Search

Highlights Unique inter-skeleton conductive films are constructed in polymer foam. The resistance change of the foam can reach four orders of magnitude under compression. This foam exhibits strain-adaptive electromagnetic interference shielding performance, anti-interference pressure sensor with high sensitivity over a wide pressure range and compression-regulated Joule heating function.

Abstract Zika virus (ZIKV) infection may lead to severe neurological consequences, including seizures, and early infancy death. However, the involved mechanisms are still largely unknown. TRPC channels play an important role in regulating nervous system excitability and are implicated in seizure development. We investigated whether TRPCs might be involved in the pathogenesis of ZIKV infection. We found that ZIKV infection increases TRPC4 expression in host cells via the interaction between the ZIKV-NS3 protein and CaMKII, enhancing TRPC4-mediated calcium influx. Pharmacological inhibition of CaMKII decreased both pCREB and TRPC4 protein levels, whereas the suppression of either TRPC4 or CaMKII improved the survival rate of ZIKV-infected cells and reduced viral protein production, likely by impeding the replication phase of the viral life cycle. TRPC4 or CaMKII inhibitors also reduced seizures and increased the survival of ZIKV-infected neonatal mice and blocked the spread of ZIKV in brain organoids derived from human-induced pluripotent stem cells. These findings suggest that targeting CaMKII or TRPC4 may offer a promising approach for developing novel anti-ZIKV therapies, capable of preventing ZIKV-associated seizures and death.

The drivers of changes in gut microbiota under arsenic exposure and the mechanism by which microbiota affect arsenic metabolism are still unclear. Here, C57BL/6 mice were exposed to 0, 5, or 10 ppm NaAsO2 in drinking water for 6 months. The results showed that arsenic exposure induced liver injury and increased the abundance of folic acid (FA)/vitamin B12 (VB12)- and butyrate-synthesizing microbiota. Statistical analysis and in vitro cultures showed that microbiota were altered to meet the demand for FA/VB12 by arsenic metabolism and to resist the toxicity of unmetabolized arsenic. However, at higher arsenic levels, changes of these microbiota were inconsistent. A 3D molecular simulation showed that arsenic bound to methionine synthase (MTR), which was confirmed by SEC-UV-DAD (1 μM recombinant human MTR was purified with 0 or 2 μM NaAsO2 at room temperature for 1 h) and fluorescence-labeled arsenic co-localization (primary hepatocytes were exposed to 0, 0.5, or 1 μM ReAsH-EDT2 for 24 h) in non-cellular and cellular systems. Mechanistically, the arsenic-MTR interaction in the liver interferes with the utilization of FA/VB12, which increases arsenic retention and thus results in a substantial increase in the abundance of butyrate-synthesizing microbiota compared to FA/VB12-synthesizing microbiota. By exposing C57BL/6J mice to 0 or 10 ppm NaAsO2 with or without FA (6 mg/L) and VB12 (50 μg/L) supplementation in their drinking water for 6 months, we constructed an FA/VB12 intervention mouse model and found that FA/VB12 supplementation blocked the disturbance of gut microbiota, restored MTR levels, promoted arsenic metabolism, and alleviated liver injury. We demonstrate that the change of gut microbiota is a response to arsenic metabolism, a process influenced by the arsenic-MTR interaction. This study provides new insights for understanding the relationship between gut microbiota and arsenic metabolism and present therapeutic targets for arseniasis.

Abstract Hydrogen-isotope storage materials are essential for the controlled nuclear fusion. However, the currently used smelting-ZrCo alloy suffers from rapid degradation of performance due to severe disproportionation. Here, we reveal a defect-derived disproportionation mechanism and report a nano-single-crystal strategy to solve ZrCo’s problems. Single-crystal nano-ZrCo is synthesized by a wet-chemistry method and exhibits excellent comprehensive hydrogen-isotope storage performances, including ultrafast uptake/release kinetics, high anti-disproportionation ability, and stable cycling, far superior to conventional smelting-ZrCo. Especially, a further incorporation of Ti into nano-ZrCo can almost suppress the disproportionation reaction. Moreover, a mathematical relationship between dehydrogenation temperature and ZrCo particle size is established. Additionally, a microwave method capable of nondestructively detecting the hydrogen storage state of ZrCo is developed. The proposed disproportionation mechanism and anti-disproportionation strategy will be instructive for other materials with similar problems.

