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Abstract Congestive heart failure (CHF) is a complex clinical syndrome that significantly impacts patient outcomes, especially in critically ill patients admitted to intensive care units (ICUs). The aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT), has also been reported as a risk factor of cardiovascular diseases. However, few studies investigated the correlations between the AST/ALT ratio and ICU mortality in critically ill patients with CHF. This study investigates the association between the baseline AST/ALT ratio measured within the first 24 h of ICU admission and 28-day ICU all-cause mortality in critically ill patients with CHF. This retrospective cohort study included 4869 critically ill patients with CHF from the eICU Collaborative Research Database. Patients were categorized into tertiles based on their AST/ALT ratio: Tertile 1 (0.13–0.97), Tertile 2 (0.97–1.50), and Tertile 3 (1.50–5.89). Univariate and multivariate Cox proportional hazards regression models were used to evaluate the association between the AST/ALT ratio and 28-day ICU all-cause mortality. Nonlinear threshold effects and subgroup analyses were conducted to assess the robustness of the findings. Kaplan-Meier survival curves were generated to compare survival probabilities across tertiles. Participants with higher AST/ALT ratios were older, had higher illness severity, and experienced worse clinical outcomes. In univariate analysis, the AST/ALT ratio was significantly associated with 28-day ICU mortality (HR: 1.24, 95% CI 1.13–1.37, P

Abstract Acute cartilage injuries, such as intra-articular fractures and blunt impacts, frequently result in chondrocyte death and extracellular matrix (ECM) degradation, significantly elevating the risk of post-traumatic osteoarthritis (PTOA). Despite advances in treatment, no effective therapies currently exist to fully cure PTOA or halt its progression. This study explores the protective effects of the dietary fatty acid eicosapentaenoic acid (EPA) on human primary chondrocytes (HPCs) and cartilage explants exposed to mechanical overload and blunt trauma. HPCs were isolated and subjected to mechanical stretching using BioFlex six-well culture plates, while cartilage explants were subjected to impact loading via a customized drop tower. EPA was incorporated into the culture medium, followed by assays to evaluate cell viability, calcium (Ca²⁺) influx, apoptosis, reactive oxygen species (ROS) levels, and collagen type II alpha (Col-2a) expression. EPA treatment markedly decreased chondrocyte mechanical sensitivity, as demonstrated by enhanced cell viability and reduced lactate dehydrogenase (LDH) release. Furthermore, EPA inhibited Piezo1 activation, leading to lower intracellular Ca²⁺ concentrations, decreased apoptosis, and diminished ROS levels. In cartilage explants, EPA improved chondrocyte viability, minimized structural damage, and sustained higher Col-2a expression compared to the blunt trauma group. These results indicate that EPA effectively shields chondrocytes and cartilage explants from mechanical overload-induced damage by inhibiting Piezo1 activation and mitigating Ca²⁺ influx, apoptosis, and oxidative stress. The findings suggest that EPA supplementation could offer a promising strategy for preventing PTOA progression following acute cartilage injuries. Further research is warranted to assess the clinical applications of EPA and confirm its efficacy in larger animal models and human trials.

Technological innovation through various pathways is crucial for achieving carbon neutrality and peak carbon emissions. The Innovative City Pilot (ICP) initiative, a key effort to promote national innovation, has garnered increasing attention. However, most studies have not examined the effects of ICP on carbon emissions through diverse digital technologies. Using city-level data from 2000 to 2022, we constructed a staggered difference-in-differences (DID) model to analyze changes in carbon emissions before and after the ICP period in both ICP and non-ICP areas. The carbon emission reduction pathway of the ICP influences various forms of digital technology, which then empower local green product innovation, market-oriented innovation, and industrial innovation. The impact of ICP emission reduction through digital technology is more significant in western, first- and second-tier, sub-provincial, populous, and coastal cities. In conclusion, policymakers should tailor policies according to the action pathways of digital technology and specific city characteristics. We outline the specific pathways of green product innovation, market-oriented innovation, and industrial innovation enabled by digital technologies and provide policy recommendations for the sustainable development of China.

Objective: The aim of this study is to elucidate the underlying mechanism through which glial cell line-derived neurotrophic factor (GDNF) improves cognitive deficits in adults resulting from neonatal surgical interventions. Methods: Newborn Sprague–Dawley rats, regardless of gender, were randomly allocated into seven groups on postnatal day 7 as follows (n=15): (1) Control group (not subjected to anesthesia, surgery, or any pharmaceutical interventions); (2) GDNF group (received intracerebroventricular injection of GDNF); (3) Surgery group (underwent right carotid artery exposure under anesthesia with 3 % sevoflurane); (4) Surgery plus GDNF group; (5) Surgery plus GDNF and type II JAK inhibitor NVP-BBT594 (BBT594) group (administered intraperitoneal injection of BBT594); (6) BBT group; and (7) Surgery plus BBT group. Starting from postnatal day 33, all rats underwent Barnes maze and fear conditioning tests, followed by decapitation under sevoflurane anesthesia for subsequent analyses. The left hemibrains underwent Golgi staining, while the right hemibrains were used for hippocampal protein extraction to assess Protein kinase Mζ (PKMζ) and Kalirin expression through western blotting. Results: GDNF demonstrated a mitigating effect on spatial learning and memory impairment, as well as context-related fear memory impairment, reductions in dendritic total lengths, and spinal density within the hippocampus induced by surgical intervention. Notably, all of these ameliorative effects of GDNF were reversed upon administration of the RET inhibitor BBT594. Additionally, GDNF alleviated the downregulation of protein expression of PKMζ and Kalirin in the hippocampus of rats subjected to surgery, subsequently reversed by BBT594. Conclusion: The effective impact of GDNF on learning and memory impairment caused by surgical intervention appears to be mediated through the RET pathway. Moreover, GDNF may exert its influence by upregulating the expression of PKMζ and Kalirin, consequently enhancing the development of dendrites and dendritic spines.

Aims: Earlier studies have indicated an association between the TIMP1 polymorphism and the risk of certain autoimmune diseases, as well as a link between higher TIMP1 levels and blood-brain barrier (BBB) disruption in neuromyelitis optica spectrum disorders (NMOSD). This study aimed to explore the correlation between TIMP1 polymorphism and NMOSD phenotypes. Methods: Genotyping of three loci (rs4898, rs2070584, rs6609533) in the TIMP1 gene was performed in 126 NMOSD patients and 213 healthy controls (HCs) from North China using the SNaPshot sequencing technique, and a correlation analysis was done between phenotypes and TIMP1 genotype. Results: The frequency of the rs4898-T, rs2070584-T, and rs6609533-G alleles was significantly higher in NMOSD patients than those in HCs (p

Abstract A large number of motor vehicles and non-motorized vehicles mixed in the section of arterial highway crossing the town leads to many traffic problems. Therefore, it is necessary to set up a side divider between motorized and non-motorized lanes, and the appropriate spacing of lateral crossing openings to meet the needs of non-motorized vehicles crossing the highway has become a key issue that must be resolved. This paper investigates the traffic flow characteristics of mixed traffic flow on arterial highways through small town sections, and from the two dimensions of highway access efficiency and the psychological characteristics of cyclists, it calibrates the setting range of the spacing of non-motorized lateral crossing openings under different design speeds, which is used to regulate the behavior of non-motorized vehicles crossing the street, improve the safety level of the highway, reduce the lateral interference of the highway, and improve the road access efficiency. The accuracy of the research results is verified by microscopic simulation experiments, which proves that they can meet good expectations in practical engineering. The research results have theoretical significance and reference value for improving the status quo of machine-non-mixed traffic in the section of arterial highway passing through small towns, and enhancing the efficiency and safety of highway traffic. It also provides corresponding reference for the areas facing similar problems worldwide.

