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Abstract Background Aberrant alternative splicing (AS) events, triggered by the alterations in serine/arginine splicing factor 1 (SRSF1), a member of the SR protein family, have been implicated in various pathological processes. However, the function and mechanism of SRSF1 in cardiovascular diseases remain unclear. Results In this study, we found that the expression of SRSF1 was significantly down-regulated in the hearts of mice with acute myocardial infarction (AMI) and H9C2 cells exposed to H2O2. Moreover, in vivo experiments utilizing adeno-associated virus serotype 9-mediated SRSF1 overexpression improved cardiac function and reduced infarct size in AMI mice. Mechanistically, we employed RNA-seq assay to identify AS aberrations associated with altered SRSF1 level in cardiomyocytes, and found that SRSF1 regulates the splice switching of Bcl2L12. Further study showed that silencing SRSF1 inhibits the inclusion of exon7 in Bcl2L12. Importantly, the truncated Bcl2L12 lacked the necessary structural elements and failed to interact with p53, thus compromising its ability to suppress apoptosis. Conclusions Our study unraveled the role of SRSF1 as a splicing factor involved in the regulation of Bcl2L12 splice switching, thereby exerting an anti-apoptotic effect through the p53 pathway, which provides new insights into potential approaches targeting cardiomyocyte apoptosis in cardiovascular diseases.

Abstract Extracellular vesicles (EVs), especially those derived from stem cells, have emerged as a novel treatment for promoting wound healing in regenerative medicine. However, the clinical application of mammalian cells-derived EVs is hindered by their high cost and low yields. Inspired by the ability of EVs to mediate interkingdom communication, we explored the therapeutic potential of EVs released by the probiotic strain Lactobacillus rhamnosus GG (LGG) in skin wound healing and elucidated the underlying mechanism involved. Using full-thickness skin wound-healing mouse models, we found that LGG-EVs accelerated wound healing procedures, including increased re-epithelialization and promoted angiogenesis. Using in vitro experiments, we further demonstrated that LGG-EVs boosted the proliferation and migration capacities of both epithelial and endothelial cells, as well as promoted endothelial tube formation. miRNA profiling analysis revealed that miR-21-5p was highly enriched in LGG-EVs and LGG-EV treatment significantly increased miR-21-5p level in recipient cells. Mechanically, LGG-EVs induced regulatory effects via miR-21-5p mediated metabolic signaling rewiring. Our results suggest that EVs derived from LGG could serve as a promising candidate for accelerating wound healing and possibly for treating chronic and impaired healing conditions. Graphical abstract

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by the overproliferation of synovial fibroblast‐like synoviocytes (FLSs) in the lining, leading to chronic inflammation and progressive joint damage. RA pathogenesis involves lymphocyte infiltration, increased synovial cell proliferation, and impaired cell death. This study investigated the effects of rapamycin on RA‐FLSs and explored the underlying molecular mechanisms. Methods The optimal drug concentration and time for rapamycin administration were determined using a cell counting kit‐8 assay. The concentration of rapamycin varied from 1 to 25 nmol/L. The mRNA expression levels of protein kinase B (AKT), mammalian target of rapamycin (mTOR), B cell lymphoma 2 (Bcl‐2), and Bcl‐2‐associated X protein (Bax) were quantified by real‐time polymerase chain reaction. Protein expression (p‐AKT, AKT, p‐mTOR, mTOR, pS6 kinase [S6K], S6K, p‐4E‐binding protein 1 [4EBP1], 4EBP1, Bcl‐2, Bax, caspase 3, caspase 9, cyclin‐dependent kinase 2 [CDK2], and CD1) were detected by Western blotting analysis. Results Rapamycin suppresses RA‐FLS proliferation and induces apoptosis in a dose‐dependent manner. Rapamycin significantly elevated the protein expression of Bax (p

