Search

Abstract Sepsis-induced cardiomyopathy (SIC) is described as a reversible myocardial depression that occurs in patients with septic shock. Increasing evidence shows that microRNA-194-5p (miR-194-5p) participates in the regulation of oxidative stress, mitochondrial dysfunction, and apoptosis and its expression is associated with the occurrence and progression of cardiovascular disease; however, the effects of miR-194-5p in SIC are still unclear. This study explores whether miR-194-5p could modulate SIC by affecting oxidative stress, mitochondrial function, and apoptosis. Experimental septic mice were induced by intraperitoneal injection of lipopolysaccharide (LPS) in C57BL/6J mice. The biological role of miR-194-5p in SIC in vivo was investigated using cardiac echocardiography, ELISA, western blot, qRT-PCR, transmission electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, bioinformatics analysis, and dual-luciferase reporter gene assay. Our major finding is that miR-194-5p antagomir mitigates sepsis-induced cardiac dysfunction, inflammation, oxidative stress, apoptosis and mitochondrial dysfunction in the hearts of septic mice, while miR-194-5p agomir triggers the opposite effects. Furthermore, dual-specificity phosphatase 9 (DUSP9) is a direct target of miR-194-5p and the cardioprotective effects of miR-194-5p antagomir on cardiac dysfunction, inflammation, apoptosis, mitochondrial dysfunction and oxidative stress are abolished through inhibiting DUSP9. Therefore, miR-194-5p inhibition could mitigate SIC via DUSP9 in vivo and the novel miR-194-5p/DUSP9 axis might be the potential treatment targets for SIC patients.

Abstract The dose–response of intravenous lidocaine in preventing postoperative vomiting (POV) in children remains unclear. This study investigated whether intravenous lidocaine dose-dependently decreased POV risk within 24 h postoperatively in children undergoing tonsillectomy (with or without adenoidectomy) without severe complications. Patients aged 3–12 years (American Society of Anesthesiologists grade I–II) scheduled for elective tonsillectomy (with or without adenoidectomy) were enroled from December 2021 to March 2022. They were randomly grouped according to the lidocaine dose (A [0 mg kg−1], B [1 mg kg−1], C [1.5 mg kg−1], and D [2 mg kg−1]) and were administered the same induction protocol (sufentanil, propofol, and suxamethonium chloride). Anaesthesia was maintained with sevoflurane. The incidence of POV within 24 h postoperatively was 46, 40, 36, and 20% in groups A, B, C, and D, respectively, with significant differences between groups D and A. Postoperative analgesic rescues in groups A, B, C, and D were 62, 36, 34, and 16%, respectively, with significant differences between groups D and B, C and A, and D and A. No severe adverse events were reported. Intravenous lidocaine has a dose-dependent effect on reducing the risk of POV in children undergoing tonsillectomy (with or without adenoidectomy) without serious adverse events. Trial registration: Chinese Clinical Trial Registry, ChiCTR2100053006.

Abstract The precise forecasting of air quality is of great significance as an integral component of early warning systems. This remains a formidable challenge owing to the limited information of emission source and the considerable uncertainties inherent in dynamic processes. To improve the accuracy of air quality forecasting, this work proposes a new spatiotemporal hybrid deep learning model based on variational mode decomposition (VMD), graph attention networks (GAT) and bi-directional long short-term memory (BiLSTM), referred to as VMD–GAT–BiLSTM, for air quality forecasting. The proposed model initially employ a VMD to decompose original PM2.5 data into a series of relatively stable sub-sequences, thus reducing the influence of unknown factors on model prediction capabilities. For each sub-sequence, a GAT is then designed to explore deep spatial relationships among different monitoring stations. Next, a BiLSTM is utilized to learn the temporal features of each decomposed sub-sequence. Finally, the forecasting results of each decomposed sub-sequence are aggregated and summed as the final air quality prediction results. Experiment results on the collected Beijing air quality dataset show that the proposed model presents superior performance to other used methods on both short-term and long-term air quality forecasting tasks.

Abstract The study aims to investigate the predictive capability of machine learning algorithms for omental metastasis in locally advanced gastric cancer (LAGC) and to compare the performance metrics of various machine learning predictive models. A retrospective collection of 478 pathologically confirmed LAGC patients was undertaken, encompassing both clinical features and arterial phase computed tomography images. Radiomic features were extracted using 3D Slicer software. Clinical and radiomic features were further filtered through lasso regression. Selected clinical and radiomic features were used to construct omental metastasis predictive models using support vector machine (SVM), decision tree (DT), random forest (RF), K-nearest neighbors (KNN), and logistic regression (LR). The models’ performance metrics included accuracy, area under the curve (AUC) of the receiver operating characteristic curve, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In the training cohort, the RF predictive model surpassed LR, SVM, DT, and KNN in terms of accuracy, AUC, sensitivity, specificity, PPV, and NPV. Compared to the other four predictive models, the RF model significantly improved PPV. In the test cohort, all five machine learning predictive models exhibited lower PPVs. The DT model demonstrated the most significant variation in performance metrics relative to the other models, with a sensitivity of 0.231 and specificity of 0.990. The LR-based predictive model had the lowest PPV at 0.210, compared to the other four models. In the external validation cohort, the performance metrics of the predictive models were generally consistent with those in the test cohort. The LR-based model for predicting omental metastasis exhibited a lower PPV. Among the machine learning algorithms, the RF predictive model demonstrated higher accuracy and improved PPV relative to LR, SVM, KNN, and DT models.

Abstract As countries attach importance to environmental protection, clean energy has become a hot topic. Among them, solar energy, as one of the efficient and easily accessible clean energy sources, has received widespread attention. An essential component in converting solar energy into electricity are solar cells. However, a major optimization difficulty remains in precisely and effectively calculating the parameters of photovoltaic (PV) models. In this regard, this study introduces an improved rime optimization algorithm (RIME), namely ERINMRIME, which integrates the Nelder-Mead simplex (NMs) with the environment random interaction (ERI) strategy. In the later phases of ERINMRIME, the ERI strategy serves as a complementary mechanism for augmenting the solution space exploration ability of the agent. By facilitating external interactions, this method improves the algorithm’s efficacy in conducting a global search by keeping it from becoming stuck in local optima. Moreover, by incorporating NMs, ERINMRIME enhances its ability to do local searches, leading to improved space exploration. To evaluate ERINMRIME's optimization performance on PV models, this study conducted experiments on four different models: the single diode model (SDM), the double diode model (DDM), the three-diode model (TDM), and the photovoltaic (PV) module model. The experimental results show that ERINMRIME reduces root mean square error for SDM, DDM, TDM, and PV module models by 46.23%, 59.32%, 61.49%, and 23.95%, respectively, compared with the original RIME. Furthermore, this study compared ERINMRIME with nine improved classical algorithms. The results show that ERINMRIME is a remarkable competitor. Ultimately, this study evaluated the performance of ERINMRIME across three distinct commercial PV models, while considering varying irradiation and temperature conditions. The performance of ERINMRIME is superior to existing similar algorithms in different irradiation and temperature conditions. Therefore, ERINMRIME is an algorithm with great potential in identifying and recognizing unknown parameters of PV models.