Abstract Objective Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune‐mediated disorder with aquaporin 4‐immunoglobulin G (AQP4‐IgG) in most settings. Soluble programmed death‐1 (sPD‐1) and soluble programmed death ligand 1 (sPD‐L1) play key roles in immunomodulation. We aim to assess the association of sPD‐1 and sPD‐L1 with cytokines and their clinical significance in AQP4‐IgG (+) NMOSD. Method We measured plasma sPD‐1, sPD‐L1, and 10 cytokines levels of 66 AQP4‐IgG (+) NMOSD patients, including 40 patients in attack (attack‐NMOSD) and 26 patients in remission (remission‐NMOSD) phases, and 28 healthy controls through ultrasensitive Simoa and SP‐X platform, respectively. We also performed >2 years (median) of follow‐up after testing and analyzed the relationship between the detection index and current and future clinical parameters. Result Plasma sPD‐1 level discriminated attack‐NMOSD from remission‐NMOSD (AUC = 0.692, p = 0.009). sPD‐1 and sPD‐L1 levels positively correlated with IL‐6 (rsPD‐1 = 0.313; rsPD‐L1 = 0.508), IFN‐γ (rsPD‐1 = 0.331; rsPD‐L1 = 0.456), and TNF‐α (rsPD‐1 = 0.451; rsPD‐L1 = 0.531) expression, as well as clinical indicators, including the EDSS score (rsPD‐1 = 0.331; rsPD‐L1 = 0.402), number of attacks (rsPD‐1 = 0.431) and segments of spinal cord involvement (rsPD‐1 = 0.462; rsPD‐L1 = 0.508). The risk of relapse within 2 years after sampling was associated with higher sPD‐1/sPD‐L1 ratio in attack‐NMOSD (p = 0.022; Exp(B) = 1.589). Interpretation Plasma sPD‐1 and sPD‐L1 levels reflected current disease severity and activity, and predicted future relapses in AQP4‐IgG (+) NMOSD, suggesting that they hold the potential to guide timely and targeted treatment.

Abstract The reconstruction of neural circuits from serial section electron microscopy (ssEM) images is being accelerated by automatic image segmentation methods. Segmentation accuracy is often limited by the preceding step of aligning 2D section images to create a 3D image stack. Precise and robust alignment in the presence of image artifacts is challenging, especially as datasets are attaining the petascale. We present a computational pipeline for aligning ssEM images with several key elements. Self-supervised convolutional nets are trained via metric learning to encode and align image pairs, and they are used to initialize iterative fine-tuning of alignment. A procedure called vector voting increases robustness to image artifacts or missing image data. For speedup the series is divided into blocks that are distributed to computational workers for alignment. The blocks are aligned to each other by composing transformations with decay, which achieves a global alignment without resorting to a time-consuming global optimization. We apply our pipeline to a whole fly brain dataset, and show improved accuracy relative to prior state of the art. We also demonstrate that our pipeline scales to a cubic millimeter of mouse visual cortex. Our pipeline is publicly available through two open source Python packages.

Geochemical measurements of stream sediments are practical for small-scale mineral exploration. However, traditional grid interpolation methods cause element concentrations to diffuse and smooth out anomalies, particularly in complex terrains, making it challenging to reflect the actual distribution of elements accurately. We applied the Dynamic Enhanced Weighted Drainage Catchment Basin (DE-WDCB) method to enhance the retention and identification of local anomalies by limiting the scope of analysis to specific drainage units. This method reduces interference from varying background values across different watersheds, effectively enhancing geochemical element anomalies and aligning better with geomorphic conditions. The DE-WDCB method was tested in the Duobaoshan–Heihe area, a significant copper polymetallic mineral district in northeastern China. Compared with traditional grid interpolation methods, the DE-WDCB method retained and strengthened low and weak abnormal information of favorable mineralization elements, particularly in the Luotuowaizi area. The method demonstrated a higher spatial coverage rate with mineral points and a more vital ore-indicating ability. Specifically, the DE-WDCB method identified anomalies with a mean accuracy of 63.57% (p < 0.05, 95% CI: 47.64%–79.50%), compared to 50.53% for traditional methods. In conclusion, in regions with a complex topography and watershed differences, the DE-WDCB method effectively reduces local geochemical background interference, accurately identifies low and weak geochemical anomalies, and better reflects the actual distribution of elements. This makes it a significantly advantageous method for geochemical anomaly extraction, delineating higher-confidence exploration targets in the Sandaowan–Luotuowaizi area in the east and the triangular area between Duobaoshan, Yubaoshan, Sankuanggou, and the midstream highlands of the Guanbird River in the west.

Abstract Background and Objective The neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) were significant and succinct indicators of systemic inflammation. We assessed the influence of stereotactic body radiotherapy (SBRT) on NLR and PLR in patients with locally advanced non‐small cell lung cancer (LA‐NSCLC). Methods We reviewed the medical data of patients with LA‐NSCLC who underwent SBRT between 1 January 2013 and 31 December 2018. NLR and PLR values recorded at pre‐ and post‐SBRT were examined. We assessed the correlation between pre/post‐SBRT NLR and PLR and survival outcomes. The decision tree evaluation was conducted using Chi‐square automatic detection. Results In total, 213 patients were included in the study with a median follow‐up duration of 40.00 (ranging from 5.28 to 100.70) months. Upon dichotomization by a median, we identified that post‐SBRT NLR > 5.5 and post‐SBRT PLR > 382.0 were negatively associated with shorter overall survival (OS). In the multivariate assessment, post‐SBRT PLR > 382.0 was the only factor. Based on post‐SBRT PLR, tumor locations, and tumor stage, we categorized patients into low, medium, or high‐risk groups. Conclusions Post‐SBRT PLR > 382.0 correlated with survival in patients undergoing SBRT. The decision tree model might play a role in future risk stratification to guide the clinical practice of individualized SBRT for LA‐NSCLC.

BackgroundPositive psychology is a vibrant field of study, and conceptualizations of the components of well-being have received a great deal of attention from researchers. The study of well-being literacy thus provides an innovative perspective for enhancing and sustaining individuals’ experiences of well-being.ObjectiveThis study aimed to examine the psychometric properties of the wellbeing literacy 6-item (Well-Lit 6) scale in Chinese military academy cadets.MethodsA total of 3,218 undergraduate students from five military academies in China were recruited to complete questionnaires online.Results(1) The items of the scale showed high discrimination; (2) The alpha coefficient of the scale was 0.986 and the split-half reliability was 0.981, indicating high homogeneous reliability and split-half reliability; (3) The scale model fitted well and displayed structural validity; (4) The correlation between well-being literacy and related indicators was significant, and the calibration correlation and convergent-discriminant validity of the scale were high; (5) After gradually adding demographic variables, known predictors factors and well-being literacy, the ∆R2 for subjective well-being, life satisfaction, depression, and anxiety ranged from 0.036 to 0.067, 0.184 to 0.340, and 0.009 to 0.017, respectively, showing high incremental validity; (6) the total well-being literacy scores differed significantly by gender, grade, and parenting style.ConclusionThe Chinese version of the Well-Lit 6 is reliable and valid in predicting and accessing the subjective well-being, life satisfaction, emotion regulation, and psychological resilience of Chinese military academy cadets.

Beer is one of the most widely consumed beverages in the world. Since the legalization of low-delta-9-tetrahydrocannabinol (THC) (Cannabis sativa in the United States, this controversial plant is being looked upon as a potential flavor additive for use in beer. Cannabis sativa shares similar aromatic and flavor characteristics to that of hops (Humulus lupulus). This study was designed to determine the influence ethanol concentration has on the cannabinoid and volatile compounds found in beer. Three experimental beers with varying ethanol (3, 6, and 9% ABV) concentrations were used for this experiment. Using dry-hopping practices and dosing from commercial brewing techniques, hemp was placed in the beer for five days at 25 °C. Cannabinoids and volatile compounds were analyzed following the completion of the dry-hemping process. Statistical differences were observed only for the cannabinoid, tetrahydrocannabinolic acid (THCA), while, no other individual cannabinoid or the summation of the total cannabinoids were statistically different. Volatile compounds were analyzed using gas chromatography–mass spectrometry (GC-MS). Statistical differences were observed between the monoterpenes and the sesquiterpenes volatile compound groups. In summary, ethanol concentration appears to have no impact on the extraction efficiency of cannabinoids but does appear to influence volatile compounds when hemp is added to beer through the dry-hemping process.

