributed equally: Feng Li, Tong-Yue Du and Li-Da Wu. Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-022-26277-w, published online 01 February 2023 The original version of this Article contained an error in the order of the author names, which was incorrectly given as Feng Li, Tong-Yue Du, Li-Da Wu, Lei Zhang, Huan-Huan Liu, Zhen-Ye Zhang, Jie Zhang, Zhi-Yuan Zhang, Ling-Ling Qian, Jian-Feng Hao & Ru-Xing Wang. [Extracted from the article]

Chemotherapy and radiotherapy predominantly improve the clinical outcomes of patients with human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC). Whether this superiority goes on when treated with immune checkpoint inhibitors is still unclear. This study sought to determine the predictive value and potential mechanisms of HPV status for the treatment of programmed cell death 1 (PD-1)/ligand 1(PD-L1) inhibitors. We conducted an integrated analysis of the relationships between HPV status and PD-L1, tumor mutation burden (TMB) and inflammation-related immune cells and molecules, based on the analysis of repository databases and resected HNSCC specimens. The pooled analysis of overall survival (OS) and objective response rate (ORR) suggested that HPV-positive patients benefited more from PD-1/PD-L1 inhibitors than HPV-negative patients (OS: hazard ratio (HR) = 0.71, p = 0.02; ORR: 21.9% vs 14.1%, odds ratio (OR) = 1.79, p = 0.01). Analysis of public databases and resected HNSCC specimens revealed that HPV status was independent of PD-L1 expression and TMB in HNSCC. However, HPV infection significantly increased T-cell infiltration, immune effector cell activation and the diversity of T-cell receptors. Notably, HPV-positivity correlated with increased immune cytolytic activity and a T-cell-inflamed gene expression profile. This work provides evidence that HPV status can be used to predict the effectiveness of PD-1 inhibitors in HNSCC, independently of PD-L1 expression and TMB, and probably results from an inflamed immune microenvironment induced by HPV infection. [ABSTRACT FROM AUTHOR]

Plant subtilases (SBTs) are a widely distributed family of serine proteases which participates in plant developmental processes and immune responses. Although SBTs are divided into seven subgroups in plants, their origin and evolution, particularly in green algae remain elusive. Here, we present a comprehensive large-scale evolutionary analysis of all subtilases. The plant subtilases SBT1-5 were found to be monophyletic, nested within a larger radiation of bacteria suggesting that they originated from bacteria by a single horizontal gene transfer (HGT) event. A group of bacterial subtilases comprising representatives from four phyla was identified as a sister group to SBT1-5. The phylogenetic analyses, based on evaluation of novel streptophyte algal genomes, suggested that the recipient of the HGT of bacterial subtilases was the common ancestor of Coleochaetophyceae, Zygnematophyceae and embryophytes. Following the HGT, the subtilase gene duplicated in the common ancestor and the two genes diversified into SBT2 and SBT1, 3–5 respectively. Comparative structural analysis of homology-modeled SBT2 proteins also showed their conservation from bacteria to embryophytes. Our study provides the first molecular evidence about the evolution of plant subtilases via HGT followed by a first gene duplication in the common ancestor of Coleochaetophyceae, Zygnematophyceae, and embryophytes, and subsequent expansion in embryophytes. [ABSTRACT FROM AUTHOR]

This research presents the first experimental observation of the enhancement of the polarization Coulomb field (PCF) scattering by aggressive lateral scaling of GaN HEMTs. By decreasing the source-drain distance to 300 nm through n+-GaN ohmic regrowth, 70-nm gate AlGaN/GaN HEMTs achieved an extremely low electron mobility. Different from the electron mobility of the traditional device, which was determined by polar optical phonon scattering, the electron mobility of the 70-nm gate AlGaN/GaN HEMTs was dominated by PCF scattering due to the enhanced nonuniform strain distribution of the AlGaN barrier layer. Furthermore, compared with the parasitic access resistance at gate-source voltage VGS = 0 V, the parasitic access resistance at VGS = −2.5 V showed an increase of approximately 700%, which was also responsible for the enhanced PCF scattering. [ABSTRACT FROM AUTHOR]

