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Climate change and human activities affect the biomass of different algal and the succession of dominant species. In the past, phytoplankton phyla inversion has been focused on oceanic and continental shelf waters, while phytoplankton phyla inversion in inland lakes and reservoirs is still in the initial and exploratory stage, and the research results are relatively few. Especially for mid-to-high latitude lakes, the research is even more blank. Therefore, this study proposes a machine learning method based on OLCI/Sentinel-3 satellite imagery to retrieve algal biomass abundance. Remote sensing models were developed to estimate the biomass abundance of three major algal groups: Cyanophyta, Chlorophyta, and Bacillariophyta. This study compared and evaluated 6 commonly used machine learning models, including extreme gradient boosting (XGBoost), support vector regression (SVR), backpropagation neural network (BP), gradient boosting decision tree (GBDT), random forest (RF), and categorical boosting (CatBoost). The results indicated that XGBoost exhibited the highest accuracy (R 2  = 0.92, RMSE = 1.78%, MAPE = 9.96%) in estimating Cyanophyta's biomass abundance. The RF model demonstrated the highest accuracy for estimating Chlorophyta's biomass abundance (R 2  = 0.72, RMSE = 6.57%, MAPE = 50.8%), while the GBDT model exhibited the highest accuracy for estimating Bacillariophyta's biomass abundance (R 2  = 0.9, RMSE = 4.66%, MAPE = 47.87%). The models were subsequently applied to all cloud-free OLCI images from Hulun Lake during the ice-free periods from 2016 to 2023, producing spatiotemporal distribution maps of the different phytoplankton biomass abundance. Cyanophyta dominated the biomass abundance (44.62 ± 3.47%), followed by Bacillariophyta (36.35 ± 2.68%), and Chlorophyta had the lowest proportion (10.42 ± 1.08%). Together, these three algae groups constituted 91.4 ± 1.55% of all phytoplankton in Hulun Lake. Significant annual variations in the biomass abundance of Cyanophyta and Bacillariophyta were observed, whereas those of Chlorophyta remained stable. Additionally, this study examined the effects of climatic factors and water quality parameters on the biomass abundance of algae. The findings suggest that temperature, wind speed, and atmospheric pressure are critical factors influencing the biomass abundance of the different algae groups. This study not only fills the gaps in the related field, but also provides a new method for monitoring algae, as well as a strong support for realizing the goals of sustainable management of water resources and ecological protection., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Cancer is one of the leading causes of morbidity and mortality in the global population. The effective management of cancer-associated pain and anesthesia are critical aspects of comprehensive cancer treatment. However, the role and mechanism of anesthesia and analgesia-related drugs in tumors remain controversial. In this study, the efficacy of 16 commonly used analgesics and anesthetics against non-small cell lung cancer (NSCLC) was evaluated. Among the 16 examined injections, butorphanol tartrate injection significantly inhibited the proliferation of NSCLC cells and increased the sensitivity of the EGFR-TKI-resistant H1975 cell line to gefitinib. Benzethonium chloride (BC) is the main active antitumor ingredient of butorphanol tartrate injection. BC may regulate the cell cycle, apoptosis and EMT signaling pathways by modulating the P53 signaling pathway. Our study reveals the therapeutic value of butorphanol tartrate injection and BC in the treatment of NSCLC and provides a theoretical basis for comprehensive therapies for NSCLC., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests. Ethical approval and consent to participate: All animal experiments were approved by the Animal Ethics Committee of the Zhejiang Academy of Traditional Chinese Medicine and were conducted according to the Guidelines for the Care and Use of Animals for Scientific Research. Consent for publication: The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).)

Objective: To investigate the association between coal dust exposure and the occurrence of dyslipidemia in coal mine workers, and identify relevant risk factors. Methods: We selected a population who underwent occupational health examinations at Huainan Yangguang Xinkang Hospital from March 2020 to July 2022. Participants were divided into two groups based on the presence or absence of dyslipidemia, and their baseline information was collected, including records of coal dust exposure. We employed single-factor analysis to identify risk factors for dyslipidemia and adjusted for confounding factors in the adjusted models. Additionally, we explored the effects in different populations using stratified analysis, smooth curve fitting, and propensity score matching. Finally, we confirmed the causal relationship between coal dust exposure and dyslipidemia by examining tissue sections and lipid-related indicators in a mouse model of coal dust exposure. Results A total of 5,657 workers were included in the study, among whom 924 individuals had dyslipidemia and 4,743 individuals did not have dyslipidemia. The results of the single-factor analysis revealed that dust exposure, age, BMI, blood pressure, and smoking were statistically significant risk factors for dyslipidemia (p < 0.05). Additionally, the three multivariate models, adjusted for different confounders, consistently showed a significant increase in the risk of dyslipidemia associated with coal dust exposure (Model 1: OR, 1.869; Model 2: OR, 1.863; Model 3: OR, 2.033). After conducting stratified analysis, this positive correlation remained significant. Furthermore, propensity score matching analysis revealed that with increasing years of work, the risk of dyslipidemia gradually increased, reaching 50% at 11 years. In the mouse model of coal dust exposure, significant coal dust deposition was observed in the lungs and livers of the mice, accompanied by elevated levels of total cholesterol (TC), alanine transaminase (ALT), aspartate transaminase (AST), and low-density lipoprotein cholesterol (LDL-C). Conclusion Exposure to coal dust significantly increases the risk of developing dyslipidemia, and this positive correlation exists in different populations, particularly with increasing years of work, resulting in a higher risk., (© 2024. The Author(s).)