Abstract Image segmentation techniques play a vital role in aiding COVID-19 diagnosis. Multi-threshold image segmentation methods are favored for their computational simplicity and operational efficiency. Existing threshold selection techniques in multi-threshold image segmentation, such as Kapur based on exhaustive enumeration, often hamper efficiency and accuracy. The whale optimization algorithm (WOA) has shown promise in addressing this challenge, but issues persist, including poor stability, low efficiency, and accuracy in COVID-19 threshold image segmentation. To tackle these issues, we introduce a Latin hypercube sampling initialization-based multi-strategy enhanced WOA (CAGWOA). It incorporates a COS sampling initialization strategy (COSI), an adaptive global search approach (GS), and an all-dimensional neighborhood mechanism (ADN). COSI leverages probability density functions created from Latin hypercube sampling, ensuring even solution space coverage to improve the stability of the segmentation model. GS widens the exploration scope to combat stagnation during iterations and improve segmentation efficiency. ADN refines convergence accuracy around optimal individuals to improve segmentation accuracy. CAGWOA's performance is validated through experiments on various benchmark function test sets. Furthermore, we apply CAGWOA alongside similar methods in a multi-threshold image segmentation model for comparative experiments on lung X-ray images of infected patients. The results demonstrate CAGWOA's superiority, including better image detail preservation, clear segmentation boundaries, and adaptability across different threshold levels.

Abstract With the continuous development of the economy and society, along with the sustained population growth, the issue of water resources carrying capacity in China has attracted increasing attention. This paper constructs a model for evaluating the provincial water resources carrying capacity in China from four dimensions: water, economy, society, and ecology. Utilizing this model, we analyze the spatiotemporal variations in water resources carrying capacity among 31 provinces in China from 2005 to 2021. Additionally, we delve into the coupling coordination and influencing factors of water resources carrying capacity. The study reveals an overall increasing trend in China’s water resources carrying capacity index, with the ecological indicator exhibiting the most significant growth while the water resources sub-indicator lags behind. There are notable regional differences, with higher water resources carrying capacity observed in the eastern coastal areas and relatively lower capacity in the western regions. The ecological criterion becomes a core factor constraining water resources carrying capacity from 2005 to 2015, gradually giving way to the prominence of the social criterion since 2015. The coordination degree is relatively higher in the eastern regions, more scattered in the western regions, and relatively stable in the central regions. Based on the research findings, a series of recommendations are proposed, including strengthening environmental protection policies, optimizing water resources management mechanisms, improving water use efficiency, and promoting economic structural diversification. These suggestions aim to facilitate the sustainable development of water resources carrying capacity in China.

Abstract China’s rural reform is reliant on farmers' cooperatives as a key organization vehicle. It plays an important role in promoting rural revitalization. Such as, realizing the organic connection between small farmers and agricultural modernization. This study used the nearest neighbor index and kernel density estimation to analyze the spatial distribution and structural characteristics of farmer cooperatives in Hunan Province. It revealed the spatial differentiation law of cooperatives. Also using geographical detectors to figure out the main factors that affect the spatial distribution. The results show that: ① Hunan Farmers Cooperatives show significant spatial agglomeration. The overall spatial distribution shows the spatial characteristics of "one core, one circle, and multiple points". And the spatial distribution pattern of "large agglomeration, finger-shaped radiation distribution". Among them, the distribution of provincial demonstration cooperatives is relatively balanced. ② Cooperatives in six types of industries, such as planting, forestry, and feeding, showed agglomeration distribution. Different industrial cooperatives spread out in different ways, such as in an anti-"L" shape, a dual-core shape, or a one-center area. ③ The 24 influence factors selected from the five dimensions of the natural environment, social economic basis, production basis, output capacity, and facility basis have high, general, and weak influence on cooperatives' spatial distribution. The development and distribution of cooperatives mainly depend on resource endowment, social and economic development level, and market dependence. The spatial distribution heterogeneity of different professional cooperatives is mainly affected by slope, per capita disposable income of rural residents, road density, and other factors. ④ The progression of farmer cooperatives in Hunan Province should prioritize high-quality development, emphasizing the need for innovative approaches and transformative strategies within rural industrial organizations. It is imperative to optimize the spatial distribution of cooperatives, strategically contributing to the establishment of a novel framework for modern agricultural development in Hunan Province. Additionally, there is a critical emphasis on spearheading collaborative initiatives among cooperatives of varied industrial types, aimed at fostering the integrated development of rural primary, secondary, and tertiary industries.

Abstract Soil sickness a severe problem in tobacco production, leading to soil-borne diseases and reduce in tobacco yield. This occurs as a result of the interaction between root exudates and rhizosphere microorganisms, which is however, little studied until now. By combining the field investigation and pot experiment, we found the output yield consistently decreased during the first 10 years of continuous cropping in a tobacco field, but increased at the 15th year (15Y). The root exudate and rhizosphere bacterial community was further analyzed to reveal the underlying mechanism of the suppressive soil formation. Root exudate of 15Y tobacco enriched in amino acids and derivatives, while depleted in the typical autotoxins including phenolic acids and alkaloids. This was correlated to the low microbial diversity in 15Y, but also the changes in community composition and topological properties of the co-occurrence network. Especially, the reduced autotoxins were associated with low Actinobacteria abundance, low network complexity and high network modularity, which significantly correlated with the recovered output yield in 15Y. This study revealed the coevolution of rhizosphere microbiota and root exudate as the soil domesticated by continuous cropping of tobacco, and indicated a potential role of the autotoxins and theirs effect on the microbial community in the formation of suppressive soil.

Abstract Inflammation and fibrosis often occur in the kidney after acute injury, resulting in chronic kidney disease and consequent renal failure. Recent studies have indicated that lymphangiogenesis can drive renal inflammation and fibrosis in injured kidneys. However, whether and how this pathogenesis affects the contralateral kidney remain largely unknown. In our study, we uncovered a mechanism by which the contralateral kidney responded to injury. We found that the activation of mineralocorticoid receptors and the increase in vascular endothelial growth factor C in the contralateral kidney after unilateral ureteral obstruction could promote lymphangiogenesis. Furthermore, mineralocorticoid receptor activation in lymphatic endothelial cells resulted in the secretion of myofibroblast markers, thereby contributing to renal fibrosis. We observed that this process could be attenuated by administering the mineralocorticoid receptor blocker eplerenone, which, prevented the development of fibrotic injury in the contralateral kidneys of rats with unilateral ureteral obstruction. These findings offer valuable insights into the intricate mechanisms underlying kidney injury and may have implications for the development of therapeutic strategies to mitigate renal fibrosis in the context of kidney disease.

Abstract Modern medicine has produced large genetic datasets of high dimensions through advanced gene sequencing technology, and processing these data is of great significance for clinical decision-making. Gene selection (GS) is an important data preprocessing technique that aims to select a subset of feature information to improve performance and reduce data dimensionality. This study proposes an improved wrapper GS method based on forensic-based investigation (FBI). The method introduces the search mechanism of the slime mould algorithm in the FBI to improve the original FBI; the newly proposed algorithm is named SMA_FBI; then GS is performed by converting the continuous optimizer to a binary version of the optimizer through a transfer function. In order to verify the superiority of SMA_FBI, experiments are first executed on the 30-function test set of CEC2017 and compared with 10 original algorithms and 10 state-of-the-art algorithms. The experimental results show that SMA_FBI is better than other algorithms in terms of finding the optimal solution, convergence speed, and robustness. In addition, BSMA_FBI (binary version of SMA_FBI) is compared with 8 binary algorithms on 18 high-dimensional genetic data from the UCI repository. The results indicate that BSMA_FBI is able to obtain high classification accuracy with fewer features selected in GS applications. Therefore, SMA_FBI is considered an optimization tool with great potential for dealing with global optimization problems, and its binary version, BSMA_FBI, can be used for GS tasks.