The exploration of space is becoming more feasible, and with this comes the possibility of performing fermentations in microgravity. Our study explores the potential effects of microgravity on a standard brewing model fermentation. As the fermentation of barley wort has been studied for centuries, there is an established foundation of knowledge with which to compare any changes that occur under microgravity. A modified ASBC miniature fermentation protocol (Yeast-14) was conducted within a Yuri 2.0 microgravity chamber to examine the response of Saccharomyces pastorianus to simulated microgravity conditions. Our findings reveal that yeast exhibited accelerated growth rates under microgravity compared to standard conditions. Additionally, the microgravity environment led to significantly lower levels of volatile compounds such as isoamyl acetate and 2-phenethyl acetate in the final product. Further genetic analysis showed significant downregulation of the ATF2 gene in the control group, potentially the mechanism behind the observed decrease in volatile compounds. These results show that while fermentation under microgravity is likely to eventually be commonplace, there may be changes in rate and gene expression that are beneficial or detrimental to the final product depending upon the desired characteristics.

Abstract Background In this study, we evaluated the efficacy and toxicity of stereotactic body radiotherapy (SBRT) as replacement strategy of conventionally fractionated radiation therapy in stage III non-small cell lung cancer (NSCLC) patients unfit for concurrent chemoradiation therapy (CRT). Methods We analyzed the clinical outcomes in patients with unresectable stage III NSCLC who received SBRT from January 1, 2013 to December 31, 2018. Both induction and consolidation chemotherapy were allowed. The survival rates and toxicities were calculated using the Kaplan-Meier method, and potential risk factors were investigated by multivariate Cox regression. Results A total of 213 consecutive patients who had received SBRT were enrolled. The median overall survival (OS) and progression-free survival (PFS) were 36.5 months and 16.1 months respectively. The estimated 1-, 2- and 3-year OS rates were 90.6%, 73.7% and 52.0%, respectively and the corresponding PFS rates were 69.5%, 25.4% and 15.0%, respectively. Treatment failures were largely (n = 151, 70.9%) distant metastases, with low rates of local (n = 74, 34.74%) and regional (n = 76, 35.68%) recurrences. In 13.1% patients (n = 28), ≥ grade (G) 3 toxicities were identified, including radiation pneumonia (n = 20, 9.4%) and bronchopulmonary hemorrhage (n = 8, 3.8%). None of the patients suffered from ≥ G 3 late toxic effects. Compared with patients with peripheral tumors, patients with central tumors had lower median OS (P

Abstract Background Osteoarthritis (OA) is a degenerative joint disease with lacking effective prevention targets. A disintegrin and metalloproteinase with thrombospondin motifs 12 (ADAMTS12) is a member of the ADAMTS family and is upregulated in OA pathologic tissues with no fully understood molecular mechanisms. Methods The anterior cruciate ligament transection (ACL-T) method was used to establish rat OA models, and interleukin-1 beta (IL-1β) was administered to induce rat chondrocyte inflammation. Cartilage damage was analyzed via hematoxylin-eosin, Periodic Acid-Schiff, safranin O-fast green, Osteoarthritis Research Society International score, and micro-computed tomography assays. Chondrocyte apoptosis was detected by flow cytometry and TdT dUTP nick-end labeling. Signal transducer and activator of transcription 1 (STAT1), ADAMTS12, and methyltransferase-like 3 (METTL3) levels were detected by immunohistochemistry, quantitative polymerase chain reaction (qPCR), western blot, or immunofluorescence assay. The binding ability was confirmed by chromatin immunoprecipitation-qPCR, electromobility shift assay, dual-luciferase reporter, or RNA immunoprecipitation (RIP) assay. The methylation level of STAT1 was analyzed by MeRIP-qPCR assay. STAT1 stability was investigated by actinomycin D assay. Results The STAT1 and ADAMTS12 expressions were significantly increased in the human and rat samples of cartilage injury, as well as in IL-1β-treated rat chondrocytes. STAT1 is bound to the promoter region of ADAMTS12 to activate its transcription. METTL3/ Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) mediated N6-methyladenosine modification of STAT1 promoted STAT1 mRNA stability, resulting in increased expression. ADAMTS12 expression was reduced and the IL-1β-induced inflammatory chondrocyte injury was attenuated by silencing METTL3. Additionally, knocking down METTL3 in ACL-T-produced OA rats reduced ADAMTS12 expression in their cartilage tissues, thereby alleviating cartilage damage. Conclusion METTL3/IGF2BP2 axis increases STAT1 stability and expression to promote OA progression by up-regulating ADAMTS12 expression.

Dipeptides have been shown to be an important taste substance in alcoholic beverages. However, the characterization of dipeptides in Chinese liquors was poor. Here, dansylation combined with liquid chromatography – mass spectrometry was employed to analyze dipeptides in eight liquors of two flavors. Consequently, 35 dipeptides were identified from liquors and 32 of them were quantified. Dipeptide quantification showed LODs smaller than 2.5 ng/mL. The calibration curves showed concentration spans from two to three orders of magnitude with satisfactory linearity. The matrix effects in low and high concentrations were from −25.71 % to 24.19 % and −14.82 % to 20.73 %, respectively. Intra- and inter-day precision is lower than 15 % for both low and high concentrations. The dipeptide contents in sauce flavor liquors were higher than those in strong flavor liquors. Ala- and -Phe dipeptides showed their unique trends between sauce and strong flavor liquors. This study provides new clues to evaluate taste of liquors.

Shell-and-tube heat exchanger (STHX) is widely used by virtue of its simple structure and high reliability, especially in a space-constrained surface ship. For the STHX of the surface ship, roll, pitch and other motion of the ship will affect the heat transfer performance, resistance characteristics and structural strength of the heat exchanger. Therefore, it is urgent to carry out numerical simulation research on three-dimensional thermal hydraulic characteristics of surface ship STHX under the marine conditions. In this paper, the numerical simulation of marine shell and tube heat exchanger of surface ship was carried out using the porous media model. Firstly, the mathematical physical model and numerical method are validated based on the experimental data of a marine engine cooling water shell and tube heat exchanger. The simulation results are in good agreement with the experimental results. The prediction errors of pressure drop and heat transfer are less than 10% and 1% respectively. The effect of marine conditions on the heat transfer characteristics of the heat exchanger is investigated by introducing the additional force model of marine condition to evaluate the effect of different motion parameters on the heat transfer performance of the heat exchanger. This study could provide a reference for the optimization of marine heat exchanger design.

Glucose oxidase (GOx) can specifically catalyze the conversion of β-d-glucose into gluconic acid and hydrogen peroxide (H2O2) in the presence of oxygen, making it promising for tumor starvation therapy and oxidative therapy. However, GOx's immunogenicity, poor in vivo stability, short half-life, and potential systemic toxicity, limit its application in cancer therapy. Nanocarriers are capable of improving the pharmacological properties of therapeutic drugs (e.g. stability, circulating half-life, and tumor accumulation) and lower toxicity, hence resolving GOx issues and enhancing its efficacy. Although the application of targeted nanocarriers based on GOx has recently flourished, this field has not yet been reviewed and evaluated. Herein, we initially examined the mechanism of GOx-based nanocarriers for enhanced tumor therapy. Also, we present a comprehensive and up-to-date review that highlights GOx-based nanocarriers for tumor targeting therapy. This review expands on GOx-based nano-targeted combination therapies from both passive and active targeting perspectives, meanwhile, active targeting is further classified into ligand-mediated targeting and physical-mediated targeting. Furthermore, this review also emphasizes the present challenges and promising advancements.