This research explores the feasibility of using a nanocomposite from multi-walled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) for thermal engineering applications. The hybrid nanocomposites were suspended in water at various volumetric concentrations. Their heat transfer and pressure drop characteristics were analyzed using computational fluid dynamics and artificial neural network models. The study examined flow regimes with Reynolds numbers between 5000 and 17,000, inlet fluid temperatures ranging from 293.15 to 333.15 K, and concentrations from 0.01 to 0.2% by volume. The numerical results were validated against empirical correlations for heat transfer coefficient and pressure drop, showing an acceptable average error. The findings revealed that the heat transfer coefficient and pressure drop increased significantly with higher inlet temperatures and concentrations, achieving approximately 45.22% and 452.90%, respectively. These results suggested that MWCNTs-GNPs nanocomposites hold promise for enhancing the performance of thermal systems, offering a potential pathway for developing and optimizing advanced thermal engineering solutions., (© 2024. The Author(s).)

Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have been shown to promote angiogenesis after ischemic stroke, in which microRNAs (miRs) are believed to play an important role in exosome-mediated therapeutic effects, though the mechanism is still not clear. In this study, a series of molecular biological and cellular assays, both in vitro and in vivo, were performed to elucidate the role of exosomal miR-486 in angiogenesis following cerebral ischemic and its molecular mechanisms. Our results revealed that BMSC-Exos significantly improved neurological function and increased microvessel density in ischemic stroke rats. In vitro assays showed that BMSC-Exos promoted the proliferation, migration, and tube formation ability of oxygen-glucose deprivation/reoxygenation (OGD/R) injured rat brain microvascular endothelial cells (RBMECs). Importantly, BMSC-Exos increased the expression of miR-486 and phosphorylated protein kinase B (p-Akt) and down-regulated the protein level of phosphatase and tensin homolog (PTEN) in vivo and in vitro. Mechanistic studies demonstrated that transfection with miR-486 mimic enhanced RBMECs angiogenesis and increased p-Akt expression, while inhibited PTEN expression. On the other hand, the miR-486 inhibitor induced an opposite effect, which could be blocked by PTEN siRNA. It was thus concluded that exosomal miR-486 from BMSCs may enhance the functional recovery by promoting angiogenesis following cerebral ischemic injury, which might be related to its regulation of the PTEN/Akt pathway., (© 2024. The Author(s).)

A comprehensive emergency medical service (EMS) system significantly enhances a city's capacity to prevent and mitigate disasters. Using Huangshi as a case study, this research evaluated the service radium coverage rate of the current EMS system by examining its transport capacity, population density, and prevalence rate, finding it to be only 61.49% with an inefficient spatial layout. To address this, we proposed transforming urban brownfields into EMS parks. By selecting the most suitable brownfields based on capacity and service radius, we increased the coverage rate to 90.21%. We introduced a new "consultation-referral" model, where existing EMS facilities serve as pre-diagnosis and triage centers, and the urban brownfield EMS parks function as isolation and centralized treatment centers. GIS network analysis confirmed the feasibility, showing all transit times to be under 30 min. The methodology outlined in this study-comprising "demand assessment, supply optimization, and feasibility verification"-not only strengthens the city's EMS system but also facilitates the renewal of urban brownfields. This approach can serve as a valuable reference for enhancing EMS systems in other cities., (© 2024. The Author(s).)

The Dai people are primarily found in Yunnan Province, China, and have a long heritage there. The latest national census reports that Yunnan is home to 1,259,000 individuals of the Dai ethnic group. This study focuses on 3504 Dai settlements in Yunnan, identified through county records. Using the ArcGIS spatial analysis platform, we first evaluated their settlements' spatial distribution patterns using metrics like the nearest neighbor index and geographic concentration index. Then, we applied geodetector to investigate the underlying mechanisms of their distribution. The results reveal that: (1) Dai settlements in Yunnan Province generally have a cohesive spatial distribution; at the provincial level, however, there is an uneven distribution pattern, with many densely populated areas and a pattern of "two cores, one belt, one area, and two points"; (2) The Dai settlements predominantly occupy the third gradient of the vertical zonation, with Dai gathering settlements primarily found in the Lancang, Ayeyarwaddy, and Red River basins. Conversely, Dai mixed settlements are mainly situated in the Lancang, Red, and Nu River basins; (3) Analysis via geodetector indicates that ethnocultural factors are the most significant in determining the spatial distribution of the Dai settlements, followed by socio-economic and natural factors; (4) The distribution of settlements is significantly influenced by the proportion of the Dai population within these settlements. Dai gathering settlements are typically located on flat slopes with elevations ranging from 500 to 1000 m and slopes of 0°-5°. Meanwhile, Dai mixed settlements are found on gentle slopes with elevations of 1000-2000 m and slopes of 5°-15°. The study reveals that the location of Dai settlements is strongly influenced by environmental considerations and has a significant explanation from similar origins., (© 2024. The Author(s).)