Abstract Background Although dietary intake is believed to be associated with constipation, there is currently a lack of research exploring the relationship between niacin intake and constipation. Therefore, the aim of this study is to investigate the association between niacin intake in adults and constipation using data from the National Health and Nutrition Examination Survey (NHANES). Methods This study included 5170 participants (aged ≥ 20 years) from the NHANES survey conducted between 2009 and 2010. Participants who reported experiencing constipation “always”, “most of the time”, or “sometimes” in the past 12 months were defined as constipation cases. The daily niacin intake was obtained from dietary recall and dietary supplement recalls of the patients. Weighted multivariate logistic regression analysis, restricted cubic spline regression, subgroup analysis, and interaction analysis were used to assess the correlation between niacin intake and constipation. Results After adjustment for covariates, the multivariate logistic regression model showed that low niacin intake was associated with a higher risk of constipation (Model 1: OR: 0.917, 95% CI 0.854–0.985, P = 0.023; Model 2: OR: 0.871, 95% CI 0.794–0.955, P = 0.01). After dividing niacin intake into four groups, a daily intake of 0–18 mg niacin was associated with a higher risk of constipation (Model 1: OR: 1.059, 95% CI 1.012–1.106, P = 0.019; Model 2: OR: 1.073, 95% CI 1.025–1.123, P = 0.013). The restricted cubic spline regression analysis also showed a non-linear relationship between niacin intake and the risk of constipation. Conclusion The findings of this study suggested that daily intake of 0–18 mg of niacin was associated with a higher risk of constipation compared to a daily intake of 18–27 mg of niacin.

Severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie Banda virus, is an emerging tick-borne Bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS). Currently, symptomatic treatment and antiviral therapy with ribavirin and favipiravir are used in clinical management. However, their therapeutical efficacy is hardly satisfactory in patients with high viral load. In this study, we explored the antiviral effects of selective estrogen receptor modulators (SERMs) on SFTSV infection and the antiviral mechanisms of a representative SERM, bazedoxifene acetate (BZA). Our data show that SERMs potently inhibited SFTSV-induced cytopathic effect (CPE), the proliferation of infectious viral particles, and viral RNA replication and that BZA effectively protected mice from lethal viral challenge. The mode of action analysis reveals that BZA exerts antiviral effects during the post-entry stage of SFTSV infection. The transcriptome analysis reveals that GRASLND and CYP1A1 were upregulated, while TMEM45B and TXNIP were downregulated. Our findings suggest that SERMs have the potential to be used in the treatment of SFTSV infection.

Background: Obesity, a chronic metabolic disorder, is related to cardiovascular diseases, diabetes, cancer, and reproductive disorders. The relationship between obesity and male infertility is now well recognized, but the mechanisms involved are unclear. We aimed to observe the effect of obesity on spermatogenesis and to investigate the role of histone ubiquitination and acetylation modifications in obesity-induced spermatogenesis disorders. Methods: Thirty male C57BL/6J mice were randomly divided into two groups. The control group was fed with a general maintenance diet (12% fat), while a high-fat diet (HFD) group was fed with 40% fat for 10 weeks; then, they were mated with normal females. The fertility of male mice was calculated, testicular and sperm morphology were observed, and the expression levels of key genes and the levels of histone acetylation and ubiquitination modification during spermatogenesis were detected. Results: The number of sperm was decreased, as well as the sperm motility, while the number of sperm with malformations was increased. In the testes, the mRNA and protein expression levels of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), chromosome region maintenance-1 protein (CRM1), high-mobility group B2 (HMGB2), phosphoglycerate kinase 2 (PGK2), and testicular angiotensin-converting enzyme (tACE) were decreased. Furthermore, obesity led to a decrease in ubiquitinated H2A (ubH2A) and reduced levels of histone H3 acetylation K18 (H3AcK18) and histone H4 acetylation K5, K8, K12, and K16 (H4tetraAck), which disrupted protamine 1 (Prm1) deposition in testis tissue. Conclusion: These results suggest that low levels of histone ubiquitination and acetylation are linked with obesity-induced disorders during spermatogenesis, contributing to a better understanding of obesity-induced damage to male reproduction.