Abstract This study aimed to predict the outcome of patient specific quality assurance (PSQA) in IMRT for breast cancer using complexity metrics, such as MU factor, MAD, CAS, MCS. Several breast cancer plans were considered, including LBCS, RBCS, LBCM, RBCM, left breast, right breast and the whole breast for both Edge and TrueBeam LINACS. Dose verification was completed by Portal Dosimetry (PD). The receiver operating characteristic (ROC) curve was employed to determine whether the treatment plans pass or failed. The area under the curve (AUC) was used to assess the classification performance. The correlation of PSQA and complexity metrics was examined using Spearman’s rank correlation coefficient (R s ). For LINACS, the most suitable complexity metric was found to be the MU factor (Edge R s = − 0.608, p

Abstract Two OR3 research vessel cruises were conducted at seven nearshore sites from north to south in the western coastal waters off Taiwan in May (late spring) and November (late autumn) 2019 in order to gain insights into the 2 °C difference in the tropical-subtropical fish fauna. Totally, 37 families, 72 genera, and 99 taxas were recorded for the 1809 fishes. Three fish assemblages, the North, South, and Fall-Zhuoshui River (ZRf) groups, were identified as eurythermal, stenothermal, and croaker communities. Their dominants, in rank order, were Tarphops oligolepis, Liachirus melanospilosa, Ostorhinchus fasciatus, and Trachinocephalus myops for the Northern eurythermal group, Arnoglossus tenuis, Eubleekeria splendens, and Ostorhinchus pleuron for the Southern stenothermal group, and Johnius taiwanensis, Chrysochir aureus, and Pennahia macrocephalus for the croaker-ZRf group. Their distribution was markedly correlated with the bottom water temperature, seafloor grain size, and concentration of suspended solids. The influence of a 2 °C difference on the tropical and subtropical demersal fish could indicate how rising temperatures due to climate change are shaping fish communities. The flatfish, Liachirus melanospilos, was distributed northward by 0.5oN and is suggested to be considered as an ecological indicator of the tropicalization of subtropical marine ecosystems in the future.

Abstract Peierls transition that modifies electronic band structure has attracted intensive attention in solid state physics. In the present work, we report that a photonic analog of Peierls transition has been observed in a 1-D triangular metal diaphragm array, where the photonic bandgap structures have been designed at will by adjusting periodically metal diaphragm positions. It is shown by the numerical analysis that the transmission and radiation effect of the present periodic metal structure designed through the Peierls transition rule exhibits the behavior significantly different from an original periodic structure with each unit cell containing a metal diaphragm. The near- and far-field measurement results are in good agreement with our theoretical simulation. The present effect of photonic Peierls transition can serve as a working mechanism for designing new types of guided wave devices. It can be seen that the photonic Peierls transition would be one of the simplest ways for modifying the transport characteristics of electromagnetic waves in periodic structures.

Abstract Oxidative stress has been shown to induce cell death in a wide range of human diseases including cardiac ischemia/reperfusion injury, drug induced cardiotoxicity, and heart failure. However, the mechanism of cell death induced by oxidative stress remains incompletely understood. Here we provide new evidence that oxidative stress primarily induces ferroptosis, but not apoptosis, necroptosis, or mitochondria-mediated necrosis, in cardiomyocytes. Intriguingly, oxidative stress induced by organic oxidants such as tert-butyl hydroperoxide (tBHP) and cumene hydroperoxide (CHP), but not hydrogen peroxide (H2O2), promoted glutathione depletion and glutathione peroxidase 4 (GPX4) degradation in cardiomyocytes, leading to increased lipid peroxidation. Moreover, elevated oxidative stress is also linked to labile iron overload through downregulation of the transcription suppressor BTB and CNC homology 1 (Bach1), upregulation of heme oxygenase 1 (HO-1) expression, and enhanced iron release via heme degradation. Strikingly, oxidative stress also promoted HO-1 translocation to mitochondria, leading to mitochondrial iron overload and lipid reactive oxygen species (ROS) accumulation. Targeted inhibition of mitochondrial iron overload or ROS accumulation, by overexpressing mitochondrial ferritin (FTMT) or mitochondrial catalase (mCAT), respectively, markedly inhibited oxidative stress-induced ferroptosis. The levels of mitochondrial iron and lipid peroxides were also markedly increased in cardiomyocytes subjected to simulated ischemia and reperfusion (sI/R) or the chemotherapeutic agent doxorubicin (DOX). Overexpressing FTMT or mCAT effectively prevented cardiomyocyte death induced by sI/R or DOX. Taken together, oxidative stress induced by organic oxidants but not H2O2 primarily triggers ferroptotic cell death in cardiomyocyte through GPX4 and Bach1/HO-1 dependent mechanisms. Our results also reveal mitochondrial iron overload via HO-1 mitochondrial translocation as a key mechanism as well as a potential molecular target for oxidative stress-induced ferroptosis in cardiomyocytes.

Abstract So far, coal, petroleum, and natural gas are still the most widely used fuels, and the emissions of SO2, NOX and particulate matter produced from their combustion have a serious influence on the air. Therefore, it is necessary to develop a clean fuel. In this study, the bulk curing barns were equipped with different fuel equipment, Barn A used traditional coal heating equipment; Barn B used biomass briquettes fuel (BBF) integrated heating equipment; Barn C equipped with alcohol-based fuel (ABF) heating equipment. The temperature of the outer surface of the heating equipment, the exhaust gas of the chimney, and the curing heat efficiency and energy consumption were analyzed. Compared with the barn BBF and barn coal, the barn ABF can meet the flue-cured tobacco curing highest temperature requirements of 68 °C, the accuracy of the target dry bulb temperature (DBT) curve during the curing of flue-cured tobacco was 93.4%. At the same time, during ABF combustion, the emissions of CO2 and CO were 40.82% and 0.19%, respectively. However, no emissions of NOX, SO2, and H2S were detected in the chimney exhaust. Compared with the barn BBF and barn coal, the thermal efficiency of barn ABF heating equipment in the barn was increased by 44.78% and 86.28%, respectively. Additionally, the coast per kilogram of dry tobacco was reduced by 19.44% and 45.28%, respectively. Therefore, compared to barn coal and barn BBF, the barn ABF can control temperature changes more accurately, and shows an obvious advantage in environmental protection and heat utilization efficiency.