Osteoarthritis (OA) is associated with ferroptosis, a newly discovered form of programmed cell death associated with lipid peroxidation. Curcumin, the main monomer component in turmeric rhizomes, possesses antioxidant and anti-ferroptosis properties, but its effect on ferroptosis in chondrocytes of OA is unknown. This study aimed to investigate the protective effect and potential mechanism of curcumin on chondrocytes induced by erastin, a ferroptosis inducer. CCK-8 assays were used to assess cell viability in mouse primary chondrocytes treated with 3.33 μM erastin alone or in combination with different doses of curcumin. Various parameters were detected, including LDH, SOD, GSH-PX, MDA, ROS and Fe2+ contents. The ferroptosis-related proteins, such as SLC7A11, GPX4, TFR1, ACSL4, and FTH1, were examined using immunofluorescence and western blotting. Nrf2 was knocked down using siRNA to explore the molecular mechanism through which curcumin protects chondrocytes from erastin-induced ferroptosis. In a mouse model of knee ferroptosis induced by intracavity injection of 10 μL erastin (5 mg/mL), HE staining, Safranin O-Fast Green staining, and immunohistochemistry were employed to evaluate articular cartilage injury. The results demonstrated that erastin significantly suppressed the expression of SOD, GSH-PX, SLC7A11, GPX4, and FTH1 while upregulating the levels of LDH, MDA, ROS, ACSL4, and TFR1 in chondrocytes. Moreover, erastin-induced chondrocyte ferroptosis, lipid ROS, and Fe2+ production were reversed by curcumin. Additionally, curcumin significantly upregulated the expression level of the Nrf2 gene and protein. Silencing Nrf2 reversed the protective effect of curcumin on erastin-induced chondrocyte ferroptosis. In animal experiments, silencing Nrf2 counteracted the impact and damage of curcumin on erastin-induced ferroptosis of cartilage tissue in vivo, leading to significant inhibition of OA progression. Taken together, these findings suggest that curcumin can inhibit chondrocyte ferroptosis by activating the Nrf2 signaling pathway, providing further insight into the regulatory mechanism of curcumin in OA and supporting its potential therapeutic use in OA treatment.

Collaborative filtering (CF) algorithm is one of the most widely used recommendation algorithms in recommender systems. However, there is a data sparsity problem in the traditional CF algorithm, which may reduce the recommended efficiency of recommender systems. This paper proposes an improved collaborative filtering personalized recommendation (ICF) algorithm, which can effectively improve the data sparsity problem by reducing item space. By using the k-means clustering method to secondarily extract the similarity information, ICF algorithm can obtain the similarity information of users more accurately, thus improving the accuracy of recommender systems. The experiments using MovieLens and Netflix data set show that the ICF algorithm has a significant improvement in the accuracy and quality of recommendation.

Abstract Comparing the responses of closely related species to environmental changes is an efficient method to explore adaptive divergence, for a better understanding of the adaptive evolution of marine species under rapidly changing climates. Oysters are keystone species thrive in intertidal and estuarine areas where frequent environmental disturbance occurs including fluctuant salinity. The evolutionary divergence of two sister species of sympatric estuarine oysters, Crassostrea hongkongensis and Crassostrea ariakensis, in response to euryhaline habitats on phenotypes and gene expression, and the relative contribution of species effect, environment effect, and their interaction to the divergence were explored. After a 2‐month outplanting at high‐ and low‐salinity locations in the same estuary, the high growth rate, percent survival, and high tolerance indicated by physiological parameters suggested that the fitness of C. ariakensis was higher under high‐salinity conditions and that of C. hongkongensis was higher under low‐salinity conditions. Moreover, a transcriptomic analysis showed the two species exhibited differentiated transcriptional expression in high‐ and low‐salinity habitats, largely caused by the species effect. Several of the important pathways enriched in divergent genes between species were also salinity‐responsive pathways. Specifically, the pyruvate and taurine metabolism pathway and several solute carriers may contribute to the hyperosmotic adaptation of C. ariakensis, and some solute carriers may contribute to the hypoosmotic adaptation of C. hongkongensis. Our findings provide insights into the phenotypic and molecular mechanisms underlying salinity adaptation in marine mollusks, which will facilitate the assessment of the adaptive capacity of marine species in the context of climate change and will also provide practical information for marine resource conservation and aquaculture.

AIM: To identify the pathogenic gene in a family with primary open angle glaucoma(POAG)from Nantong, Jiang Province, and to analyze its clinical phenotype and pathogenic mechanism.METHOD: A POAG pedigree was reviewed and recruited from January 2020 to December 2020, which spans 5 generations, with 33 people in total. A total of 13 family members were enrolled in our study, of whom 4 members were diagnosed with POAG, 1 with ocular hypertension(OHT), and the other 8 members were unaffected. Detailed medical history was collected and a comprehensive ophthalmic examination was performed. High throughput sequencing was used to screen for possible pathogenic gene, and Sanger sequencing was used to verify candidate pathogenic gene.RESULT: All patients in this family were found to have elevated intraocular pressure(IOP)and diagnosed with glaucoma at a young age, requiring surgical treatments to control the IOP. The highest IOP of proband was up to 55mmHg. A heterozygous mutation(c.1197C>A, p.Phe399Leu)of LTBP2 gene was found in the proband genome by whole exon sequencing(WES). Sanger sequencing verified that the mutation was not isolated from the family disease.CONCLUSION: LTBP2 (c.1197C>A)mutation was not the pathogenic gene of POAG in this family. However, the pathogenic potential of LTBP2 gene in POAG cases is worth studying.

An integrated genomic and transcriptomic analysis of progeny from reciprocal crosses between tetraploid and hexaploid wheat species reveals parental contributions to gene expression during various stages of seed development.

Abstract Osteoarthritis (OA) is a chronic degenerative joint disease and is the most prevalent and disabling form of arthritis worldwide. Autophagy plays a vital role in OA. This study aimed to explore whether covalently closed circular RNA MSR (circRNA‐MSR) could affect the F‐box Only Protein 21 (FBXO21) expression by targeting microRNA‐761 (miR‐761), thereby affecting the autophagy in OA chondrocytes. Clinical OA tissues were collected, and circRNA‐MSR, miR‐761, and FBXO21 expressions were detected via quantitative real‐time polymerase chain reaction (qRT‐PCR). An in vitro OA model was constructed by treating C28/I2 cells with LPS and treating them with overexpression or knockdown vector of circRNA‐MSR, miR‐761, and FBXO21, and autophagy inhibitor 3‐MA. Fluorescence in situ hybridization (FISH) determined the location of circRNA‐MSR and miR‐761. Dual‐luciferase assay assessed circRNA‐MSR and miR‐761, along with the bindings of miR‐761 and FBXO21. Cell viability was detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. LC3 II/I, p62 and beclin 1 expressions were detected via the western blot. circRNA‐MSR and FBXO21 levels were elevated in OA, but miR‐761 level was inhibited. Suppressing circRNA‐MSR promoted the autophagy of LPS‐treated cells. circRNA‐MSR could bind to miR‐761 and inhibit its expression. MiR‐761 inhibition reversed the promoted autophagy caused by circRNA‐MSR knockdown in LPS‐treated C28/I2 cells. Moreover, miR‐761 could target FBXO21 and inhibit its expression. FBXO21 overexpression reversed the increased autophagy caused by miR‐761 overexpression in LPS‐treated C28/I2 cells. circRNA‐MSR could affect FBXO21 level via targeting miR‐761, thereby repressing autophagy in OA chondrocytes, providing a new target and strategy for OA treatment.

Abstract Knowledge Graph (KG) has been proven effective in representing and modeling structured information, especially in the medical domain. However, obtaining structured medical information usually depends on the manual processing of medical experts. Meanwhile, the construction of Medical Knowledge Graph (MKG) remains a crucial problem in medical informatization. This work presents a novel method for constructing MKGto drive the application of Rational Drug Use (RDU). We first collect and preprocess the corpora from various types of resources, and then develop a medical ontology via studying the concepts in RDUdomain, authoritative books and drug instructions. Based on the medical ontology, we formulate a scheme to annotate the corpora and construct the dataset for extracting entities and relations. We utilize two mechanisms to extract entities and relations respectively. The former is based on deep learning, while the latter is the rule-based method. In the last stage, we disambiguate and standardize the results of entity relation extraction to construct and enrich the MKG. The experimental results verify the effectiveness of the proposed methods.