Abstract Background The risk assessment for survival in heart failure (HF) remains one of the key focuses of research. This study aims to develop a simple and feasible nomogram model for survival in HF based on the Heart Failure-A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) to support clinical decision-making. Methods The HF patients were extracted from the HF-ACTION database and randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Multivariate Cox regression was used to identify and integrate significant prognostic factors to form a nomogram, which was displayed in the form of a static nomogram. Bootstrap resampling (resampling = 1000) and cross-validation was used to internally validate the model. The prognostic performance of the model was measured by the concordance index (C-index), calibration curve, and the decision curve analysis. Results There were 1394 patients with HF in the overall analysis. Seven prognostic factors, which included age, body mass index (BMI), sex, diastolic blood pressure (DBP), exercise duration, peak exercise oxygen consumption (peak VO2), and loop diuretic, were identified and applied to the nomogram construction based on the training cohort. The C-index of this model in the training cohort was 0.715 (95% confidence interval (CI): 0.700, 0.766) and 0.662 (95% CI: 0.646, 0.752) in the validation cohort. The area under the ROC curve (AUC) value of 365- and 730-day survival is (0.731, 0.734) and (0.640, 0.693) respectively in the training cohort and validation cohort. The calibration curve showed good consistency between nomogram-predicted survival and actual observed survival. The decision curve analysis (DCA) revealed net benefit is higher than the reference line in a narrow range of cutoff probabilities and the result of cross-validation indicates that the model performance is relatively robust. Conclusions This study created a nomogram prognostic model for survival in HF based on a large American population, which can provide additional decision information for the risk prediction of HF.

BackgroundThere are gender differences in hypertension and the effect of gender on the relationship between systemic immune-inflammation index (SII) and mortality in hypertensive patients is unclear.MethodsHypertensive patients (n=7444) from ten cycles of the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018 were enrolled in this study. The maximally selected rank statistics method was employed to identify the optimal cut-off value for the SII. Survey-weighted Cox regression analysis was utilized to explore the links between SII and all-cause and cardiovascular mortality. Kaplan-Meier method and time-dependent receiver operating characteristic curve analysis was conducted to assess the predictive accuracy of SII for mortality.ResultsWhether SII was considered as a numerical variable or as a binary variable (higher- and lower-SII groups), higher SII levels were associated with a higher risk of all-cause and cardiovascular mortality in female hypertensive patients (all P < 0.001), but no such association was observed in the males. The area under the curve of the SII was 0.602, 0.595, and 0.569 for 3-, 5-, and 10-year all-cause mortality, respectively, in females, but was 0.572, 0.548, and 0.554 in males. High SII levels interacted with the poverty income ratio and physical activity to affect mortality in the male population (P for interaction < 0.05), and there was an interaction between race and SII in the female cardiovascular mortality rate (P for interaction < 0.05).ConclusionHigher levels of SII may be closely related to the high risk of all-cause and cardiovascular mortality in hypertensive patients, and the results showed that this relationship is more significant and stable in the female group. High SII interacts with PIR, physical activity, and race to affect the mortality rate in different gender populations.

Alkylphenols are widely applied in the field of industry and agriculture, but their endocrine disrupting properties harm to human health. Moreover, alkylphenols often exhibit the low content in complex samples. Thus, we proposed magnetic covalent organic framework composites (Fe3O4@TatTpa) for efficient magnetic solid phase extraction (MSPE) of alkylphenols via hydrogen bonding, π-π and hydrophobic interactions. In combination with HPLC detection, good linearity (0.006–10 µg mL−1) with R2 (≥0.997) and low limit of detections (1.8–6 × 10−3 µg mL−1) were realized for alkylphenols. The proposed method was successfully employed to determine alkylphenols in soft drink, black oolong tea, and watermelon samples with satisfactory recoveries (86.1–118.5 %) and relative standard deviations (6.3–14.8 %).

Background: Observational evidence suggests that type 1 diabetes mellitus (T1DM) is associated with the risk of osteoporosis (OP). Nevertheless, it is not apparent whether these correlations indicate a causal relationship. To elucidate the causal relationship, a two-sample Mendelian randomization (MR) analysis was performed. Methods: T1DM data was obtained from the large genome-wide association study (GWAS), in which 6683 cases and 12,173 controls from 12 European cohorts were involved. Bone mineral density (BMD) samples at four sites were extracted from the GEnetic Factors for OSteoporosis (GEFOS) consortium, including forearm (FA) (n = 8,143), femoral neck (FN) (n = 32,735), lumbar spine (LS) (n = 28,498), and heel (eBMD) (n = 426,824). The former three samples were from mixed populations and the last one was from European. Inverse variance weighting, MR-Egger, and weighted median tests were used to test the causal relationship between T1DM and OP. A series of sensitivity analyses were then conducted to verify the robustness of the results. Results: Twenty-three independent SNPs were associated with FN-BMD and LS-BMD, twenty-seven were associated with FA-BMD, and thirty-one were associated with eBMD. Inverse variance-weighted estimates indicated a causal effect of T1DM on FN-BMD (odds ratio (OR) =1.033, 95 % confidence interval (CI): 1.012–1.054, p = 0.002) and LS-BMD (OR = 1.032, 95 % CI: 1.005–1.060, p = 0.022) on OP risk. Other MR methods, including weighted median and MR-Egger, calculated consistent trends. While no significant causation was found between T1DM and the other sites (FA-BMD: OR = 1.008, 95 % CI: 0.975–1.043, p = 0.632; eBMD: OR = 0.993, 95 % CI: 0.985–1.001, p = 0.106). No significant heterogeneity (except for eBMD) or horizontal pleiotropy was found for instrumental variables, suggesting these results were reliable and robust. Conclusions: This study shows a causal relationship between T1DM and the risk of some sites of OP (FN-BMD, LS-BMD), allowing for continued research to discover the clinical and experimental mechanisms of T1DM and OP. It also contributes to the recommendation if patients with T1DM need targeted care to promote bone health and timely prevention of osteoporosis.