Abstract To investigate the mechanical properties of fractured dolomite, this study analyzed the fracture characteristics (dip angle, length, position, quantity) using the Pearson coefficient and MIC coefficient. Subsequently, the data pertaining to fracture characteristics is preprocessed using a third-degree polynomial, and a three-classification strategy is implemented to improve the logistic regression algorithm to establish the strength prediction model of fractured dolomite. Furthermore, the significance order of the impact of fracture characteristics on rock strength was determined using the numerical simulation software PFC3D, and the dip angle effect was explained from the perspective of internal fracture propagation within the rock. The results show that: (1) When the regularization coefficient λ = 10,000, the algorithm has the highest prediction accuracy and the strongest model generalization ability. (2) The numerical simulation analysis software PFC3D can accurately invert rock failure process and characteristics, and the order of influence of fracture characteristics on rock strength is dip angle > length > position.

Abstract We previously confirmed that a strain of Lactobacillus oris isolated from the fecal samples of healthy Hainan centenarian having potent lipid-lowering ability in HepG2 cells; and this study was to investigate the effect of the stain on non-alcoholic fatty liver in mice in vivio. The Lactobacillus oris strain isolated from Hainan centenarian fecal samples were frozen stored in our laboratory. Thirty ob/ob mice (10 in each group) were orally gavaged with Lactobacillus oris (Lactobacillus, 5 × 109 cfu), mixed probiotics (Mixed, 5 × 109 cfu, a mixture with known lipid-lowering ability), or culture medium (Control) respectively. Lactobacillus oris isolated from fecal samples of Hainan centenarians showed significantly in vivo lipid lowering ability compared with the controls, and the ability was comparable with mixed probiotics strains in mice The possible mechanisms of lipid-lowering of probiotics and Lactobacillus oris may be associated with HMGR inhibition to suppress the synthesis of endogenous cholesterol; bile acids reabsorption, and intestinal FXR-FGF15 signaling pathways promoting the cholesterol conversion into bile acids secretion.

Abstract The saltwater hard clam Mercenaria mercenaria (M. mercenaria) as a representative of low-value shellfish, enhancing its flavor quality, is the key to enter the high-end market. Nevertheless, there has not been reported research on the flavor quality of M. mercenaria. This study compared the flavor quality of selective and non-selective saltwater hard clams of M. mercenaria by using various indicators: proximate component, free amino acids, nucleotides, and metabolomic analysis. The results indicated that selective breeding contributed to the significant improvement contents of crude protein, flavor-associated free amino acids (glutamic acid, aspartic acid, proline, etc.), and nucleotides (AMP) (P 1 and P

Abstract Tuberculosis (TB) is a prevalent disease causing an estimated 1.6 million deaths and 10.6 million new cases annually. Discriminating TB disease from differential diagnoses can be complex, particularly in the field. Increased levels of complement component C1q in serum have been identified as a specific and accessible biomarker for TB disease but the source of C1q in circulation has not been identified. Here, data and samples previously collected from human cohorts, a clinical trial and a non-human primate study were used to identify cells producing C1q in circulation. Cell subset frequencies were correlated with serum C1q levels and combined with single cell RNA sequencing and flow cytometry analyses. This identified monocytes as C1q producers in circulation, with a pronounced expression of C1q in classical and intermediate monocytes and variable expression in non-classical monocytes.

Abstract Transportation stress is one of the most serious issues in the management of yak. Previous studies have demonstrated that transport stress is caused by a pro-oxidant state in the animal resulting from an imbalance between pro-oxidant and antioxidant status. In this context, vitamin C has the ability to regulate reactive oxygen species (ROS) synthesis and alleviate oxidative stress. Although this effect of vitamin C is useful in pigs, goats and cattle, the effect of vitamin C on the mitigation of transport stress in yaks is still unclear. The purpose of this study was to better assess the metabolic changes induced by the action of vitamin C in yaks under transportation stress, and whether these changes can influence antioxidant status. After the yaks arrived at the farm, control or baseline blood samples were collected immediately through the jugular vein (VC_CON). Then, 100 mg/kg VC was injected intramuscularly, and blood samples were collected on the 10th day before feeding in the morning (VC). Relative to the control group, the VC injection group had higher levels of VC. Compared with VC_CON, VC injection significantly (P 0.05) in GGT, ALP, TBA, TP, ALBII, GLO, A/G, TC, TG, HDL-C, LDL-C, GLU and l-lactate between VC_CON and VC. The injection of VC led to greater (P 0.05) the serum concentrations of LPO and ROS. The injection of VC led to greater (P 0.05) in GSH, GSH-ST and GR was observed between VC_CON and VC. Compared with the control group, metabolomics using liquid chromatography tandem–mass spectrometry identified 156 differential metabolites with P 1.5 in the VC injection group. The injection of VC resulted in significant changes to the intracellular amino acid metabolism of glutathione, glutamate, cysteine, methionine, glycine, phenylalanine, tyrosine, tryptophan, alanine and aspartate. Overall, our study indicated that VC injections were able to modulate antioxidant levels by affecting metabolism to resist oxidative stress generated during transport.

Abstract In this study, we explored inter-ocular asymmetry (between the two eyes of the same patient) using optical coherence tomography angiography (OCTA) in patients with diabetes mellitus (DM) at different retinopathy stages. A total of 258 patients were divided into four groups: no DM, DM without diabetic retinopathy (DR), non-proliferative DR (NPDR), and proliferative DR (PDR). Superficial and deep vessel density (SVD, DVD), superficial and deep perfusion density (SPD, DPD), foveal avascular zone (FAZ) area, perimeter and circularity were calculated, and asymmetry index (AI) was used to evaluate the asymmetry of two eyes of the same subject. AIs of SPD, SVD, FAZ area and FAZ perimeter in the PDR group were larger than all other 3 groups (all p

Abstract “”We employed radiomics and clinical features to develop and validate a preoperative prediction model to estimate the omental metastases status of locally advanced gastric cancer (LAGC). A total of 460 patients (training cohort, n = 250; test cohort, n = 106; validation cohort, n = 104) with LAGC who were confirmed T3/T4 stage by postoperative pathology were continuously collected retrospectively, including clinical data and preoperative arterial phase computed tomography images (APCT). Dedicated radiomics prototype software was used to segment the lesions and extract features from the preoperative APCT images. The least absolute shrinkage and selection operator (LASSO) regression was used to select the extracted radiomics features, and a radiomics score model was constructed. Finally, a prediction model of omental metastases status and a nomogram were constructed combining the radiomics scores and selected clinical features. An area under the curve (AUC) of the receiver operating characteristic curve (ROC) was used to validate the capability of the prediction model and nomogram in the training cohort. Calibration curves and decision curve analysis (DCA) were used to evaluate the prediction model and nomogram. The prediction model was internally validated by the test cohort. In addition, 104 patients from another hospital's clinical and imaging data were gathered for external validation. In the training cohort, the combined prediction (CP) model (AUC 0.871, 95% CI 0.798–0.945) of the radiomics scores combined with the clinical features, compared with clinical features prediction (CFP) model (AUC 0.795, 95% CI 0.710–0.879) and radiomics scores prediction (RSP) model (AUC 0.805, 95% CI 0.730–0.879), had the better predictive ability. The Hosmer–Lemeshow test of the CP model showed that the prediction model did not deviate from the perfect fitting (p = 0.893). In the DCA, the clinical net benefit of the CP model was higher than that of the CFP model and RSP model. In the test and validation cohorts, the AUC values of the CP model were 0.836 (95% CI 0.726–0.945) and 0.779 (95% CI 0.634–0.923), respectively. The preoperative APCT-based clinical-radiomics nomogram showed good performance in predicting omental metastases status in LAGC, which may contribute to clinical decision-making.