Many research results have emerged in the past decade regarding multi-agent reinforcement learning. These include the successful application of asynchronous advantage actor-critic, double deep Q-network and other algorithms in multi-agent environments, and the more representative multi-agent training method based on the classical centralized training distributed execution algorithm QMIX. However, in a large-scale multi-agent environment, training becomes a major challenge due to the exponential growth of the state-action space. In this article, we design a training scheme from small-scale multi-agent training to large-scale multi-agent training. We use the transfer learning method to enable the training of large-scale agents to use the knowledge accumulated by training small-scale agents. We achieve policy transfer between tasks with different numbers of agents by designing a new dynamic state representation network, which uses a self-attention mechanism to capture and represent the local observations of agents. The dynamic state representation network makes it possible to expand the policy model from a few agents (4 agents, 10 agents) task to large-scale agents (16 agents, 50 agents) task. Furthermore, we conducted experiments in the famous real-time strategy game Starcraft II and the multi-agent research platform MAgent. And also set unmanned aerial vehicles trajectory planning simulations. Experimental results show that our approach not only reduces the time consumption of a large number of agent training tasks but also improves the final training performance.

As a pivotal integral component within electronic systems, analog circuits are of paramount importance for the timely detection and precise diagnosis of their faults. However, the objective reality of limited fault samples in operational devices with analog circuitry poses challenges to the direct applicability of existing diagnostic methods. This study proposes an innovative approach for fault diagnosis in analog circuits by integrating deep convolutional generative adversarial networks (DCGANs) with the Transformer architecture, addressing the problem of insufficient fault samples affecting diagnostic performance. Firstly, the employment of the continuous wavelet transform in combination with Morlet wavelet basis functions serves as a means to derive time–frequency images, enhancing fault feature recognition while converting time-domain signals into time–frequency representations. Furthermore, the augmentation of datasets utilizing deep convolutional GANs is employed to generate synthetic time–frequency signals from existing fault data. The Transformer-based fault diagnosis model was trained using a mixture of original signals and generated signals, and the model was subsequently tested. Through experiments involving single and multiple fault scenarios in three simulated circuits, a comparative analysis of the proposed approach was conducted with a number of established benchmark methods, and its effectiveness in various scenarios was evaluated. In addition, the ability of the proposed fault diagnosis technique was investigated in the presence of limited fault data samples. The outcome reveals that the proposed diagnostic method exhibits a consistently high overall accuracy of over 96% in diverse test scenarios. Moreover, it delivers satisfactory performance even when real sample sizes are as small as 150 instances in various fault categories.

Pathogenic enterotoxigenic Escherichia coli (ETEC) is a major cause of bacterial diarrhea in weaning piglets, which are vulnerable to changes in environment and feed. This study aimed to determine the effects of the ETEC challenge on piglet growth performance, diarrhea rate, jejunal microbial profile, jejunal morphology and goblet cell distribution. A total of 13 piglets from one litter were selected on postnatal day 21 and assigned to treatments with or without ETEC challenge at 1 × 108 CFUs, as ETEC group or control group, respectively. On postnatal day 28, samples were collected, followed by the detection of serum biochemical indexes and inflammatory indicators, HE staining, PAS staining and 16S rDNA gene amplicon sequencing. Results showed that the growth performance decreased, while the diarrhea rate increased for the ETEC group. The jejunum is the main segment of the injured intestine during the ETEC challenge. Compared with the control, the ETEC group displayed fewer goblet cells in the jejunum, where goblet cells are more distributed at the crypt and less distributed at the villus. In addition, ETEC piglets possessed higher abundances of the genus Desulfovibrio, genus Oxalobacter and genus Peptococus and lower abundances of the genus Prevotella 2, genus Flavonifractor and genus Blautra. In terms of alpha diversity, Chao 1 and observed features indexes were both increased for the ETEC group. Our study provides insights into jejunal histopathological impairment and microbial variation in response to ETEC infection for weaned piglets and is a valuable reference for researchers engaged in animal health research to select stress models.

ObjectivesTo analyze the global research trends of hypertrophic cardiomyopathy (HCM) from 2000 to 2022 and explore new frontiers in this field.MethodsWe reviewed the literature in the Web of Science Core Collection database from January 2000 to August 2022 using the retrieval strategy of medical subject headings combined with text words. We focused on articles and reviews that were published in English. Relevant data of the target publications, such as title, authors, organizations, abstract, keywords, published date, journal, and number of citations, were collected. The R software with the “bibliometrix” and VOSviewer software was used to process and visualize the information.ResultsAmong a total of 20,581 records related to HCM, 13,427 from 103 countries and regions, 8,676 affiliations, and 46,645 researchers were included. Most of the publications in this field were from the United States, followed by Japan, the United Kingdom, and China. We also report the top 10 institutions and most influential researchers, cited articles, and highest-frequency keywords (echocardiography, heart failure, sudden cardiac death, genetics, atrial fibrillation, magnetic resonance imaging/cardiac magnetic resonance, prognosis, mutation, arrhythmia, late gadolinium enhancement). In addition, keywords trend analysis indicated that the novel medicine Mavacamten, genetic diagnosis, and cardiac magnetic resonance have attracted the most attention for the treatment and diagnosis of HCM over the past five years.ConclusionThe present study reports on the global research trends of HCM over the past two decades using bibliometric analysis. It may enlighten new frontiers in the diagnosis, treatment, and risk prevention of HCM.

Intraoperative remifentanil infusion may paradoxically induce post-surgical hyperalgesia. Dexmedetomidine reportedly reduces opioid-induced hyperalgesia. Nalmefene selectively reverses several side-effects of opioids without impairing analgesia. Herein, this randomized, double-blind controlled trial investigated whether nalmefene, dexmedetomidine, and both drugs combined prevent remifentanil-induced hyperalgesia. One hundred and fifty patients undergoing elective laparoscopic gynecological surgery under desflurane anesthesia randomly received either intraoperative sufentanil 0.20 μg kg−1 (Group S), or remifentanil 0.20 μg kg−1 min−1 (Group R), or remifentanil and pre-anesthesia nalmefene 0.20 μg kg−1 (Group N), or remifentanil and pre-anesthesia dexmedetomidine 0.50 μg kg−1 (Group D), or remifentanil and the combination of dexmedetomidine 0.25 μg kg−1 and nalmefene 0.10 μg kg−1 (Group DN). The threshold of postoperative mechanical hyperalgesia (primary outcome) was measured with von Frey filaments. We also recorded pain intensity, analgesic consumptions, hyperalgesic area, and side-effects for 24 h postoperatively. Compared with Group S, remifentanil reduced hyperalgesic threshold on the forearm [mean 89.4 (SD 13.7) vs. 62.2 (10.7) g, p < 0.001] at postoperative 24 h. Pain threshold on the forearm at postoperative 24 h was significantly lower in Group R than in Groups N, D and DN [62.2 (10.7) vs. 71.1 (12.3), 72.4 (12.9) and 78.0 (13.8) g]. Compared with Group R, Postoperative pain intensity, analgesic consumption and hyperalgesic area were lower likewise in Groups D and DN. However, the incidence of intraoperative bradycardia was lower and post-anesthesia recovery time was shorter in Group DN than Group D. Preoperative therapy of dexmedetomidine and nalmefene combined attenuates postoperative hyperalgesia in patients undergoing laparoscopic gynecological surgery under desflurane-remifentanil anesthesia.