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients., (© 2024. The Author(s).)

The intensification of heatwaves dues to climate change is a significant concern, with substantial impacts on ecosystems and human health, particularly in developing countries. This study utilizes NASA Earth Exchange Global Daily Downscaled Projections (NEX-GDDP-CMIP6) and projected population data accounting for China's population policies to project changes in various grades of heatwaves (light, moderate, and severe) and the population exposure to heatwaves (PEH) in Xinjiang under three shared socioeconomic pathways (SSP1-2.6, SSP2-4.5, and SSP5-8.5). The results show that the number of days and intensity of heatwaves in Xinjiang are projected to increase. Heatwaves occurring in Xinjiang will predominantly be severe heatwaves (SHW) in the long-term under the SSP5-8.5 scenario, and the number of SHW days projected to increase by 62 ± 18.4 days compared to the reference period. Changes in heatwaves are anticipated to influence PEH, estimating population exposure to light, moderate, and severe heatwaves (LPEH, MPEH, and SPEH) at 534.6 ± 64 million, 496.2 ± 43.5 million, and 1602.4 ± 562.5 million person-days, respectively, in the long-term under the SSP5-8.5 scenario. The spatial distribution of PEH is projected to be consistent with that of the reference period, with high values persisting in Urumqi, Kashgar and Hotan. Changes in PEH are primarily driven by climate effects, followed by interactive effects, while population effects contribute the least. Therefore, mitigating climate change is crucial to reduce the PEH in Xinjiang., (© 2024. The Author(s).)

To investigate the influence of a geogrid-reinforced tailings dam on the seepage stability of the dam body, this paper was based on the field test of a reinforced tailings accumulation dam. The study utilized the finite element strength reduction method to simulate the stability of the main dam of the Fengshuigou tailings reservoir under different seepage conditions using ABAQUS software. Additionally, the paper discussed the impact of conventional heightening, dry beach length, and geogrid reinforcement on the position and safety factor of the saturation line of the dam body. The results showed that when the dam body was raised, the saturation line rose by 2.8-5.3 m, resulting in a decrease in the safety factor. The geogrid effectively reduced the height of the saturation line in the tailings dam. In comparison to the unreinforced condition (dam heightening), the saturation line of the tailings dam decreased by 0.9-2.8 m under the local reinforcement condition and by 3.2-12.5 m under the overall reinforcement condition. The geogrid significantly improved the stability of the tailings dam. Furthermore, under the local reinforcement condition, the safety factor of the dam increased by 3.8-5.5%, and under the overall reinforcement condition, it increased by 35.9-42.9%, when compared to the unreinforced condition. Increasing the dry beach length improved the stability of the tailings dam, and under normal working conditions, the safety of the tailings dam was much higher than under the minimum dry beach condition. These results served as a reference for the design of the dam and the new tailings reservoir, laying a foundation for the sustainable development and environmental protection of the tailings pond., (© 2024. The Author(s).)

In patients with unresectable non-small cell lung cancer, histological diagnosis is frequently based on small biopsy specimens unsuitable for histological diagnosis when they are severely crushed and do not retain their morphology. Therefore, establishing a novel diagnostic method independent of tissue morphology or conventional immunohistochemistry (IHC) markers is required. We analyzed the lipid profiles of resected primary lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) specimens using liquid chromatography-tandem mass spectrometry. The specimens of 26 ADC and 18 SQCC cases were evenly assigned to the discovery and validation cohorts. Non-target screening on the discovery cohort identified 96 and 13 lipid peaks abundant in ADC and SQCC, respectively. Among these 109 lipid peaks, six and six lipid peaks in ADC and SQCC showed reproducibility in target screening on the validation cohort. Finally, we selected three and four positive lipid markers for ADC and SQCC, demonstrating high discrimination abilities. In cases difficult to diagnose by IHC staining, [cardiolipin(18:2&#95;18:2&#95;18:2&#95;18:2)-H] - and [triglyceride(18:1&#95;17:1&#95;18:1) + NH4] + showed the excellent diagnostic ability for ADC (sensitivity: 1.00, specificity: 0.89, accuracy: 0.93) and SQCC (sensitivity: 0.89, specificity: 0.83, accuracy: 0.87), respectively. These novel candidate lipid markers may contribute to a more accurate diagnosis and subsequent treatment strategy for unresectable NSCLC., (© 2023. The Author(s).)