A novel p–n heterojunctions composite of BiBaO3 and Ag3PO4 were synthesized to significantly enhance the degradation efficiency of antibiotic wastewater. Through compositional analysis, micron-sized BiBaO3 particles were combined with nano-sized Ag3PO4 particles, resulting in a composite (Ag/0.75Bi) with excellent visible light absorption properties. Moreover, the photocatalytic efficiency was evaluated for Tetracycline and Oxytetracycline degradation, demonstrating remarkable degradation efficiencies. Under visible light irradiation, pollutants were degraded almost completely within 40 min, while the composite photocatalysts exhibited acceptable stability. The photocatalyst mechanism was investigated by conducting photoelectric effect, free radical capturing, and detection experiments. The p-type BiBaO3 and n-type Ag3PO4 compound facilitated the transfer of photogenerated electrons and holes, reducing their recombination probability and improving photocatalytic efficiencies. Furthermore, hydroxyl and superoxide radicals played a crucial role in the photodegradation of pollutants. Overall, this study provides novel insights into the development of composite catalyst for the photocatalytic degradation of antibiotic wastewater.

Abstract Introduction Currently, the cause of psoriatic arthritis (PsA) is unknown, and the effectiveness of current drug treatments is unsatisfactory. In March 2019, the US Food and Drug Administration (FDA) approved risankizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, for the treatment of PsA in adults. This study aimed to conduct a meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the effectiveness and safety of risankizumab in moderate-to-severe PsA. Methods We conducted a thorough search of relevant databases from the establishment of the databases to October 1, 2023. We conducted a meta-analysis using Stata 12.0 and utilized I 2 and Egger tests to assess heterogeneity and publication bias among the studies. Bias assessment was performed using the risk bias map and bias risk summary diagram generated by Revman5.4 software. The review protocols were registered on PROSPERO (CRD42023451894) and adhered to the preferred reporting item of system evaluation (PRISMA) guideline. Results Six randomized controlled trials (RCTs) involving 5038 patients with PsA treated with either risankizumab or placebo were included in the analysis. At 24 weeks, the risankizumab group demonstrated a significantly higher American College of Rheumatology-20 (ACR20) response rate compared to the placebo group (RR 1.760, 95% CI 1.568–1.977, P

The electrochemical hydrogen evolution reaction (HER) stands as a burgeoning clean energy prospect. This work synthesized composite materials (CMOxCNT), exhibiting exceptional electrocatalytic prowess, emerged from the fusion of cobalt molybdate (CMO) and carbon nanotubes (CNT). The outcomes of characterization established the CMO as a hydrated cobalt molybdate mineral, the theoretical molecular formula CoMoO4·nH2O. The CMO particles demonstrated a distinctive rod-shaped morphology. Notably, under the optimal mass ratio (CMO/CNT=7/3), carbon nanotubes exhibited partial coverage of the CMO particle surface. Electrochemical hydrogen evolution experiments decisively illuminated the catalytic potency of the CMO-CNT composites, which effectively improved the HER efficiency. The CMO3CNT, distinguished by elevated electrochemically active surface area, yielded a lower HER overpotential of 171.5 mV (at 10 mA·cm−2) and Tafel slope of 69.9 mV dec−1. Importantly, the material demonstrated commendable catalytic stability across a 30-hour span of i-t tests and 3000 CV cycles. Density Functional Theory (DFT) analyses unveiled at the adept electron transfer capabilities in CNT and favorable catalytic ability exhibited in CMO contributed substantively to the composite's overall efficacy. The remarkable catalytic proficiency of CMO stemmed from the synergistic interplay between cobalt and molybdenum atoms. The amalgamation of both inherent advantages engendered the composite's pronounced electrocatalytic performance.