IntroductionIncorporation of transversus abdominis plane (TAP) block into multimodal analgesia has been emphasized in Enhanced Recovery protocols (ERPs). However, benefit is limited in clinical practice. A potential explanation is the short duration of analgesia of standard local anesthetics. Herein, this randomized, double-blind, controlled trial evaluated whether TAPB with long-acting compound lidocaine hydrochloride injection reduces postoperative pain.Methods164 patients undergoing elective gynecological laparotomy under sevoflurane anesthesia randomly received ultrasound-guided TAP block with either saline, or ropivacaine, or compound lidocaine before anesthesia induction. The postoperative pain intensity (primary outcome) was evaluated by pain 11-point numerical rating scale. We also recorded sufentanil consumptions, time to first flatus, side-effects and hospital stay after surgery.ResultsWe reported that pain scores at rest at postoperative 3h in group 0.375% ropivacaine was lower than that in group saline [mean 2.4 (SD 1.2) vs. 3.0 (1.0), p = 0.036]. Compared with saline, 0.4% and 0.6% compound lidocaine caused lower pain scores at rest at postoperative 12h [2.8 (0.9) vs. 2.1 (0.9) and 2.0 (0.9), p = 0.016 and p = 0.006]. Sufentanil usage for the first postoperative 48h was lower in group 0.6% compound lidocaine than group saline [24.2 (5.4) vs. 45.6 (7.5) µg, p

Tropical forests continue to suffer from various kinds of disturbances in the Anthropocene. An immediate impact of disturbances on forest ecosystems is the creation of numerous large and small canopy gaps, which dramatically affect forest structure and function. Yet, we know little about the effect of canopy gaps on forest successional trajectory. More specifically, the responses of seedlings from different successional stages to increased light intensity under large and small canopy gaps in understory remain unclear. In this study, dominant tree seedlings from early-, mid-, and late-successional stages were selected, respectively from a tropical montane forest in Hainan Island, China to study their growth rate, biomass and traits. Our results showed that the light condition under small canopy gaps (SG, 10–15% of full sunlight) and large canopy gaps (LG, 40–50% of full sunlight) induced greater increment of relative growth rates for seedlings from early- and mid-successional stages relative to that in late-successional stage. Both SG and LG also significantly increased photosynthesis rate, leaf area (LA), light saturation point (LSP), root mass ratio (RMR) and root: shoot ratio, but decreased specific leaf area (SLA) of seedlings across successional stages. Tree seedlings from the early-successional stage displayed the greatest decrease in leaf mass ratio, increase in LA, LSP, and RMR, in comparison to those from mid- and late- successional stages. Light condition and SLA were the most important factors for seedlings’ relative growth rate across successional stages. SLA connected the interaction between the light condition and successional stage on seedlings’ growth, thereby jointly explaining the 93% variation of seedlings’ growth, combining with area-based light saturated rate of CO2 assimilation. Our study highlights the distinct effect of disturbance-induced canopy gaps on seedling regeneration in the understory in tropical forest due to the variation of light intensity. We suspect that the seedlings from late-successional stage will recover relatively slow after disturbances causing canopy losses, which can have detrimental impacts on structure feature and successional trajectory in tropical forest, as well as forest-based ecosystem services.

The risk of hepatitis B virus (HBV) infection is higher in patients with diabetes mellitus, and diabetes mellitus is one of the metabolic complications of HBV infection. However, the cytokine profile of chronic hepatitis B (CHB) patients with type 2 diabetes mellitus (T2DM) is not fully understood. The aim of this study was to investigate the cytokine expression profile in CHB patients with T2DM, and to assess the regulatory function of cytokines to regulatory T cells (Tregs). Forty-four T2DM patients, 39 CHB patients, 17 patients with CHB and T2DM, and 21 control subjects were enrolled. Cytokine levels in the plasma were measured by Luminex multiplex assay. CD4+CD25+CD127dim/- Tregs were detected by flow cytometry. Tregs were purified and stimulated with recombinant human interleukin-15 (IL-15). The regulation of IL-15 on Tregs function was investigated by measuring cell number, IL-10/IL-35 secretion, and mRNA expression of immune checkpoint molecules in a Tregs+PBMC co-culture system. We found that levels of IL-1α, IL-6, and IL-33 were upregulated, while IFN-α, IL-2, IL-7, and IL-15 were downregulated in T2DM and CHB patients. CHB patients with T2DM had even lower plasma IL-7 and IL-15 levels. Tregs percentage was elevated in T2DM and CHB patients. CHB patients with T2DM had increased levels of Tregs, which correlated negatively with IL-15. Tregs showed stronger inhibitory activity in CHB patients with T2DM than in controls, T2DM, and CHB patients, which presented as reduction in cellular proliferation and induction of IL-10/IL-35 secretion. IL-15 suppressed Tregs function and inhibited the expression of immune checkpoint molecules in Tregs. The current data suggest that insufficient IL-15 levels and decreased responsiveness of Tregs to IL-15 signaling might contribute to strong immune dysfunction in CHB patients with T2DM.

This study aims to investigate the effect of exogenous melatonin (EMT) on cold injury (CI) and the physiological indicators of cucumbers under refrigerated conditions (2 °C). After being treated with different concentrations (0, 50, 100, and 500 μmol L−1) of EMT, the postharvest cucumbers were stored at 2 °C. During storage, cucumbers were collected at designed intervals (0, 3, 6, 9, and 12 d) and rewarmed for 2 days at room temperature (20–22 °C). The impacts of EMT were evaluated by periodically monitoring the changes in chilling injury index and physiological properties including weight loss rate, respiratory intensity, tissue electrolyte leakage, malondialdehyde (MDA) content, vitamin C, soluble protein content, free proline, and reactive oxygen species. Compared with the control, the treatment of EMT at the concentration of 100 μmol L−1 could significantly improve the contents of soluble protein, vitamin C, and free proline content and inhibit the rise of chilling injure index, weight loss rate, respiration intensity, tissue electrolyte leakage, MDA content, and reactive oxygen species. In addition, the results indicated that EMT treatment at a specific level (100 μmol L−1) had an effective impact on alleviating the CI of cucumbers during storage at low temperatures.

Abstract Background The present study aimed to identify a specific circular RNA (circRNA) for early diagnosis of gastric cancer (GC). Methods Totally 82 patients with GC, 30 with chronic nonatrophic gastritis and 30 with chronic atrophic gastritis were included in this study. Four of the 82 GC patients were selected for screening. Total RNA from malignant and adjacent tissue samples was extracted, and circRNAs in four patients were screened. According to the screening results, the eight most upregulated and downregulated circRNAs with a statistically significant association with GC were identified by real-time fluorescent quantitative polymerase chain reaction (PCR). Then, the most regulated circRNA was selected for further sensitivity and specificity assessments. CircRNA expression was examined by quantitative reverse transcriptase PCR in 78 GC (21 and 57 early and advanced GC, respectively) and adjacent tissue samples, as well as in gastric fluid samples from 30 patients with chronic nonatrophic gastritis, 30 with chronic atrophic gastritis, and 78 GC. Results A total of 445 circRNAs, including 69 upregulated and 376 downregulated circRNAs, showed significantly altered expression in GC tissue samples. Hsa_circ_000780 was significantly downregulated in 80.77% of GC tissue samples, with levels in GC tissue samples correlating with tumor size, tumor stage, T stage, venous invasion, carcinoembryonic antigen amounts, and carbohydrate antigen 19–9 levels. Strikingly, this circRNA was found in the gastric fluid of patients with early and advanced GC. Conclusions The present study uncovered a new circRNA expression profile in human GC, with hsa_circ_000780 significantly downregulated in GC tissue and gastric fluid specimens. These findings indicate that hsa_circ_000780 should be considered a novel biomarker for early GC screening.

Technology spillover is crucial to achieving economic development while also reducing CO2 emissions. The success of diffusion depends critically upon advanced intellectual property rights (IPR) protection and the level of infrastructure. Several studies have discussed the relationship between technology spillover and CO2 emissions. However, very few studies have addressed the impacts of socio-economic factors, particularly IPR protection and transportation infrastructure (TI) (the two concepts that are directly related to technology spillover), on this relationship. Therefore, this study used an extended Environmental Kuznets Curve (EKC) model to explore the relationship between technology spillover and CO2 emissions in China from 1997 to 2018. The study accounted for two threshold variables (IPR protection and TI) in a threshold model to explore the nonlinear effect of technology spillover on CO2 emissions. The findings revealed that: (1) when the IPR protection value was below 8.169, different forms of technology spillover had an optimal effect on CO2 emission reduction; (2) the scale of TI construction should be moderate and below the threshold value; otherwise, greater environmental pressure would occur; and (3) threshold points varied geographically. The results indicated that the level of IPR protection and TI should be adapted to the regional development characteristics to promote economic development and minimize environmental impacts.