Heatwaves have pronounced impacts on human health and the environment on a global scale. Although the characteristics of heatwaves has been well documented, there still remains a lack of dynamic studies of population exposure to heatwaves (PEH), particularly in the arid regions. In this study, we analyzed the spatio-temporal evolution characteristics of heatwaves and PEH in Xinjiang using the daily maximum temperature (T max ), relative humidity (RH), and high-resolution gridded population datasets. The results revealed that the heatwaves in Xinjiang occur more continually and intensely from 1961 to 2020. Furthermore, there is substantial spatial heterogeneity of heatwaves with eastern part of the Tarim Basin, Turpan, and Hami been the most prone areas. The PEH in Xinjiang showed an increasing trend with high areas mainly in Kashgar, Aksu, Turpan, and Hotan. The increase in PEH is mainly contributed from population growth, climate change and their interaction. From 2001 to 2020, the climate effect contribution decreased by 8.5%, the contribution rate of population and interaction effects increased by 3.3% and 5.2%, respectively. This work provides a scientific basis for the development of policies to improve the resilience against hazards in arid regions., (© 2023. The Author(s).)

Covalent and non-covalent nanofluids were tested inside a circular tube fitted with twisted tape inserts with 45° and 90° helix angles. Reynolds number was 7000 ≤ Re ≤ 17,000, and thermophysical properties were assessed at 308 K. The physical model was solved numerically via a two-equation eddy-viscosity model (SST k-omega turbulence). GNPs-SDBS@DW and GNPs-COOH@DW nanofluids with concentrations (0.025 wt.%, 0.05 wt.% and 0.1 wt.%) were considered in this study. The twisted pipes' walls were heated under a constant temperature of 330 K. The current study considered six parameters: outlet temperature, heat transfer coefficient, average Nusselt number, friction factor, pressure loss, and performance evaluation criterion. In both cases (45° and 90° helix angles), GNPs-SDBS@DW nanofluids presented higher thermohydraulic performance than GNPs-COOH@DW and increased by increasing the mass fractions such as 1.17 for 0.025 wt.%, 1.19 for 0.05 wt.% and 1.26 for 0.1 wt.%. Meanwhile, in both cases (45° and 90° helix angles), the value of thermohydraulic performance using GNPs-COOH@DW was 1.02 for 0.025 wt.%, 1.05 for 0.05 wt.% and 1.02 for 0.1 wt.%., (© 2022. The Author(s).)

The hydraulic performance of single-wing labyrinth drip irrigation tapes under the coupling effect of water and fertilizer affects the operating efficiency of the entire drip irrigation system. In this study, three types of single-wing labyrinth drip irrigation tapes were studied. We evaluated the average relative flow of each type and conducted indoor uniform orthogonal tests of three factors, namely, fertilizer concentration, sediment content, and operating pressure. The results showed that the order of the factors affecting the average relative flow of single-wing labyrinth drip irrigation tape was sediment content > fertilizer concentration > operating pressure. The projection pursuit regression (PPR) models of the average relative flow of three types of single-wing labyrinth drip irrigation tapes (H1, H2, and H3) were established. The root mean square errors (nRMSE) of these three models were 0.66%, 0.74%, 0.34%, respectively, indicating their excellent prediction performance. The optimal performance of the three types of tapes were obtained when the fertilizer concentration was 0.6 g/L, the sediment content was 1 g/L, and the operating pressure was 40 kPa. Under the optimal condition, the average relative flows of H1-type, H2-type, and H3-type were 0.792, 0.764, and 0.700, respectively., (© 2022. The Author(s).)

The efficacies of pembrolizumab and nivolumab have never been directly compared in a real-world study. Therefore, we sought to retrospectively evaluate the objective response rate (ORR) and the progression-free survival (PFS) of patients with recurrent or advanced non-small cell lung cancer (NSCLC) in a real-world setting. This study included patients with recurrent or advanced NSCLC diagnosed between September 1, 2015 and August 31, 2019, who were treated with programmed cell death 1 (PD-1) inhibitors at the Cancer Center of the Chinese People's Liberation Army. PFS was estimated for each treatment group using Kaplan-Meier curves and log-rank tests. The multivariate analysis of PFS was performed with Cox proportional hazards regression models. A total of 255 patients with advanced or recurrent NSCLC treated with PD-1 inhibitors were identified. The ORR was significantly higher in the pembrolizumab group than in the nivolumab group, while PFS was not significantly different between the two groups. Subgroup analysis showed that the ORR was significantly higher for pembrolizumab than for nivolumab in patients in the first-line therapy subgroup and in those in the combination therapy as first-line therapy subgroup. Survival analysis of patients receiving combination therapy as second- or further-line therapy showed that nivolumab had better efficacy than pembrolizumab. However, the multivariate analysis revealed no significant difference in PFS between patients treated with pembrolizumab and those treated with nivolumab regardless of the subgroup. In our study, no significant difference in PFS was noted between patients treated with pembrolizumab and those treated with nivolumab in various clinical settings. This supports the current practice of choosing either pembrolizumab or nivolumab based on patient preferences.