Abstract Background Epidemiological studies have shown a close association between osteoarthritis (OA) and cardiovascular disease (CVD), but reliable evidence needs to be provided. We performed a two‐sample Mendelian randomization (MR) study to examine the potential causal effect between OA and CVD. Methods Exposures were self‐reported OA, knee osteoarthritis (KOA), and hip osteoarthritis (HOA). The outcomes were 12 CVDs, including heart failure, atrial fibrillation, coronary artery disease, pulmonary embolism, stroke and its subtypes, myocardial infarction, coronary heart disease, and primary hypertension. All outcomes were obtained from published genome‐wide association studies. The inverse‐variance weighted method was used as the primary MR analysis. Heterogeneity tests and sensitivity analyses were conducted to validate the accuracy of the MR results. Results Self‐reported OA increased the incidence of small vessel stroke (odds ratio [OR] = 1.25, 95% confidence interval [CI]: 1.02–1.52, p = 0.03) and primary hypertension (1.01 [1.00–1.02], p

BackgroundImmunotherapy targeting factors related to immune imbalance has been widely employed for RA treatment. This study aimed to evaluate the efficacy and safety of low-dose interleukin (IL)-2 combined with tocilizumab (TCZ), a biologics targeting IL-6, in RA patients.MethodsFifty adults with active RA who met the criteria with complete clinical data were recruited, and divided into three groups: control group (n=15), IL-2 group (n=26), and IL-2+TCZ group (n=9). In addition to basic treatment, participants in the IL-2 group received IL-2 (0.5 MIU/day), while participants in the IL-2+TCZ group received IL-2 (0.5 MIU/day) along with one dose of TCZ (8 mg/kg, maximum dose: 800 mg). All subjects underwent condition assessment, laboratory indicators and safety indicators detection, and records before treatment and one week after treatment.ResultsCompared with the baseline, all three groups showed significant improvement in disease conditions, as evidenced by significantly reduced disease activity indicators. The low-dose IL-2 and combination treatment groups demonstrated a violent proliferation of Tregs, while the absolute number of Th1, Th2, and Th17 cells in the latter group showed a decreasing trend. The decrease in the Th17/Treg ratio was more pronounced in the IL-2+TCZ groups. No significant adverse reactions were observed in any of the patients.ConclusionExogenous low doses of IL-2 combined TCZ were found to be safe and effective in reducing effector T cells and appropriately increasing Treg levels in RA patients with high effector T cell levels. This approach helps regulate immune homeostasis and contributes to the prevention of disease deterioration.Clinical trial registrationhttps://www.chictr.org.cn/showprojEN.html?proj=13909, identifier ChiCTR-INR-16009546.

ABSTRACTSeed metabolites are the combination of essential compounds required by an organism across various potential environmental conditions. The seed metabolites screening framework based on the network topology approach can capture important biological information of species. This study aims to identify comprehensively the relationship between seed metabolites and pathogenic bacteria. A large-scale data set was compiled, describing the seed metabolite sets and metabolite sets of 124,192 pathogenic strains from 34 genera, by constructing genome-scale metabolic models. The enrichment analysis method was used to screen the specific seed metabolites of each species/genus of pathogenic bacteria. The metabolites of pathogenic microorganisms database (MPMdb) (http://qyzhanglab.hzau.edu.cn/MPMdb/) was established for browsing, searching, predicting, or downloading metabolites and seed metabolites of pathogenic microorganisms. Based on the MPMdb, taxonomic and phylogenetic analyses of pathogenic bacteria were performed according to the function of seed metabolites and metabolites. The results showed that the seed metabolites could be used as a feature for microorganism chemotaxonomy, and they could mirror the phylogeny of pathogenic bacteria. In addition, our screened specific seed metabolites of pathogenic bacteria can be used not only for further tapping the nutritional resources and identifying auxotrophies of pathogenic bacteria but also for designing targeted bactericidal compounds by combining with existing antimicrobial agents.IMPORTANCEMetabolites serve as key communication links between pathogenic microorganisms and hosts, with seed metabolites being crucial for microbial growth, reproduction, external communication, and host infection. However, the large-scale screening of metabolites and the identification of seed metabolites have always been the main technical bottleneck due to the low throughput and costly analysis. Genome-scale metabolic models have become a recognized research paradigm to investigate the metabolic characteristics of species. The developed metabolites of pathogenic microorganisms database in this study is committed to systematically predicting and identifying the metabolites and seed metabolites of pathogenic microorganisms, which could provide a powerful resource platform for pathogenic bacteria research.