The improvement of transportation green total factor productivity (GTFP) is crucial to the high-quality development of China’s economy under the new normal. Through dynamic and cross-regional comparison of transportation TFP and transportation GTFP, the driving force of transportation GTFP growth was analyzed. An augmented production function model and the geographically weighted regression (GWR) model were combined to analyze the spatial impact of technological progress on transportation GTFP The results are as follows: the effect of R&D investment on transportation GTFP first decreases and then increases. The impact factor of interprovincial technology spillover (DS) on transportation GTFP was always negative during the study period. The influence of foreign direct investment on transportation GTFP depends on the “pollution haven” and “pollution halo” effects. We highlighted the need for regional coordinated development and encouragement of green technology spillover. We should also promote the GTFP growth with regional differentiation.

Abstract Both biochar and nitrogen (N) addition have been proposed for enhancing plant productivity and increasing carbon (C) sequestration. Although numerous studies have been conducted to examine responses of soil greenhouse gas (GHG) fluxes to biochar or N addition, biochar is often co‐applied with N fertilizer and the interactive effects of the two factors still remain unclear. In this study, we performed a meta‐analysis of manipulative experiments with 267 two‐factor observations to quantify the main and interactive effects of biochar and N addition on soil GHG fluxes at a global scale. Our results showed that biochar addition significantly increased soil CO2 emission by 10.1%, but decreased N2O emission by 14.7%. Meanwhile, N addition increased both soil CO2 and N2O emissions by 11.6% and 288%, respectively. The combination of biochar and N addition also exhibited significant positive effect on CO2 (+18.0%) and N2O (+148%) emissions, but there were non‐significant changes in CH4 fluxes. Consequently, antagonistic interaction between biochar and N addition was observed in soil GHG fluxes and their global warming potential (GWP), except for CH4 uptake showing an additive interaction. This synthesis highlights the importance of the interactive effects between biochar and N addition, providing a quantitative basis to develop sustainable strategies toward widespread application of biochar to preserve cropping system and mitigate climate change.

Background: Traditional Chinese medicine (TCM), a main form of complementary and alternative medicine provides a potential possibility for demyelinating disease of the central nervous system (DDC) management and has been applied in considerable amounts of patients with this disorder. Nevertheless, powerful real-world evidences regarding the epidemiological and clinical characteristics, safety, and outcomes of TCM in DDC are lacking. The primary objective of the Demyelinating Diseases of the Central Nervous System Registry for Patients with Traditional Chinese Medicine (DATE-TCM) is to create an organized multicenter data collection structure to define integrative characteristics of DDC patients treated with TCM in an endeavor to fill these knowledge gaps to better inform clinical care and health policy.Method: This study provides a prospective and voluntary registry by using a web-based system. Baseline data will be recorded and subsequently regular follow-up visits will be implemented every 3–6 months for a total of 5 years. The primary outcome is Annualized Aggregate Relapse Rate at 5-year follow-up.Results: DATE-TCM is currently designed to capture the multidimensional (epidemiologic, demographic, clinical, etc.) features of DDC patients receiving TCM treatment, the type and long-term safety and efficacy of TCM intervenes in the DDC populations, as well as the interaction of TCM treatments and disease modifying therapies in the management of DDC, aiming to include 2000 eligible adult DDC patients with TCM intervenes from 35 participating centers, covering 77.4% of provincial administrative regions of mainland China.Conclusion: DATE-TCM is the first, largest, most geographically extensive, and standard registry-based observational study that systematically document the real-world data regarding the TCM application in the DDC populations, which will be extraordinarily important for clarifying the comprehensive characteristics and outcomes of TCM in DDC, further shed light on standardizing and optimizing the TCM measures for DDC management and establishing evidence-based clinical practice guidelines for TCM application in DDC.

BackgroundThis study aimed to investigate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and D-dimer-to-fibrinogen ratio (DFR) as predictors of pneumonia and poor outcomes in patients with acute intracerebral hemorrhage (ICH).MethodsWe retrospectively examined patients with acute ICH treated in our institution from May 2018 to July 2020. Patient characteristics, laboratory testing data, radiologic imaging data, and 90-day outcomes were recorded and analyzed.ResultsAmong the 329 patients included for analysis, 183 (55.6%) developed pneumonia. Systolic blood pressure, initial hematoma volume, D-dimer concentration, NLR, PLR, DFR, and white blood cell, platelet, neutrophil, and lymphocyte counts at admission were significantly higher in patients who developed pneumonia than in those who did not; however, the Glasgow coma scale (GCS) score at admission was significantly lower in pneumonia patients compared with non-pneumonia patients (all P

Here, the authors present a comparative analyses on vaginal and uterine microbiota in 1223 samples derived from 655 women with chronic endometritis, which, combined with animal experiments, characterize the microbial translocation in the female reproductive tract and its role in modulating uterine health.

The Hong Kong oyster (Crassostrea hongkongensis) lives in the brackish waters of estuaries in the intertidal zone and has a high resistance to low levels of salinity, but low resistance to higher levels. Juveniles are more sensitive to high levels of salinity than adults. To better understand the mechanisms underlying these differences, we performed a high-salinity stress analysis of juvenile and adult Hong Kong oysters. Trait analysis between groups showed that Na+-K+-ATPase activity, T-AOC, betaine, taurine and glycogen content of the high-salinity group were almost all higher than that of the control group at 8 h under high-salt stress, but lower than that of the control group at 96 h. The differences are more significant in Adult population. The results indicate that these indexes are related to the salinity adaptability of oysters. Enrichment analysis and protein-protein interaction (PPI) network analysis of the differentially expressed genes (DEGs) screened from transcriptomic data showed that their functions were mainly related to the oxidation-reduction process, immune response, protein ubiquitination and ATP synthesis. Furthermore, a weighted gene co-expression network analysis (WGCNA) of all samples showed that the hub gene functions were mainly associated with the oxidation-reduction process and immune response. These results indicate that immune response-related and antioxidant genes play key roles in the adaptability of Hong Kong oysters to high salinity. This study provides new insights and enriches our current understanding of the salinity adaptation mechanisms in oysters.

With the widespread application of GNSS, the delicate handling of biases among different systems and different frequencies is of critical importance, wherein the inter-frequency clock biases (IFCBs) and observable-specific signal biases (OSBs) should be carefully corrected. Usually, a serial approach is used to calculate these products. To accelerate the computation speed and reduce the time delay, a multicore parallel estimation strategy for IFCBs, code, and phase OSBs by utilizing task parallel library (TPL) is proposed, the parallel computations, including precise point positioning (PPP), IFCBs, and OSBs estimation, being carried out on the basis of data parallelisms and task-based asynchronous programming. Three weeks of observables from the multi-GNSS experiment campaign (MGEX) network is utilized. The result shows that the IFCB errors of GPS Block IIF and GLONASS M+ satellites are nonnegligible, in which the GLONASS M+ satellite R21 shows the largest IFCB of more than 0.60 m, while those of other systems and frequencies are marginal, and the code OSBs present excellent stability with a standard deviation (STD) of 0.10 ns for GPS and approximately 0.20 ns for other satellite systems. Besides, the phase OSBs of all systems show the stability of better than 0.10 ns, wherein the Galileo satellites show the best performance of 0.01 ns. Compared with the single-core serial computing method, the acceleration rates for IFCBs and OSBs estimation are 3.10, 5.53, 9.66, and 17.04 times higher using four, eight, sixteen, and thirty-two physical cores, respectively, through multi-core parallelized execution.

Direct infusion nanoelectrospray high-resolution mass spectrometry (DI-nESI-HRMS) is a promising tool for high-throughput metabolomics analysis. However, metabolite assignment is limited by the inadequate mass accuracy and chemical space of the metabolome database. Here, a serum metabolome characterization method was proposed to make full use of the potential of DI-nESI-HRMS. Different from the widely used database search approach, unambiguous formula assignments were achieved by a reaction network combined with mass accuracy and isotopic patterns filter. To provide enough initial known nodes, an initial network was directly constructed by known metabolite formulas. Then experimental formula candidates were screened by the predefined reaction with the network. The effects of sources and scales of networks on assignment performance were investigated. Further, a scoring rule for filtering unambiguous formula candidates was proposed. The developed approach was validated by a pooled serum sample spiked with reference standards. The coverage and accuracy rates for the spiked standards were 98.9% and 93.6%, respectively. A total of 1958 monoisotopic features were assigned with unique formula candidates for the pooled serum, which is twice more than the database search. Finally, a case study of serum metabolomics in diabetes was carried out using the developed method.

