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Abstract The difficulty of adjusting the weighting coefficients of the cost function in traditional model predictive torque control is addressed by proposing a fixed weighting coefficient three‐vector model predictive torque control (FWC‐MPTC) strategy. The strategy applies three voltage vectors in a control period. The first voltage vector is selected by a fixed coefficient cost function, the second and third voltage vectors are determined by a cost function that includes only torque and flux, and the third voltage vector is no longer just a traditional zero vector. In addition, to solve the problem of poor disturbance immunity of the speed loop PI controller, an active disturbance rejection controller (ADRC) is introduced in the speed loop, and the error non‐linear function in the controller is rewritten into a smoother new function. The proposed control strategy reduces the torque and speed fluctuation of the traditional three‐vector model predictive control (TTV‐MPTC), improves the robustness of the system, avoids the difficulty of adjusting the weight coefficient in the traditional cost function, and reduces the computational complexity of the cost function.

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.

Toxic Epidermal Necrolysis (TEN) is a severe skin-mucosal reaction induced by medications, commonly characterized by blister formation and widespread epidermal detachment. Typical causative agents include allopurinol, antibiotics, anticonvulsants, and non-steroidal anti-inflammatory drugs (NSAIDs), with trimethoprim/sulfamethoxazole and penicillin being the most frequently implicated among antibiotics. However, lincosamide antibiotics as the cause of aggravation are rarely reported in clinical settings. This case report presents a patient with TEN induced by quinolone antibiotics, who experienced rapid progression of the condition after combining with lincomycin antibiotics. Clinical remission was achieved through a combination of corticosteroids, intravenous immunoglobulin, and plasma exchange therapy. This report aims to enhance clinicians’ understanding of TEN by providing a detailed case presentation and discussion.

Carbon capture and its storage is widely recognized as one of the primary approaches for reducing anthropogenic carbon emissions. The role of geophysical investigation is then for the selection of a suitable site for the geological storage of CO2 and the monitoring of the injection and storage process. The monitoring of the dynamic process can both detect leakage and minimize leakage potentials. To achieve this goal, this paper suggested the use of transient electromagnetic 3D finite-difference method to help realize the geospatial quantification of in-situ CO2. First, the horizontal model and the deep saline aquifer inclined were developed to analyze the low resistivity response which is the characteristic of typical aquifers. Second, the geoelectrical modeling which demonstrates the changes at the time of the CO2 injection, can be used to examine the temporal variations in subsurface resistivity. Thus, the impact to the volumetric changes due to the CO2 injection can be quantified. The significance of the results of this study confirmed the potential of the development of efficient dynamic monitoring and boundary delineation strategies for CO2 geological storage. Finally, a geoelectrical model for leakage has been established to investigate the likely changes in the resistivity of the subsurface strata because of CO2 leakage, which is reflected in the transient electromagnetic response patterns along with the leakage paths. This contributes to the monitoring of CO2 leakage in real time as well as detecting the location of leakage. This paper provided the theorical support of the transient electromagnetic method which has the potential to capture the dynamic diffusion process of CO2 storage in a deep saline aquifer. Furthermore, it could be used to an efficient monitor of CO2 leakage and identify the leakage paths.

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.

Defect detection and classification in super-high reflector mirrors and their substrates are crucial for manufacturing laser gyroscope systems. This paper presents a prototype designed to meet the requirements for the reflection and transmission of laser gyroscope mirror substrates. The prototype featured two measurement channels (bright field and dark field) and could detect defects on patterned and unpatterned surfaces. Key components were simulated using Ansys software, (Ansys Workbench 2022 R1)which showed a maximum static deformation of 4.65 μm, a resonant frequency of at least around 230 Hz, and a maximum stress of 9.86 MPa under transportation conditions (GJB150.16A-2009). These results confirm the prototype’s stability for optical performance testing and structural design. The experimental testing on laser gyroscope reflector substrates and USAF 1951 plates demonstrated that the prototype effectively detected defects on reflection and transmission surfaces, with a detection resolution that exceeded 170 nm, which met the design requirements.

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.

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.

Abstract Background The combination of anti‐PD‐1 antibody serplulimab and chemotherapy is considered standard first‐line therapy for advanced esophageal squamous cell carcinoma (ESCC), but few later‐line treatments are available. Here we evaluated the therapeutic efficacy of the recombinant, humanized anti‐EGFR antibody HLX07 when used alone or together with serplulimab and chemotherapy against advanced ESCC. Methods This open‐label, non‐randomized, two‐cohort, phase 2 trial involved patients 18‐75 years old with histologically or cytologically confirmed locally advanced, unresectable, or metastatic ESCC, and an Eastern Cooperative Oncology Group performance status of 0‐1. Patients who had failed first‐line immuno‐chemotherapy or at least two lines of other systemic therapy received HLX07 monotherapy intravenously at a dose of 1,000 mg once every 2 weeks (Q2W). Patients with no prior systemic therapy received HLX07 (1,000 mg, day 1) and serplulimab (200 mg, day 1) intravenously Q2W for up to 2 years, concurrently with cisplatin (50 mg/m2, day 1) for up to 8 cycles and 5‐fluorouracil (1,200 mg/m2, days 1‐2) for up to 12 cycles intravenously Q2W. The primary endpoints were progression‐free survival (PFS) and objective response rate (ORR). Results Overall, 50 patients were enrolled. In the HLX07 monotherapy group, ORR was 15.0% (3/20), and the median PFS was 1.5 months (95% confidence interval [CI], 1.3 to 3.7). The median duration of response was not reached, and the rate of patients showing an objective response lasting at least 6 months was 66.7% (95% CI, 5.4 to 94.5). Two (10.0%, 2/20) patients experienced grade 3‐4 treatment‐related adverse events (TRAEs), including hypomagnesemia, hypocalcemia, and fatigue. No patient experienced grade 5 TRAEs. In the HLX07 combination group, the ORR was 60.0% (18/30), and the median PFS was 7.8 months (95% CI, 3.3 to 9.1). Fourteen (46.7%, 14/30) patients experienced grade 3‐4 TRAEs, and one (3.3%, 1/30) patient died due to serplulimab‐related pneumonitis. Conclusions HLX07 monotherapy and its combination with serplulimab and chemotherapy showed manageable toxicity and promising antitumor activity in patients with recurrent or metastatic ESCC. Randomized controlled trials are warranted to further establish the safety and efficacy of HLX07 against ESCC. Trial registration This trial was registered at Clinicaltrials.gov (NCT05221658).

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.