Abstract The prognostic value of albumin-to-alkaline phosphatase ratio (AAPR) in patients with hepatocellular carcinoma (HCC) remains controversial. This meta-analysis aims to evaluate the prognostic role of AAPR in patients with HCC. The databases of Web of Science, Embase, Cochrane Library and PubMed were comprehensively searched from inception to April 25, 2022. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated with Stata 16.0 software for the assessment of the relationship between AAPR and overall survival (OS) as well as recurrence-free survival (RFS) in patients with HCC. A total of 2634 patients from 12 cohorts were included in this meta-analysis. The pooled results showed that lower AAPR predicted poorer OS (HR 2.02, 95% CI 1.78–2.30). Similarly, pooled results demonstrated that lower AAPR also predicted poorer RFS (HR 1.88, 95% CI 1.37–2.57). The heterogeneity for RFS by multivariate analytic results and the publication bias for OS existed, however, the subgroup analysis, meta-regression analysis as well as adjustment using trim-and-fill analysis confirmed an association between AAPR and OS as well as RFS. This meta-analysis proves that lower AAPR in patients with HCC predicted inferior survival outcomes, and AAPR might be a promising indicator for the prognosis of HCC.

Abstract Constraining the stress related to lithospheric deformation in natural rocks is key to develop and test a geodynamic model. However, the cautions of extrapolating piezometers that are established on experimental samples to natural rocks are less addressed. In this study, we investigated the microstructures of a natural harzburgite sample using the electron backscatter diffraction (EBSD) technique. Subgrain boundary (SGB) geometries suggest large percentages of (010)[100] and {0kl}[100] dislocation slip systems in olivines. More importantly, multiple low-angle misorientation boundaries (LAMBs) variants are recognized for the first time in olivine based on their distinctive characteristics with the change of EBSD mapping step size. The LAMBs that exist at a small step size (≤ 1 μm) are mostly equivalent to real SGBs, while other LAMBs that appear only when the step size is larger (> 1 μm) are artificial SGBs. Besides, the former develop mainly in the high LAMB density grains, whereas the latter are mostly found in the low LAMB density grains. This result reinforces the previous knowledge that the stress calculated using subgrain-related piezometers is meaningful only when real SGBs are captured at sufficiently small step size. Furthermore, we provide a proof of concept that SGB density and kernel average misorientation (KAM) are two viable metrics to estimate stress. These two alternative piezometers, which still need calibrations using the experimentally deformed samples, are anticipated to have wide applications in natural rocks.

Abstract Urban development continues to face the dilemma of spatial inequality of public facilities, particularly educational and medical facilities. Identifying inequalities in various types of public facilities and their driving mechanisms is crucial in reducing social inequality. However, information on this topic is limited. This study took 10 typical cities in China as cases. We used the methods of the Gini coefficient and hedonic price model as bases in evaluating the equality of nine types of education and medical facilities, focusing on the differences between urban and rural areas. Moreover, we further analyzed the driving factors of facility equality. Results showed that equality of public facilities in urban areas was significantly higher than that in rural areas. Primary schools, middle schools, and health service centers were relatively equal, and kindergartens and pharmacies were unequal only in rural areas. However, the equality of facilities with large-size or commercial attributes was not optimistic. Furthermore, there remained a significant gap among counties (or districts), which was mainly driven by population, economy, and building density in the form of logarithm and logarithmic linear models. Our research contributes to an in-depth understanding of the inequality of public facilities and further supports decision-making to improve social equality.

Abstract Tourniquet use always carries potential risks, which can range from mild transient functional impairments of thigh pain, skin blisters to severe permanent dysfunction of limb paralysis, nerve injuries or compartment syndrome. The ideal method for minimizing intraoperative tourniquet pressure (TP) for reducing postoperative complications remains controversial. In this prospective, randomized and controlled study, we reinvestigated an estimation formula for TP based on thigh circumferences and systolic blood pressure (SBP) with two traditional methods for TP determination in total knee arthroplasty (TKA): SBP plus 100 mmHg and a fixed value of 300 mmHg. TP values and postoperative thigh pain scores were compared among three groups. The intraoperative TP value of the formula-calculated group was lower than that of the traditional groups (14.7 mmHg, P = 0.3475 and 94.7 mmHg, P

Abstract Pulmonary tuberculosis (PTB) is a major health issue in Northwest China. Most previous studies on the spatiotemporal patterns of PTB considered all PTB cases as a whole; they did not distinguish notified bacteriologically positive PTB (BP-PTB) and notified bacteriologically negative PTB (BN-PTB). Thus, the spatiotemporal characteristics of notified BP-PTB and BN-PTB are still unclear. A retrospective county-level spatial epidemiological study (2011–2018) was conducted in Shaanxi, Northwest China. In total, 44,894 BP-PTB cases were notified, with an average annual incidence rate of 14.80 per 100,000 persons between 2011 and 2018. Global Moran’s I values for notified BP-PTB ranged from 0.19 to 0.49 (P

Abstract Autotomy appendages are fundamental evolutionary adaptations to escape predation. The siphon is an important foraging organ for bivalves. Here, we report the first demonstration of autotomy of the siphon in marine bivalves (razor clam Solen grandis) and the effect of siphonal autotomy in S. grandis on foraging and metabolic characteristics. In this study, the feeding rate and digestive enzyme activities upon siphonal autotomy in razor clams were investigated. Moreover, endogenous metabolites pre/post-autotomy of the siphon were investigated using liquid chromatography tandem-mass spectrometry (LC–MS). The feeding rate and digestive enzyme activities decreased significantly after siphonal autotomy in S. grandis (P

Abstract The aim of this study was to evaluate the effectiveness and safety of AngioJet rheolytic thrombectomy among patients with high thrombus burden. Routine manual thrombus aspiration in patients with ST-segment elevation myocardial infarction (STEMI) does not improve clinical outcomes and was associated with an increased rate of stroke. However, the safety of mechanical thrombus aspiration is still unknown. This was a retrospective, single-center study involving 621 patients with Thrombolysis In Myocardial Infarction thrombus grade 5. The primary outcome was the composite of major adverse cardiovascular events (MACE) within 12 months. The safety outcome was stroke within 1-year. Propensity matching score was calculated due to the significant baseline differences between the AngioJet rhelytic thrombectomy group and the routine treatment group. AngioJet rheolytic thrombectomy was performed in 117 patients. After propensity-score matching, there was no significant difference both in the incidence of MACE (11.1% vs 17.9%, hazard ratio, 1.641; 95% confidence interval [CI] 0.822 to 3.277, p = 0.161) and the incidences of stroke (1.7% vs 2.6%, hazard ratio 1.522; 95% confidence interval [CI] 0.254 to 9.107, p = 0.646) between two groups at 1-year follow-up. In patients with Thrombolysis In Myocardial Infarction thrombus grade 5, AngioJet rheolytic thrombectomy did not improve clinical outcomes at 1 year. However, AngioJet rheolytic thrombectomy did not increase the risk of stroke in patients with high thrombus burden.