Retinoic acid-related orphan receptor gamma (RORγ) plays pivotal roles in autoimmune diseases by controlling the lineage of interleukin 17 (IL-17)-producing CD4 + T cells (Th17 cells). Structure-based drug design has proven fruitful in the development of inhibitors targeting the ligand binding domain (LBD) of RORγ. Here, we present the crystal structure of a novel RORγ inhibitor co-complex, in the presence of a corepressor (CoR) peptide. This ternary complex with compound T reveals the structural basis for an inhibitory mechanism different from the previously reported inverse agonist. Compared to the inverse agonist, compound T induces about 2 Å shift of helix 5 (H5) backbone and side-chain conformational changes of Met365 on H5. These conformational changes correlate to reduced CoR peptide binding to RORγ-LBD in the presence of compound T, which suggests that the shift of H5 is responsible. This crystal structure analysis will provide useful information for the development of novel and efficacious drugs for autoimmune disorders.

Comparative population genomics analysis is an effective approach to identify selection signatures in farm animals. In this study, we systematically investigated the selection signatures in six phenotypically diverse goat breeds using SNPs obtained from pooled whole-genome resequencing data. More than 95.5% of 446-642 million clean reads were mapped to the latest reference goat genome, which generated a sequencing depth ranging from 22.30 to 31.75-fold for each breed. A total of 5,802,307, 6,794,020, 7,562,312, 5,325,119, 8,764,136, and 9,488,057 putative SNPs were detected in Boer, Meigu, Jintang Black, Nanjiang Yellow, Tibetan, and Tibetan cashmere goats, respectively. Based on the genome-wide F ST and expected heterozygosity scores along 100-kb sliding windows, 68, 89, 44, 44, 19, and 35 outlier windows were deemed as the selection signatures in the six goat breeds. After genome annotation, several genes within the selection signals were found to be possibly associated with important traits in goats, such as coat color (IRF4, EXOC2, RALY, EIF2S2, and KITLG), high-altitude adaptation (EPAS1), growth (LDB2), and reproduction traits (KHDRBS2). In summary, we provide an improved understanding of the genetic diversity and the genomic footprints under positive selection or the adaptations to the local environments in the domestic goat genome.

Warfarin is the most recommended anticoagulant drug for patients undergoing heart valve replacement. However, due to the narrow therapeutic window and individual dose, the use of warfarin needs more advanced technology. We used the data collected from a multi-central registered clinical system all over China about the patients who have undergone heart valve replacement, subsequently divided into three groups (training group: 10673 cases; internal validation group: 3558 cases; external validation group: 1463 cases) in order to construct a hybrid model with genetic algorithm and Back-Propagation neural network (BP-GA), For testing the model's prediction accuracy, we used Mean absolute error (MAE), Root mean squared error (RMSE) and the ideal predicted percentage of total and dose subgroups. In results, whether in internal or in external validation group, the total ideal predicted percentage was over 58% while the intermediate dose subgroup manifested the best. Moreover, it showed higher prediction accuracy, lower MAE value and lower RMSE value in the external validation group than that in the internal validation group (p < 0.05). In conclusion, BP-GA model is promising to predict warfarin maintenance dose.

Silkworms (Bombyx mori) reared on artificial diets have great potential applications in sericulture. However, the mechanisms underlying the enhancement of metabolic utilization by altering silkworm nutrition are unclear. The aim of this study was to investigate the mechanisms responsible for the poor development and low silk protein synthesis efficiency of silkworms fed artificial diets. After multi-generational selection of the ingestive behavior of silkworms to artificial diets, we obtained two strains, one of which developed well and another in which almost all its larvae starved to death on the artificial diets. Subsequently, we analyzed the metabolomics of larval hemolymph by gas chromatography/liquid chromatography-mass spectrometry, and the results showed that vitamins were in critically short supply, whereas the nitrogen metabolic end product of urea and uric acid were enriched substantially, in the hemolymph of the silkworms reared on the artificial diets. Meanwhile, amino acid metabolic disorders, as well as downregulation of carbohydrate metabolism, energy metabolism, and lipid metabolism, co-occurred. Furthermore, 10 male-dominant metabolites and 27 diet-related metabolites that differed between male and female silkworms were identified. These findings provide important insights into the regulation of silkworm metabolism and silk protein synthesis when silkworms adapt to an artificial diet.