Abstract Background Hepatocarcinogenesis is driven by necroinflammation or metabolic disorders, and the underlying mechanisms remain largely elusive. We previously found that retinoic acid-inducible gene-I (RIG-I), a sensor for recognizing RNA virus in innate immune cells, is mainly expressed by parenchymal hepatocytes in the liver. However, its roles in hepatocarcinogenesis are unknown, which is intensively investigated in this study. Methods DEN-induced necroinflammation-driven hepatocarcinogenesis and STAM NASH-hepatocarcinogenesis were carried out in hepatocyte-specific RIG-I knockout mice. The post-translational modification of RIG-I was determined by mass spectrometry, and specific antibodies against methylated lysine sites and the RIG-I lysine mutant mice were constructed to identify the functions of RIG-I methylation. Results We interestingly found that DEN-induced hepatocarcinogenesis was enhanced, while NASH-induced hepatocarcinogenesis was suppressed by hepatocyte-specific RIG-I deficiency. Further, IL-6 decreased RIG-I expression in HCC progenitor cells (HcPCs), which then viciously promoted IL-6 effector signaling and drove HcPCs to fully established HCC. RIG-I expression was increased by HFD, which then enhanced cholesterol synthesis and steatosis, and the in-turn NASH and NASH-induced hepatocarcinogenesis. Mechanistically, RIG-I was constitutively mono-methylated at K18 and K146, and demethylase JMJD4-mediated RIG-I demethylation suppressed IL-6-STAT3 signaling. The constitutive methylated RIG-I associated with AMPKα to inhibit HMGCR phosphorylation, thus promoting HMGCR enzymatic activity and cholesterol synthesis. Clinically, RIG-I was decreased in human hepatic precancerous dysplastic nodules while increased in NAFLD livers, which were in accordance with the data in mouse models. Conclusions Decreased RIG-I in HcPCs promotes necroinflammation-induced hepatocarcinogenesis, while increased constitutive methylated RIG-I enhances steatosis and NASH-induced hepatocarcinogenesis. JMJD4-demethylated RIG-I prevents both necroinflammation and NASH-induced hepatocarcinogenesis, which provides mechanistic insight and potential target for preventing HCC.

Electrochemically deposited sensors and DNA biosensors have been widely used in the food industry, and various other fields due to their high sensitivity, fast response, easy operation, no pollution, and low price. A rare earth electrochemically deposited gadolinium ferricyanide thin film modified glassy carbon electrode, and the investigation of electrocatalytic oxidation of guanine by GaHCF/GCE is reported. We deposited electrochemically a rare earth terbium ferricyanide thin film modified glassy carbon electrode. OH was investigated through various characteristics such as capacitance–voltage, Differential Pulse Voltammetric and many more by the comparison of catalytic oxidation signal of guanine with ·OH in Fenton reaction.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a superfamily of RNA-binding proteins consisting of more than 20 members. These proteins play a crucial role in various biological processes by regulating RNA splicing, transcription, and translation through their binding to RNA. In the context of muscle development and regeneration, hnRNPs are involved in a wide range of regulatory mechanisms, including alternative splicing, transcription regulation, miRNA regulation, and mRNA stability regulation. Recent studies have also suggested a potential association between hnRNPs and muscle-related diseases. In this report, we provide an overview of our current understanding of how hnRNPs regulate RNA metabolism and emphasize the significance of the key members of the hnRNP family in muscle development. Furthermore, we explore the relationship between the hnRNP family and muscle-related diseases.

At present, most stability control systems based on active steering are superposition control of steering Angle. For the steering system configuration commonly used in automatic driving vehicles, the active steering control system of steering angle superposition cannot be realized. In order to achieve man-machine collaborative driving, the co-driving intelligent vehicles usually realize automatic steering control based on the torque superposition, which solves the drawback that the driver of the Angle superposition cannot participate in the steering. In this paper, an active steering control method of superposition of steering torque based on Receding horizon control is proposed for man-machine collaborative driving of co-drive intelligent vehicles. This control method combines steering system with vehicle dynamics system, and takes steering motor torque as the sole control input, which ensures that the driver has the ultimate control right and makes the control of the system more stable. In order to solve the system uncertainties caused by model mismatch and external disturbances, the optimal control rate in predictive time domain can be calculated according to real-time vehicle state parameters by receding horizon control. In the design of the controller, the yaw rate deviation is the input of the controller, and then the calculated superposition torque is input into the vehicle model in real time, and the steering wheel angle is observed as a state variable. The control strategy can effectively compensate for the uncertainty of the system such as model mismatch and external disturbance, and enhance the robustness of the system.