PurposeThe correlation of abnormal glucose metabolism and thyroid carcinoma, especially the aggressiveness of thyroid cancer, still remains controversial. We conducted this study to investigate the relationship between abnormal glucose metabolism parameters and differentiated thyroid carcinoma (DTC) in the Chinese population.Materials and MethodsThe study was designed as a hospital-based case–control study and was approved by the Ethics Committee of our hospital and registered in the Clinical Trial Protocol Registration and Results System (Registration code: NCT 03006289). From January 1, 2018 to June 30, 2021, a total of 377 DTC patients were enrolled in the study. Demographic and general characteristics, details of thyroid surgery and histopathological results, hematological test indicators were collected. Glucose metabolism parameters were calculated. Variables were analyzed by t-test, ANOVA, chi-squared analysis and Fisher’s exact test. Pearson bi-variate correlation and Spearman’s correlation analysis were used for bi-variate analysis.ResultsMore than 40% of patients with DTC were multifocality, more than half were extra-glandular invasion, and nearly 85% complied by lymph node metastasis. The prevalence of diabetes mellitus (DM) was about 10.08% in DTC patients. It was found that the proportion of postprandial 2 h blood glucose ≥11.1mmol/L and HbA1c ≥6.5% was significantly higher than the known proportion of DM (17.8%, 16.7% vs. 10.08%). Additionally, 87.3% of the DTC patients in this study had varying degrees of insulin resistance. Further analysis found that higher T staging was associated with higher levels of area under curve of C-peptide (P = 0.029), insulin sensitivity index (P = 0.012) and C-peptide sensitivity index (P = 0.016). A delayed peak of insulin secretion was found to be positive related with capsule invasion (r = 0.206, P = 0.004). In patients without a DM history, homeostasis model assessment of insulin resistance (P = 0.017), insulin sensitivity index (P = 0.019) and C-peptide sensitivity index (P = 0.020) were statistic associated with T staging. Also, the glucose metabolism parameter at 3-hour after a meal was related to a larger number of metastatic lymph nodes.ConclusionAbnormal glucose metabolism, namely, DM, hyperinsulinemia and insulin resistance, were significantly associated with the carcinogensis and aggressiveness of DTC.

Objective: To validate the eighth edition of the AJCC staging system in patients with pancreatic adenocarcinoma receiving only stereotactic body radiation therapy and chemotherapy, and to propose modifications to improve prognostic accuracy. Methods: Patients with pathologically confirmed pancreatic adenocarcinoma without metastasis who were undergoing only chemoradiotherapy were included and staged according to the seventh and eighth editions of the AJCC staging system. Meanwhile, another group of stage T4 patients from the above enrollment with only portal vein involvement with or without tumor thrombi (PV ± PVTT) were retrieved for survival comparisons. Modifications were proposed according to the survival comparisons. A cohort from the SEER database was used for external validation of the modified staging system. Results: A total of 683 patients were included. Patients with N2 or N1 but different T stages had significantly different survival outcomes according to the eighth edition. The survival of patients with PV ± PVTT was comparable to that of patients with T4 tumors. The concordance index of the seventh and eighth editions, and the modified staging system was 0.744 (95%CI: 0.718–0.769), 0.750 (95%CI: 0.725–0.775), and 0.788 (95%CI: 0.762–0.813), respectively. For external validation, the concordance index was 0.744 (95%CI: 0.718–0.770), 0.750 (95%CI: 0.724–0.776), and 0.788 (95%CI: 0.762–0.814), respectively. Conclusions: The modified staging system is suggested to have the most accurate prognostic value. Hence, PV ± PVTT should be added to the definition of T4 tumors regardless of tumor size. Patients with N2 or N1 in different T stages could be regrouped into different substages. Additionally, stage III should be subclassified into IIIA (T3N2 and T4N0) and IIIB (T4N1-2).

Cuprotosis is a novel cell death mechanism that can be explored to treat various tumors. A few studies on the role of cuprotosis-related long noncoding RNA (lncRNA) in the development and prognosis of kidney renal clear cell carcinoma (KIRC) have been reported. We aimed to study the relationship between the prognosis of patients suffering from KIRC and lncRNAs associated with cuprotosis. The Cancer Genome Atlas (TCGA) database was analyzed, and the transcriptome data and clinical information on the patients with KIRC were obtained. The cuprotosis-related lncRNAs were identified by using Pearson correlation analysis, and the significant changes in the lncRNAs associated with KIRC were studied by conducting the T-test. The cuprotosis-related lncRNAs with KIRC prognostic values were identified by using the univariate Cox analysis, least absolute shrinkage and selection operator (LASSO), and support vector machine (SVM) methods. A prognostic marker composed of three cuprotosis-related lncRNAs was identified following the multivariate regression analysis method. Patients with KIRC were divided into two groups based on the expression characteristics of three cuprotosis-related lncRNAs by using the K nearest neighbor (KNN) cluster analysis method. Significant differences in survival were observed between the two groups. In addition, the results obtained following the independent prognostic analysis of the risk score (RS) and clinical correlation revealed that the three cuprotosis-related lncRNA prognostic markers could accurately predict the prognosis of patients with KIRC. The results reported herein provide new insights into the pathogenesis of KIRC and the contribution of lncRNAs associated with cuprotosis. The results also helped identify a prognostic indicator that could potentially provide information for KIRC treatment.

Flammulina velutipes is one of the most important edible mushrooms, which quickly decays with a short shelf life. However, little is known about the effect of ɛ-polylysine (ɛ-PL) or nisin on the survival of Lactococcus lactis (L. lactis) during the storage at constant temperatures. The objective of this study was to investigate the effect of ɛ-PL or nisin on the growth of L. lactis and background (BK) microorganisms in fresh Flammulina velutipes fruiting bodies (FVFB) and develop mathematical models to predict their growth behavior. The effect of ɛ-PL (0.15 and 0.30 g/kg) or nisin (0.10 and 0.20 g/kg) on the growth of L. lactis and BK microorganisms in FVFB was analyzed at 4, 16, and 20°C. The lag phase of L. lactis was extended, and the specific growth rate was decreased by increasing concentrations of ɛ-PL or nisin and lowering the temperature. The results showed that ɛ-PL or nisin could control the growth of L. lactis in FVFB. However, the growth of BK microorganisms was not affected by ɛ-PL or nisin. The growth of L. lactis and BK microorganisms could be successfully described by the reparameterized Gompertz and no lag phase models, respectively. Additionally, ɛ-PL or nisin could maintain the quality of FVFB by preventing weight loss, color-changing, and decreasing soluble solid content in FVFB at 4°C. These results suggest that ɛ-PL or nisin in combination with low temperature may inhibit the growth of L. lactis in FVFB and prevent the decrease in the quality of FVFB.

Marine dynamic disasters, such as storm surges and huge waves, can cause large economic and human losses. The assessment of marine dynamic disasters is, thus, important, but improvements to its reliability are needed. The current study improved and integrated the assessment from the perspective of multi-factor coupling. Using a weighted index system, a marine dynamic disaster assessment indicator system suitable for China’s coastal waters was established, and a method for calculating the weight of disaster indicators was proposed from the perspective of rapid assessment. To reduce the assessment deviation in coastal waters, a multi-factor coupling algorithm was proposed. This algorithm obtained amplitude variations of wave orbital motion in horizontal and vertical directions, which was used to evaluate the influence of background current and terrain slope on coastal ocean waves. Landsat 8 remote sensing images were used to carry out an object-oriented extraction of raft and cage aquaculture areas in China’s coastal waters. The aquaculture density was then used as the main basis for a vulnerability assessment. Finally, the whole assessment system was integrated and verified during a typical storm surge process in coastal waters around the Shandong Peninsula in China. The coupled variations were also added to the assessment process and increased the risk value by an average of 12% in the High Sea States of the case study.