Developing an alternative method for fabricating microscale graphene patterns that overcomes the obstacles of organic contamination, linewidth resolution, and substrate damaging is paramount for applications in optoelectronics. Here we propose to pattern chemical vapor deposition grown graphene film through a stencil mask by magnetic-assisted ultraviolet (UV) ozonation under irradiation of a xenon excimer lamp. In this process, the paramagnetic oxygen molecules and photochemically generated oxygen radicals are magnetized and attracted in an inhomogenous external magnetic field. As a consequence, their random motions convert into directional, which can greatly modify or enhance the quality of graphene patterns. Using a ferromagnetic steel mask, an approximately vertical magnetic-field-assisted UV ozonation (B Z  = 0.31 T, ∇B Z  = 90 T · m -1 ) has a capability of patterning graphene microstructures with a line width of 29 μm and lateral under-oxidation less than 4 μm. Our approach is applicable to patterning graphene field-effect transistor arrays, and it can be a promising solution toward resist-free, substrate non-damaging, and cost effective microscale patterning of graphene film.

Abnormalities in the circadian clock system are known to affect the body's metabolic functions, though the molecular mechanisms responsible remain uncertain. In this study, we achieved continuous knockdown of B. mori Period (BmPer) gene expression in the B. mori ovary cell line (BmN), and generated a Per-KD B. mori model with developmental disorders including small individual cells and slow growth. We conducted cell metabolomics assays by gas chromatography/liquid chromatography-mass spectrometry and showed that knockdown of BmPer gene expression resulted in significant inhibition of glycometabolism. Amino acids that used glucose metabolites as a source were also down-regulated, while lipid metabolism and nucleotide metabolism were significantly up-regulated. Metabolite correlation analysis showed that pyruvate and lactate were closely related to glycometabolism, as well as to metabolites such as aspartate, alanine, and xanthine in other pathways. Further validation experiments showed that the activities of the key enzymes of glucose metabolism, hexokinase, phosphofructokinase, and citrate synthase, were significantly decreased and transcription of their encoding genes, as well as that of pyruvate kinase, were also significantly down-regulated. We concluded that inhibition of the circadian clock gene BmPer repressed glycometabolism, and may be associated with changes in cellular amino acid metabolism, and in cell growth and development.

The prevalence of cardiac malignant neoplasms in the general population has been shown to be significant higher than what was previously estimated, yet their treatment has remained difficult and effective therapies are lacking. In the current study, we developed a novel thermotherapy in which PEG-functionalized carbon nanotubes were injected into the tumor regions to assist in the targeted delivery of infrared radiation energy with minimal hyperthermic damage to the surrounding normal tissues. In a mouse model of cardiac malignant neoplasms, the injected carbon nanotubes could rapidly induce coagulative necrosis of tumor tissues when exposed to infrared irradiation. In accordance, the treatment was also found to result in a restoration of heart functions and a concomitant increase of survival rate in mice. Taken together, our carbon nanotube-based thermotherapy successfully addressed the difficulty facing conventional laser ablation methods with regard to off-target thermal injury, and could pave the way for the development of more effective therapies against cardiac malignant neoplasms.

Carbon coated TiO 2 (TiO 2 @C) is fabricated by a convenient and green one-pot solvothermal method, in which ethylene glycol serve as both the reaction medium and carbon source without the addition of any other carbon additives. During the solvothermal process, ethylene glycol polymerize and coordinate with Ti 4+ to form the polymeric ligand precursor, then the polymer brushes carbonize and convert to homogeneous carbon layer firmly anchored on the TiO 2 nanoparticles (~1 nm thickness). The polymerization and carbonization process of the ethylene glycol is confirmed by FT-IR, Raman, TG and TEM characterizations. Benefiting from the well-dispersed nanoparticles and uniform carbon coating, the as-prepared TiO 2 @C demonstrate a high reversible capacity of 317 mAh g -1 (94.6% of theoretical value), remarkable rate capability of 125 mAh g -1 at 3.2 A g -1 and superior cycling stability over 500 cycles, possibly being one of the highest capacities reported for TiO 2 .

Bicuspid aortic valve (BAV) is the most common congenital heart disease. The current study aims to construct a diagnostic model based on metabolic profiling as a non-invasive tool for BAV screening. Blood serum samples were prepared from an estimation group and a validation group, each consisting of 30 BAV patients and 20 healthy individuals, and analyzed by liquid chromatography-mass spectrometry (LC-MS). In total, 2213 metabolites were detected and 41 were considered different. A model for predicting BAV in the estimation group was constructed using the concentration levels of monoglyceride (MG) (18:2) and glycerophospho-N-oleoyl ethanolamine (GNOE). A novel model named Zhongshan (ZS) was developed to amplify the association between BAV and the two metabolites. The area under curve (AUC) of ZS for BAV prediction was 0.900 (0.782-0.967) and was superior to all single-metabolite models when applied to the estimation group. Using optimized cutoff (-0.1634), ZS model had a sensitivity score of 76.7%, specificity score of 90.0%, positive predictive value of 80% and negative predictive value of 85.0% for the validation group. These results support the use of serum-based metabolomics profiling method as a complementary tool for BAV screening in large populations.