Improving the prediction accuracies of economically important traits in genomic selection (GS) is a main objective for researchers and breeders in the livestock industry. This study aims at utilizing potentially functional SNPs and QTLs identified with various genome-wide association study (GWAS) models in GS of pig growth traits. We used three well-established GWAS methods, including the mixed linear model, Bayesian model and meta-analysis, as well as 60K SNP-chip and whole genome sequence (WGS) data from 1734 Yorkshire and 1123 Landrace pigs to detect SNPs related to four growth traits: average daily gain, backfat thickness, body weight and birth weight. A total of 1485 significant loci and 24 candidate genes which are involved in skeletal muscle development, fatty deposition, lipid metabolism and insulin resistance were identified. Compared with using all SNP-chip data, GS with the pre-selected functional SNPs in the standard genomic best linear unbiased prediction (GBLUP), and a two-kernel based GBLUP model yielded average gains in accuracy by 4 to 46% (from 0.19 ± 0.07 to 0.56 ± 0.07) and 5 to 27% (from 0.16 ± 0.06 to 0.57 ± 0.05) for the four traits, respectively, suggesting that the prioritization of preselected functional markers in GS models had the potential to improve prediction accuracies for certain traits in livestock breeding.

Chemically exfoliated nanosheets have been extensively employed as functional nanofillers for the fabrication of polymer nanocomposites due to their remarkable electrical, magnetic and optical properties. However, achieving a good dispersion of charged nanosheets in polymer matrix, which will determine the performance of polymer nanocomposites, remains a challenge. Herein, we investigated the dispersion and aggregation behavior of negatively charged Ca2Nb3O10 (CNO) perovskite nanosheets in negatively charged sodium alginate (SA) aqueous dispersion using dynamic light scattering (DLS). When CNO nanosheets meet with SA, aggregation and coagulation inevitably occurred owing to the absorption of SA on nanosheets. By controlling the electrostatic attraction between positively charged poly(ethylene imine) (PEI) and negatively charged SA, the charge density and hydrodynamic size of SA can be tuned to enable the good dispersion of CNO nanosheets in SA. This result may provide a new strategy to achieve the good dispersion of charged nanosheets in charged polymers for the rational design of multifunctional nanocomposites.

Pleckstrin-2 (PLEK2) is a crucial mediator of cytoskeletal reorganization. However, the potential roles of PLEK2 in gastric cancer are still unknown. PLEK2 expression in gastric cancer was examined by western blotting and real-time PCR. Survival analysis was utilized to test the clinical impacts of the levels of PLEK2 in gastric cancer patients. In vitro and in vivo studies were used to estimate the potential roles played by PLEK2 in modulating gastric cancer proliferation, self-renewal, and tumourigenicity. Bioinformatics approaches were used to monitor the effect of PLEK2 on epithelial-mesenchymal transition (EMT) signalling pathways. PLEK2 expression was significantly upregulated in gastric cancer as compared with nontumour samples. Kaplan-Meier plotter analysis revealed that gastric cancer patients with higher PLEK2 levels had substantially poorer overall survival compared with gastric cancer patients with lower PLEK2 levels. The upregulation or downregulation of PLEK2 in gastric cancer cell lines effectively enhanced or inhibited cell proliferation and proinvasive behaviour, respectively. Additionally, we also found that PLEK2 enhanced EMT through downregulating E-cadherin expression and upregulating Vimentin expression. Our findings demonstrated that PLEK2 plays a potential role in gastric cancer and may be a novel therapeutic target for gastric cancer.

The formation of paraspeckle, a stress-induced nuclear body, increases in response to viral infection or proinflammatory stimuli. Paraspeckle consists of lncRNA (nuclear paraspeckle assembly transcript 1, NEAT1) and protein components including NONO, SFPQ, PSPC1, etc., which are shown to be involved in viral infection and cancer. Both NEAT1 and NONO expression increase in human hepatocellular carcinoma (HCC) samples according to TCGA data. However, the role of paraspeckle in HCC progression needs further identification. IL-6 signaling is well known to contribute to HCC progression. Here we reported that IL-6 signaling increased paraspeckle formation in HCC cells. Destruction of paraspeckle formation by silencing the paraspeckle essential components NEAT1_2 or NONO could suppress IL-6-induced STAT3 phosphorylation in HCC cells, and consequently repressed IL-6-promoted in vitro HCC cell invasion, cell cycle progression and survival. Mechanistically, paraspeckle promotes IL-6-induced STAT3 phosphorylation by binding and trapping peroxiredoxin-5 (PRDX5) mRNA in nucleus, decreasing protein level of PRDX5 which can directly interact with STAT3 and inhibit STAT3 phosphorylation. Besides, glutathione S-transferase P (GSTP1) protein, which inhibits DNA damage and apoptosis through its detoxification and anti-oxidation function, was also trapped within paraspeckles under IL-6 stimulation. Paraspeckle-trapping of both PRDX5 mRNA and GSTP1 protein contributes to IL-6-increased DNA damage in HCC cells. Our results demonstrate that paraspeckle can nuclear entrap the inhibitors of IL-6/STAT3 signaling as well as DNA damage, and then strengthen the promoting effect on HCC progression by IL-6. Therefore, paraspeckle contributes to the inflammation-related HCC progression and might be a potential therapeutic target for HCC.