Abstract Radioactive aerosols harmful to humans are often produced in nuclear accidents, and their source term characteristics (total volume and particle size distribution) and dispersion patterns have important implications for accident response and hazard assessment. However, experimental studies of radioactive aerosols cannot be directly conducted in open space due to the hazardous nature of radioactive aerosols. In this study, silver was used instead of plutonium to study the aerosol source term under different specific internal energy inputs (SIEI) to simulate a low order explosion in an accident. Results show that aerosol release fraction (ARF) and respirable release fraction (RRF) of silver increase linearly with SIEI first, then varies in a range of 8% ~ 19%, with a turning point at SIEI of 1.4 MJ/kg. Analysis suggests an increase of difference between ARF and RRF with respect to SIEI. The size distribution of silver aerosol around 10 µm is influenced by SIEI significantly, which could be possibly attributed to the interactions between silver aerosol and ambient aerosol (solid HE products or rust). Comparison between the source term of silver and plutonium suggests that silver is a good surrogate of plutonium in studying aerosol for SIEI of MJ/kg level.

Abstract Despite many studies on the influence of cropping practices on soil microbial community structure, little is known about ecological patterns of rare and abundant microbial communities in response to different tobacco cropping systems. Here, using the high-throughput sequencing technique, we investigated the impacts of two different cropping systems on soil biochemical properties and the microbial community composition of abundant and rare taxa and its driving factors in continuous and rotational tobacco cropping systems in the mountain lands of Yunnan, China. Our results showed that distinct co-occurrence patterns and driving forces for abundant and rare taxa across the different cropping systems. The abundant taxa were mainly constrained by stochastic processes in both cropping systems. In contrast, rare taxa in continuous cropping fields were mainly influenced by environmental perturbation (cropping practice), while governed by deterministic processes under rotational cropping. The α-diversity indices of rare taxa tended to be higher than those of the abundant ones in the two cropping systems. Furthermore, the network topologies of rare taxa were more complex than those of the abundant taxa in the two cropping systems. These results highlight that rare taxa rather than abundant ones play important roles in maintaining ecosystem diversity and sustaining the stability of ecosystem functions, especially in continuous cropping systems.

Abstract Periodontitis, one of the most common chronic inflammatory diseases, affects the quality of life. Osteogenesis plays an important role in the disease. There is a connection between hydrogen sulfide (H2S) and periodontitis, but according to the study has been published, the precise role of H2S in inflammation remains in doubt. The main reason for the lack of research is that H2S is an endogenous gasotransmitter, difficult to discern through testing. So, we synthesized a novel fluorescence probe which can detect H2S in vitro. By using the novel H2S fluorescence probe, we found that H2S changes in osteoblasts mainly by cystathionine-γ-lyase, and H2S increases under LPS stimulation. H2S could be a potential marker for diagnosis of inflammatory diseases of bone, and might help deepen studies of the changes of H2S level and promote the progression on the researches about pathogenesis of periodontitis.

Abstract To retrospectively analyze the use of artificial pneumoperitoneum in CT scans, to explore its operation methods and technical points, and to lay the foundation for the widespread application of artificial pneumoperitoneum in CT. A total of 331 patients who underwent artificial pneumoperitoneum with CT angiography from January 1, 2013, to November 1, 2019, were recruited. All patients underwent standardized artificial pneumoperitoneum in the horizontal, left and right lateral, and prone positions during CT thin-layer scans of the abdomen and 3D reconstruction. Taking the surgical results as the gold standard, and using kappa test to verify the consistency of surgical results and imaging results. In all 331 patients, 43 patients had a normal peritoneal space, and 288 patients had an abnormal peritoneal space. And only 22 patients developed complications of subcutaneous emphysema, accounting for 6.6% of all 331 patients. In terms of the postoperative results, 28 were normal, and 303 were abnormal. The sensitivity, specificity and accuracy of CT diagnosis of abdominal adhesions using artificial pneumoperitoneum were 100%, 95.04%, and 95.46%, respectively. According to the Kappa consistency test, the imaging diagnosis from the CT scan with artificial pneumoperitoneum had a high consistency with the surgical results (kappa = 0.796, P

Abstract This study is the first multi-center non-inferiority study that aims to critically evaluate the effectiveness of HHUS/ABUS in China breast cancer detection. This was a multicenter hospital-based study. Five hospitals participated in this study. Women (30–69 years old) with defined criteria were invited for breast examination by HHUS, ABUS or/and mammography. For BI-RADS category 3, an additional magnetic resonance imaging (MRI) test was provided to distinguish the true negative results from false negative results. For women classified as BI-RADS category 4 or 5, either core aspiration biopsy or surgical biopsy was done to confirm the diagnosis. Between February 2016 and March 2017, 2844 women signed the informed consent form, and 1947 of them involved in final analysis (680 were 30 to 39 years old, 1267 were 40 to 69 years old).For all participants, ABUS sensitivity (91.81%) compared with HHUS sensitivity (94.70%) with non-inferior Z tests, P = 0.015. In the 40–69 age group, non-inferior Z tests showed that ABUS sensitivity (93.01%) was non-inferior to MG sensitivity (86.02%) with P

Abstract A novel coronavirus (SARS-CoV-2) has spread worldwide and led to high disease burden around the world. This study aimed to explore the key parameters of SARS-CoV-2 infection and to assess the effectiveness of interventions to control the coronavirus disease 2019 (COVID-19). A susceptible—exposed—infectious—asymptomatic—recovered (SEIAR) model was developed for the assessment. The information of each confirmed case and asymptomatic infection was collected from Ningbo Center for Disease Control and Prevention (CDC) to calculate the key parameters of the model in Ningbo City, China. A total of 157 confirmed COVID-19 cases (including 51 imported cases and 106 secondary cases) and 30 asymptomatic infections were reported in Ningbo City. The proportion of asymptomatic infections had an increasing trend. The proportion of elder people in the asymptomatic infections was lower than younger people, and the difference was statistically significant (Fisher’s Exact Test, P = 0.034). There were 22 clusters associated with 167 SARS-CoV-2 infections, among which 29 cases were asymptomatic infections, accounting for 17.37%. We found that the secondary attack rate (SAR) of asymptomatic infections was almost the same as that of symptomatic cases, and no statistical significance was observed (χ 2 = 0.052, P = 0.819) by Kruskal–Wallis test. The effective reproduction number (R eff ) was 1.43, which revealed that the transmissibility of SARS-CoV-2 was moderate. If the interventions had not been strengthened, the duration of the outbreak would have lasted about 16 months with a simulated attack rate of 44.15%. The total attack rate (TAR) and duration of the outbreak would increase along with the increasing delay of intervention. SARS-CoV-2 had moderate transmissibility in Ningbo City, China. The proportion of asymptomatic infections had an increase trend. Asymptomatic infections had the same transmissibility as symptomatic infections. The integrated interventions were implemented at different stages during the outbreak, which turned out to be exceedingly effective in China.