Previous studies have observed reduced suppression of the default mode network (DMN) during cognitive tasks in schizophrenia, suggesting inefficient DMN suppression is critical for the cognitive deficits of schizophrenia. Cognitive function in schizophrenia patients, however, varies from relatively intact to severely impaired. This study, which compared the DMN suppression patterns between first-episode schizophrenia patients with (SZ-Imp) and without (SZ-Pre) impaired cognitive function, may provide further insight into the role of DMN dysfunction in cognitive deficits of schizophrenia. Independent component analysis (ICA) was applied to resting-state fMRI data to identify the DMN in each subject, and then general linear modeling based on the task-fMRI data was used to examine the different DMN activation patterns between groups. We observed that the SZ-Imp group, but not the SZ-Pre group, showed reduced suppression in the medial prefrontal cortex and posterior cingulated cortex when compared to the healthy controls (HC) group. Moreover, less DMN suppression was associated with poorer task performance in both HC and patient groups. Our findings provide the first direct evidence that disrupted DMN activity only exists in schizophrenia patients with impaired cognitive function, supporting the specific neuro-pathological role of inefficient DMN suppression in cognitive deficits of first-episode schizophrenia.

Using Affymetrix porcine Gene-Chip analyses, we found that Dickkopf2 (DKK2), a WNT antagonist, is differentially expressed in pre-ovulatory follicles between Large White and Chinese Taihu sows. This study aims to identify the regulatory factors responsible for DKK2 expression. Deletion fragment and mutation analyses identified DKK2-D3 as the porcine DKK2 core promoter. There were four C/EBPβ binding sites within the DKK2 core promoter. The C allele that results from a spontaneous alteration (DKK2 c.-1130 T > C) in the core promoter was associated with a higher total number born (TNB) and a higher number born alive (NBA) in all parities in a synthetic pig population. This was possibly the result of a change in C/EBPβ binding ability, which was confirmed using chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays (EMSA). Moreover, C/EBPβ specifically bound to and activated the DKK2 promoter, as revealed by mutation analysis, overexpression and RNA interference (RNAi) experiments. We also confirmed that miR-27a is a negative regulator of the DKK2 gene using miR-27a overexpression and inhibition experiments and mutation analyses. RTCA xCELLigence experiments showed that miR-27a suppressed Chinese hamster ovary (CHO) cell proliferation by down-regulating DKK2 gene expression. Taken together, our findings suggest that C/EBPβ and miR-27a control DKK2 transcription.

Chronic periodontitis is an oral disorder characterized with gingival inflammation and bone destruction. As the sixth-most prevalent condition affecting more than 743 million people around the world, it is classified as one of the seven destructive oral disorders. Early genetic epidemiological evidence indicated a major role for genetics in periodontal disease development. In this study, we conducted a two-stage comprehensive evaluation of the genetic susceptibility of FBXO38, AP3B2 and WHAMM with the diagnosis of severe chronic periodontitis. A total of 5,065 study subjects from the Han Chinese population consisting of 1,264 cases and 3,801 healthy controls were recruited, and 65 single nucleotide markers related to the three candidate genes were genotyped to investigate the susceptibility of patients with these polymorphisms to severe chronic periodontitis. To increase the coverage of genetic markers, we implemented imputation techniques to extend the number of tested makers to 416. Single marker and haplotype-based analyses were performed, and significant results were obtained for FBXO38 (rs10043775, P = 0.0009) and AP3B2 (rs11631963-rs11637433, CA, P = 9.98 × 10(-5); rs1864699-rs2099259-rs2278355, ATC, P = 3.84 × 10(-8)). Our findings provide direct evidence for the association of FBXO38 and AP3B2 with severe chronic periodontitis in the Han Chinese population.

The silk gland of Bombyx mori (BmSG) has gained significant attention by dint of superior synthesis and secretion of proteins. However, the application of BmSG bioreactor is still a controversial issue because of low yields of recombinant proteins. Here, a 3057 bp full-length coding sequence of Hpl was designed and transformed into the silkworm genome, and then the mutant (Hpl/Hpl) with specific expression of Hpl in posterior BmSG (BmPSG) was obtained. In the mutants, the transcription level of Fib-L and P25, and corresponding encoding proteins, did not decrease. However, the mRNA level of Fib-H was reduced by 71.1%, and Fib-H protein in the secreted fibroin was decreased from 91.86% to 71.01%. The mRNA level of Hpl was 0.73% and 0.74% of Fib-H and Fib-L, respectively, while HPL protein accounted for 18.85% of fibroin and 15.46% of the total amount of secreted silk protein. The exogenous protein was therefore very efficiently translated and secreted. Further analysis of differentially expressed gene (DEG) was carried out in the BmPSG cells and 891 DEGs were detected, of which 208 genes were related to protein metabolism. Reduced expression of endogenous silk proteins in the BmPSG could effectively improve the production efficiency of recombinant exogenous proteins.