Microorganism degradation is efficient to remove the steroid hormones like 17β-estradiol (E2); but their degradation mechanism and metabolic network to these chemicals are still not very clear. Here the global responses of the estrogen-degradation strain Pseudomonas putida SJTE-1 to 17β-estradiol and glucose were analyzed and compared using the iTRAQ (isobaric tags for relative and absolute quantization) strategy combined with LC-MS/MS (liquid chromatography-tandem mass spectrometry). 78 proteins were identified with significant changes in expression; 45 proteins and 33 proteins were up-regulated and down-regulated, respectively. These proteins were mainly involved in the processes of stress response, energy metabolism, transportation, chemotaxis and cell motility, and carbon metabolism, considered probably responding to 17β-estradiol and playing a role in its metabolism. The up-regulated proteins in electron transfer, energy generation and transport systems were thought crucial for efficient uptake, translocation and transformation of 17β-estradiol. The over-expression of carbon metabolism proteins indicated cells may activate related pathway members to utilize 17β-estradiol. Meanwhile, proteins functioning in glucose capture and metabolism were mostly down-regulated. These findings provide important clues to reveal the 17β-estradiol degradation mechanism in P. putida and promote its bioremediation applications. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate whether folic acid supplementation would improve cognitive performance by reducing serum inflammatory cytokine concentrations. This RCT was performed in Tianjin, China. Participants with mild cognitive impairment (MCI) were randomly assigned to the folic acid (400 μg/day) or conventional treatment groups. Neuropsychological tests were administered, and folate, homocysteine, vitamin B12, IL-6, TNF-α, Aβ-42, and Aβ-40 were measured at baseline and at 6- and 12-month time points.152 participants (folic acid: 77, conventional: 75) completed the trial. Significant improvements in folate (ηp2 = 0.703, P = 0.011), homocysteine (ηp2 = 0.644, P = 0.009), Aβ-42 (ηp2 = 0.687, P = 0.013), peripheral IL-6 (ηp2 = 0.477, P = 0.025), TNF-α (ηp2 = 0.709, P = 0.009) levels were observed in folic acid group compared with conventional group. Folic acid supplementation improved the Full Scale Intelligence Quotient (P = 0.028; effect size d = 0.153), Information (P = 0.031; d = 0.157) and Digit Span (P = 0.009; d = 0.172) scores at 12 months compared with conventional treatment. Based on these findings, daily oral administration of a 400-μg folic acid supplement to MCI subjects for 12 months can significantly improve cognitive performance and reduce peripheral inflammatory cytokine levels. [ABSTRACT FROM AUTHOR]

The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway has been identified as an important pathway in renal cell carcinoma (RCC). We have reported a nonsense mutation in PIK3R1, which encodes the regulatory subunit of PI3K, in a metastatic RCC (mRCC), while the mutation was absent in the corresponding primary RCC (pRCC). To identify the function of PIK3R1 in RCC, we examined its expression in normal kidney, pRCC and mRCC by immunohistochemistry and real-time polymerase chain reaction. The expression of PIK3R1 significantly decreased in pRCC and was further reduced in mRCC compared with normal tissue. Besides, its expression levels were negatively correlated with T-category of tumor stage. Additionally, 786-O and A-704 cells with PIK3R1 depletion introduced by CRISPR/Cas9 system displayed enhanced proliferation, migration and epithelial-mesenchymal transition (EMT), and acquired a stem-like phenotype. Moreover, the PIK3R1 depletion promoted the phosphorylation of AKT in the cells. The knockdown of AKT by shRNA reduced p-GSK3β and CTNNB1 expression in the cells, while the depletion of CTNNB1 impaired stem-like phenotype of the cells. Overall, PIK3R1 down-regulation in RCC promotes propagation, migration, EMT and stem-like phenotype in renal cancer cells through the AKT/GSK3β/CTNNB1 pathway, and may contribute to progression and metastasis of RCC. [ABSTRACT FROM AUTHOR]