Abstract Lung squamous cell carcinoma (LUSC) is a common type of lung cancer with high incidence and mortality rate. Tumor mutational burden (TMB) is an emerging biomarker for selecting patients with non-small cell lung cancer (NSCLC) for immunotherapy. This study aimed to reveal TMB involved in the mechanisms of LUSC and develop a model to predict the overall survival of LUSC patients. The information of patients with LUSC were obtained from the cancer genome atlas database (TCGA). Differentially expressed genes (DEGs) between low- and the high-TMB groups were identified and taken as nodes for the protein–protein interaction (PPI) network construction. Gene oncology (GO) enrichment analysis and gene set enrichment analysis (GSEA) were used to investigate the potential molecular mechanism. Then, we identified the factors affecting the prognosis of LUSC through cox analysis, and developed a risk score signature. Kaplan–Meier method was conducted to analyze the difference in survival between the high- and low-risk groups. We constructed a nomogram based on the risk score model and clinical characteristics to predict the overall survival of patients with LUSC. Finally, the signature and nomogram were further validated by using the gene expression data downloaded from the Gene Expression Omnibus (GEO) database. 30 DEGs between high- and low-TMB groups were identified. PPI analysis identified CD22, TLR10, PIGR and SELE as the hub genes. Cox analysis indicated that FAM107A, IGLL1, SELE and T stage were independent prognostic factors of LUSC. Low-risk scores group lived longer than that of patients with high-risk scores in LUSC. Finally, we built a nomogram that integrated the clinical characteristics (TMN stage, age, gender) with the three-gene signature to predict the survival probability of LUSC patients. Further verification in the GEO dataset. TMB might contribute to the pathogenesis of LUSC. TMB-associated genes can be used to develope a model to predict the OS of lung squamous cell carcinoma patients.

Abstract It’s vital to explore critical indicators when identifying potential pollution sources of urban rivers. However, the variations of urban river water qualities following temporal and spatial disturbances were highly local-dependent, further complicating the understanding of pollution emission laws. In order to understand the successional trajectory of water qualities of urban rivers and the underlying mechanisms controlling these dynamics at local scale, we collected daily monitoring data for 17 physical and chemical parameters from seven on-line monitoring stations in Nanfeihe River, Anhui, China, during the year 2018. The water quality at tributaries were similar, while that at main river was much different. A seasonal ‘’turning-back” pattern was observed in the water quality, which changed significantly from spring to summer but finally changed back in winter. This result was possibly regulated by seasonally-changed dissolved oxygen and water temperature. Linear mixed models showed that the site 2, with the highest loads of pollution, contributed the highest (β = 0.316, P

Abstract With the rapid increase in HIV prevalence of men who have sex with men (MSM) in recent years and common human migration and travelling across different provinces in China, MSM are now finding it easier to meet each other, which might contribute to local HIV epidemics as well as fueling cross-province transmission. We performed a cross-sectional survey in 2018–2019 to investigate the current HIV subtype diversity and inferred HIV strain transmission origin among MSM in Guangxi province, China based on a phylogenetic analysis. Based on 238 samples, we found that the HIV-1 subtype diversity was more complicated than before, except for three major HIV subtypes/circulating recombinant forms (CRFs): CRF07_BC, CRF01_AE, CRF55_01B, five other subtypes/CRFs (CRF59_01B, B, CRF08_BC, CRF67_01B, CRF68_01B) and five unique recombinant forms (URFs) were detected. In total, 76.8% (169/220) of samples were infected with HIV from local circulating strains, while others originated from other provinces, predominantly Guangdong and Shanghai. The high diversity of HIV recombinants and complicated HIV transmission sources in Guangxi MSM indicates that there has been an active sexual network between HIV positive MSM both within and outside Guangxi without any effective prevention. Inter-province collaboration must be enforced to provide tailored HIV prevention and control services to MSM in China.

Abstract The purpose of the study is to explore the effect of flue-curing procedure on the diversity of microbial communities in tobaccos and the dynamic change of compositions of microbial communities in the flue-curing process. It expects to provide a theoretical basis for the application of microbes in tobacco leaves and a theoretical basis and idea for optimization of the flue-curing technologies. By investigating tobacco variety K326, the tests were carried out for comparing the conventional flue-curing procedure and dry-ball temperature set and wet-ball temperature degradation flue-curing procedure. Based on the culture-independent approach and high-throughput sequencing procedure, the relationship between the flue-curing procedure for tobaccos and microbial communities in tobaccos was revealed by measuring the dynamic change of microbial communities. The results indicated that:(1) Relative to surface wiping method, washing method was more suitable for the sampling of microbes on the surface of tobacco leaves; (2) Dry-ball temperature set and wet-ball temperature degradation flue-curing procedure was more favorable for maintaining the microbial diversity of tobaccos; (3) Relative to bacteria of the tobaccos, the succession rule of the fungal communities in tobaccos was relatively steady; (4)Compared with bacterial community diversity, the fungal community diversity presented an obvious negative correlation with temperature and humidity during the flue-curing process. (5) The function of bacterial communities in tobaccos matched with the material transformation law of tobaccos, having a direct correlation on the flue-curing process. In short, Dry-ball temperature set and wet-ball temperature degradation flue-curing procedure can more favorably maintain the microbial diversity of tobaccos; moreover, the function of the tobacco system involved in microbes in tobaccos was closely related to the material transformation law of tobaccos in the flue-curing process. It validated that the bacteria in tobaccos play an important role in the flue-curing process of tobaccos.

Abstract Identifying drug-target interaction (DTI) candidates is crucial for drug repositioning. However, usually only positive DTIs are deposited in known databases, which challenges computational methods to predict novel DTIs due to the lack of negative samples. To overcome this dilemma, researchers usually randomly select negative samples from unlabeled drug-target pairs, which introduces a lot of false-positives. In this study, a negative sample extraction method named NDTISE is first developed to screen strong negative DTI examples based on positive-unlabeled learning. A novel DTI screening framework, PUDTI, is then designed to infer new drug repositioning candidates by integrating NDTISE, probabilities that remaining ambiguous samples belong to the positive and negative classes, and an SVM-based optimization model. We investigated the effectiveness of NDTISE on a DTI data provided by NCPIS. NDTISE is much better than random selection and slightly outperforms NCPIS. We then compared PUDTI with 6 state-of-the-art methods on 4 classes of DTI datasets from human enzymes, ion channels, GPCRs and nuclear receptors. PUDTI achieved the highest AUC among the 7 methods on all 4 datasets. Finally, we validated a few top predicted DTIs through mining independent drug databases and literatures. In conclusion, PUDTI provides an effective pre-filtering method for new drug design.

Abstract Cancer stem cells play an important role on tumor progression. Biomarkers of stem cell property and their relationship to extranodal involvement of malignant lymphocytes are undefined in diffuse large B-cell lymphoma (DLBCL). Here we showed that junctional adhesion molecule-A (JAM-A) was highly expressed in DLBCL patients with multiple extranodal lesions. JAM-A maintained B-lymphoma cell stemness and was associated with cell invasion and epithelial-to-mesenchymal transition both in vitro and in vivo. As mechanism of action, JAM-A overexpression selectively activated transforming growth factor-β (TGF-β)/NODAL signaling, thereby enhanced B-lymphoma cell aggressiveness and induced extranodal involvement to mesoendoderm-derived organs in DLBCL. Lenalidomide downregulated JAM-A and downstream NODAL expression, resulting in inhibition of B-lymphoma cell invasion and epithelial-to-mesenchymal transition. In a murine xenograft model established with subcutaneous injection of JAM-A-overexpressing B-lymphoma cells, lenalidomide retarded tumor growth and prevented cell invasion to mesoendoderm-derived organs, consistent with the downregulation of JAM-A and NODAL expression. Collectively, these findings indicated that JAM-A was related to extranodal involvement in DLBCL through modulating TGF-β/NODAL signaling. Identified as a biomarker of stem cell property, JAM-A indicated the sensitivity of B-lymphoma cells to lenalidomide. Therapeutic targeting of JAM-A/NODAL axis could thus be a promising clinical strategy to impede tumor progression in DLBCL.