Herein, we report the characterization of Limb expression 1-like, (LIX1L), a putative RNA-binding protein (RBP) containing a double-stranded RNA binding motif, which is highly expressed in various cancer tissues. Analysis of MALDI-TOF/TOF mass spectrometry and RNA immunoprecipitation-sequencing of interacting proteins and the microRNAs (miRNAs) bound to LIX1L revealed that LIX1L interacts with proteins (RIOK1, nucleolin and PABPC4) and miRNAs (has-miRNA-520a-5p, -300, -216b, -326, -190a, -548b-3p, -7-5p and -1296) in HEK-293 cells. Moreover, the reduction of phosphorylated Tyr(136) (pTyr(136)) in LIX1L through the homeodomain peptide, PY136, inhibited LIX1L-induced cell proliferation in vitro, and PY136 inhibited MKN45 cell proliferation in vivo. We also determined the miRNA-targeted genes and showed that was apoptosis induced through the reduction of pTyr(136). Moreover, ROS1, HCK, ABL1, ABL2, JAK3, LCK and TYR03 were identified as candidate kinases responsible for the phosphorylation of Tyr(136) of LIX1L. These data provide novel insights into the biological significance of LIX1L, suggesting that this protein might be an RBP, with implications for therapeutic approaches for targeting LIX1L in LIX1L-expressing cancer cells.

Experimentally-determined or computationally-predicted protein phosphorylation sites for distinctive species are becoming increasingly common. In this paper, we compare the predictive performance of a novel classification algorithm with different encoding schemes to develop a rice-specific protein phosphorylation site predictor. Our results imply that the combination of Amino acid occurrence Frequency with Composition of K-Spaced Amino Acid Pairs (AF-CKSAAP) provides the best description of relevant sequence features that surround a phosphorylation site. A support vector machine (SVM) using AF-CKSAAP achieves the best performance in classifying rice protein phophorylation sites when compared to the other algorithms. We have used SVM with AF-CKSAAP to construct a rice-specific protein phosphorylation sites predictor, Rice&#95;Phospho 1.0 (http://bioinformatics.fafu.edu.cn/rice&#95;phospho1.0). We measure the Accuracy (ACC) and Matthews Correlation Coefficient (MCC) of Rice&#95;Phospho 1.0 to be 82.0% and 0.64, significantly higher than those measures for other predictors such as Scansite, Musite, PlantPhos and PhosphoRice. Rice&#95;Phospho 1.0 also successfully predicted the experimentally identified phosphorylation sites in LOC&#95;Os03g51600.1, a protein sequence which did not appear in the training dataset. In summary, Rice&#95;phospho 1.0 outputs reliable predictions of protein phosphorylation sites in rice, and will serve as a useful tool to the community.

Prostate cancer is one of the most common noncutaneous malignancies in Western countries. Because there has been a debate regarding the relationship between the XRCC1-Arg399Gln and Arg280His polymorphisms and prostate cancer risk, we therefore performed this meta-analysis. The electronic databases PubMed, EMBASE, and Medline were searched prior to October 1, 2014. An odds ratio and 95% confidence interval were used to calculate association. Heterogeneity was tested by both a chi-square test and I statistic. Funnel plots and Egger's test were used to assess publication bias. All statistical analyses were performed using STATA 12.0 software. A significant association between the XRCC1-Arg399Gln polymorphism and prostate cancer risk was found under a homozygote model and a recessive model. A significant association between XRCC1-Arg280His and prostate cancer risk was found under a heterozygote model and a dominant model [corrected]. Overall, the results of this meta-analysis show that the XRCC1-Arg399Gln polymorphism may be associated with an increased risk for prostate cancer under the homozygote model and the recessive model. And XRCC1-Arg280His polymorphism is likely to be related with prostate cancer risk under the heterozygote model and the dominant model. Additional larger well-designed studies are needed to validate our results.

The effect of n-type interlayer in hybrid white organic light-emitting diodes (WOLEDs) has been systematically investigated by using various n-type materials. A new finding, that the triplet energy rather than electron mobility or hole-blocking ability of interlayer plays a more positive role in the performance of hybrid WOLEDs, is demonstrated. Based on the new finding, a more efficient n-type interlayer bis[2-(2-hydroxyphenyl)-pyridine] beryllium has been employed to realize a high-performance hybrid WOLED. The resulting device (without n-doping technology) exhibits low voltages (i.e., 2.8 V for 1 cd/m(2), 3.9 V for 100 cd/m(2)) and low efficiency roll-off (i.e., 11.5 cd/A at 100 cd/m(2) and 11.2 cd/A at 1000 cd/m(2)). At the display-relevant luminance of 100 cd/m(2), a total power efficiency of 16.0 lm/W, a color rendering index of 73 and an extremely long lifetime of 12596265 h are obtained. Such superior results not only comprehensively indicate that the n-type materials are effective interlayers to develop high-performance hybrid WOLEDs but also demonstrate a significant step towards real commercialization in WOLEDs.