In recent years, entity-based ranking models have led to exciting breakthroughs in the research of information retrieval. Compared with traditional retrieval models, entity-based representation enables a better understanding of queries and documents. However, the existing entity-based models neglect the importance of entities in a document. This paper attempts to explore the effects of the importance of entities in a document. Specifically, the dataset analysis is conducted which verifies the correlation between the importance of entities in a document and document ranking. Then, this paper enhances two entity-based models—toy model and Explicit Semantic Ranking model (ESR)—by considering the importance of entities. In contrast to the existing models, the enhanced models assign the weights of entities according to their importance. Experimental results show that the enhanced toy model and ESR can outperform the two baselines by as much as 4.57% and 2.74% on NDCG@20 respectively, and further experiments reveal that the strength of the enhanced models is more evident on long queries and the queries where ESR fails, confirming the effectiveness of taking the importance of entities into account.

The (1 + 2)-dimensional nonlinear Schrödinger equation with dual-power law nonlinearity is studied using the factorization technique, bifurcation theory of dynamical system, and phase portraits analysis. From a dynamic point of view, the existence of smooth solitary wave, and kink and antikink waves is proved and all possible explicit parametric representations of these waves are presented.

Abstract Background Conflicting results comparing bivalirudin versus heparin anticoagulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), in part due to the confounding effect of glycoprotein IIb/IIIa inhibitors (GPI). The aim of the study was to compare the safety and effectiveness of bivalirudin plus a post-PCI high-dose infusion vs heparin with or without bail-out GPI use. Methods We conducted a pre-specified subgroup analysis from the BRIGHT-4 trial that randomized 6016 STEMI patients who underwent primary PCI to receive either bivalirudin plus a post-PCI high-dose infusion for 2–4 h or heparin monotherapy. GPI use was only reserved as bail-out therapy for procedural thrombotic complications. The primary outcome was a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3–5 bleeding at 30 days. Results A total of 5250 (87.4%) patients received treatment without GPI while 758 (12.6%) received bail-out GPI. Bail-out GPI use was associated with an increased risk of the primary outcome compared to non-GPI use (5.28% vs. 3.41%; adjusted hazard ratio (aHR), 1.62; 95% confidence interval (CI), 1.13–2.33; P = 0.009) and all-cause death (5.01% vs. 3.12%; aHR, 1.74; 95% CI, 1.20–2.52; P = 0.004) but not in the risk of BARC types 3–5 bleeding (0.53% vs. 0.48%; aHR, 0.90; 95% CI, 0.31–2.66; P = 0.85). Among patients without GPI use, bivalirudin was associated with lower rates of the primary outcome (2.63% vs. 4.21%; aHR, 0.55; 95% CI, 0.39–0.77; P = 0.0005), all-cause death (2.52% vs. 3.74%; aHR, 0.58; 95% CI, 0.41–0.83; P = 0.003), and BARC types 3–5 bleeding (0.15% vs. 0.81%; aHR, 0.19; 95% CI, 0.06–0.57; P = 0.003) compared with heparin. However, among patients requiring bail-out GPI, there were no significant differences observed in the rates of the primary outcome (5.76% vs. 4.87%; aHR, 0.77; 95% CI, 0.36–1.66; P = 0.50; P interaction = 0.07) or its individual components between bivalirudin and heparin groups. Conclusions Bivalirudin plus a post-PCI high-dose infusion was associated with significantly reduced 30-day composite rate of all-cause death or BARC types 3–5 bleeding compared with heparin monotherapy in STEMI patients undergoing primary PCI without GPI use. However, these benefits might be less pronounced in patients requiring bail-out GPI due to thrombotic complications during primary PCI. Trial registration ClinicalTrials.gov NCT03822975.