Abstract The extensive environmental adaptability of the genus Paenibacillus is related to the enormous diversity of its gene repertoires. Paenibacillus sp. SSG-1 has previously been reported, and its agar-degradation trait has attracted our attention. Here, the genome sequence of Paenibacillus sp. SSG-1, together with 76 previously sequenced strains, was comparatively studied. The results show that the pan-genome of Paenibacillus is open and indicate that the current taxonomy of this genus is incorrect. The incessant flux of gene repertoires resulting from the processes of gain and loss largely contributed to the difference in genomic content and genome size in Paenibacillus. Furthermore, a large number of genes gained are associated with carbohydrate transport and metabolism. It indicates that the evolution of glycometabolism is a key factor for the environmental adaptability of Paenibacillus species. Interestingly, through horizontal gene transfer, Paenibacillus sp. SSG-1 acquired an approximately 150 kb DNA fragment and shows an agar-degrading characteristic distinct from most other non-marine bacteria. This region may be transported in bacteria as a complete unit responsible for agar degradation. Taken together, these results provide insights into the evolutionary pattern of Paenibacillus and have implications for studies on the taxonomy and functional genomics of this genus.

Abstract Current WHO guidelines recommend initiating ART regardless of CD4+ cell count. In response, we conducted an observational cohort study to assess the effects of pre-ART CD4+ cell count levels on death, attrition, and death or attrition in HIV treated patients. This large HIV treatment cohort study (n = 49,155) from 2010 to 2015 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between pre-ART CD4+ cell counts and death, attrition, and death or attrition. The average mortality and ART attrition rates among all treated patients were 2.63 deaths and 5.32 attritions per 100 person-years, respectively. Compared to HIV patients with 500 CD4+ cells/mm3 at ART initiation had a significantly lower mortality rate (Adjusted hazard ratio: 0.56, 95% CI: 0.40–0.79), but significantly higher ART attrition rate (AHR: 1.17, 95% CI: 1.03–1.33). Results from this study suggest that HIV patients with high CD4+ cell counts at the time of ART initiation may be at greater risk of treatment attrition. To further reduce ART attrition, it is imperative that patient education and healthcare provider training on ART adherence be enhanced and account for CD4 levels at ART initiation.

Abstract Symplekin is a multifunctional protein that localizes to both tight junctions and the nucleus in polarized epithelial cells, with confirmed roles in mRNA maturation, transcriptional modulation and tight-junction assembly. However, the mechanisms governing its subcellular distribution and related functions remain unclear. In this study, we found that symplekin primarily localizes to the nuclei of cultured dedifferentiated colorectal cancer cells, and nuclear symplekin showed higher phosphorylation and binding affinity with YBX3 than its membrane fraction. Moreover, the accumulation of nuclear symplekin promoted cell proliferation and dedifferentiation as well as β-catenin transactivation in vitro. Nuclear symplekin acts as a transcriptional co-activator for the expression of many cell cycle-related genes. Furthermore, extracellular signal-regulated kinase (ERK) phosphorylated symplekin at T1257 to facilitate its nuclear accumulation upon epidermal growth factor (EGF) stimulation. Meanwhile, reduction of total symplekin also induced certain epithelial-mesenchymal transition features in HT-29 cells. Taken together, our results confirm the coordinated roles of symplekin in cell junctions and gene transcription, which are related to its subcellular localization. The significance of nuclear symplekin in tumorigenesis is also highlighted, and ERK-dependent phosphorylation represents a mechanism for its subcellular sorting.

Abstract The role that serum uric acid (UA) plays in the pathophysiological development of erectile dysfunction (ED) is controversial. We aimed to screen the factors related with ED, and to examine the association between serum UA and ED. Our data were derived from a cross-sectional Survey on Prevalence in East China for Metabolic Diseases and Risk Factors study in 2014–2015. Questionnaire of International Index of Erectile Dysfunction-5 was used for assessment of ED. Data were collected in three general communities respectively. A total of 1365 men were enrolled with an overall mean age 55.5 ± 10.8 years (range: 20–83 years). The prevalence of ED was 62.4% (51.4% standardized) in the population. Males with ED were older, and more prone to have a higher follicle-stimulating hormone, luteinizing hormone, sex hormone-binding globulin, glycated hemoglobin, fasting plasma glucose levels and lower free androgen index (FAI), UA levels, and more likely to have diabetes and elevated blood pressure compared with those without ED. Age and UA were independent influencing factors for ED. Besides, UA was positively correlated with FAI after adjustment for age. In conclusion, our study demonstrated the protective role that UA might play in development of ED.

Abstract Few studies have investigated the association between serum uric acid (UA) and cadmium exposure. Our previous study revealed a significantly higher blood cadmium (CdB) level in the Chinese population compared to populations in other countries. To determine whether CdB in Chinese adults is associated with serum UA and hyperuricemia, 2996 participants from the cross-sectional SPECT-China study were recruited. CdB was measured by atomic absorption spectrometry. Hyperuricemia was defined as a serum UA concentration ≥416.4 μmol/L for men and ≥356.9 μmol/L for women. Regression analyses were used to analyze the association of CdB with serum UA and hyperuricemia. We found that the median CdB level was higher in men with hyperuricemia (2.40 μg/L) than in men without hyperuricemia (1.98 μg/L, P 60 mL/min per 1.73 m2. Further, the odds ratio of hyperuricemia increased with increasing CdB quartiles (P for trend

Abstract Lipid based nanocarriers are one of the most effective drug delivery systems that is evident from the recent COVID-19 mRNA vaccines. The main objective of this study was to evaluate toxicity of six lipid based formulations with three surface charges—anionic, neutral or cationic, to establish certified reference materials (CRMs) for liposomes and siRNA loaded lipid nanoparticles (LNP-siRNA). Cytotoxicity was assessed by a proliferation assay in adherent and non-adherent cell lines. High concentration of three LNP-siRNAs did not affect viability of suspension cells and LNP-siRNAs were non-toxic to adherent cells at conventionally used concentration. Systematic evaluation using multiple vials and repeated test runs of three liposomes and three LNP-siRNA formulations showed no toxicity in HL60 and A549 cells up to 128 and 16 µg/mL, respectively. Extended treatment and low concentration of LNPs did not affect the viability of suspension cells and adherent cells at 96 h. Interestingly, 80% of A549 and HL60 cells in 3D conditions were viable when treated with cationic LNP-siRNA for 48 h. Taken together, anionic, cationic and neutral lipid formulations were non-toxic to cells and may be explored further in order to develop them as drug carriers.