Reperfusion stands as a pivotal intervention for ischemic heart disease. However, the restoration of blood flow to ischemic tissue always lead to further damage, which is known as myocardial ischemia/reperfusion injury (MIRI). Ramelteon is an orally administered drug used to improve sleep quality, which is famous for its high bioadaptability and absence of notable addictive characteristics. However, the specific mechanism by which it improves MIRI is still unclear. Sirtuin-3 (Sirt3), primarily located in mitochondria, is crucial in mitigating many cardiac diseases, including MIRI. Based on the structure of Sirt3, we simulated molecular docking and identified several potential amino acid binding sites between it and ramelteon. Therefore, we propose a hypothesis that ramelteon may exert cardioprotective effects by activating the Sirt3 signaling pathway. Our results showed that the activation levels and expression level of Sirt3 were significantly decreased in MIRI tissue and H2O2 stimulated H9C2 cells, while ramelteon treatment upregulated Sirt3 activity and expression. After treat with 3-TYP, a classic Sirt3 activity inhibitor, we constructed myocardial ischemia/reperfusion surgery in vivo and induced H9C2 cells with H2O2 in vitro. The results showed that the myocardial protection and anti-apoptotic effects of ramelteon were antagonized by 3-TYP, indicating that the activation of Sirt3 is a key mechanism for ramelteon to exert myocardial protection. In summary, our results confirm a novel mechanism by which ramelteon improves MIRI by activating Sirt3 signaling pathway, providing strong evidence for the treatment of MIRI with ramelteon.

Abstract Rheumatoid arthritis (RA) is an autoimmune disease characterized by the accumulation of leukocytes and inflammatory mediators within the synovial tissue. Leukocyte counts are proposed to play a role in the pathogenesis of RA. However, the causality remains unclear. To investigate the causal relationship between various leukocytes and RA by implementing two-sample univariable Mendelian Randomization (MR) and multivariable MR. MR analysis was performed using respective genome-wide association study (GWAS) summary statistics for the exposure traits (eosinophil counts, neutrophil counts, lymphocyte counts, monocyte counts, basophil counts, and white blood cell counts) and outcome trait (RA). Summary statistics for leukocytes were extracted from the Blood Cell Consortium meta-analysis and INTERVAL studies. Public GWAS information for RA included 14,361 cases and 43,923 controls. Inverse variance weighted, weighted median, MR-Egger regression, MR pleiotropy residual sum and outlier, and multivariable MR analyses were performed in MR analysis. Univariable MR found elevated eosinophil counts (OR 1.580, 95% CI 1.389–2.681, p = 1.30 × 10–7) significantly increased the risk of RA. Multivariable MR further confirmed that eosinophil counts were a risk factor for RA. Increased eosinophils were associated with higher risk of RA. Further elucidations of the causality and mechanisms underlying are likely to identify feasible interventions to promote RA prevention.

Abstract Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic synovitis and bone destruction. Proinflammatory cytokines activate pathways of immune-mediated inflammation, which aggravates RA. The mechanistic target of rapamycin (mTOR) signaling pathway associated with RA connects immune and metabolic signals, which regulates immune cell proliferation and differentiation, macrophage polarization and migration, antigen presentation, and synovial cell activation. Therefore, therapy strategies targeting mTOR have become an important direction of current RA treatment research. In the current review, we summarize the biological functions of mTOR, its regulatory effects on inflammation, and the curative effects of mTOR inhibitors in RA, thus providing references for the development of RA therapeutic targets and new drugs.

The structural and cognitive functions of the brain undergo significant changes throughout an individual’s lifetime. The analysis of EEG background waves based on age groups will help reveal the correlation between human cognitive development ability and their age, and provide a new perspective for a deeper understanding of neurodegenerative diseases. Unfortunately, the available literature shows that, in recent years, the analysis of EEG signal background waves at different age groups has been extremely rare. To address the vacuum of this research, this paper introduces an innovative semi-supervised graph attention autoencoder method, SGAAE-AC, an age-based clustering method based on EEG background wave analysis. This method utilizes feedback from the labels generated by age-based clustering to guide the encoder in generating more accurate EEG graph embeddings. Furthermore, by adopting multi-objective optimization techniques, the accuracy and interpretability of EEG signal clustering are significantly improved. Our experimental outcomes elucidate the relationship and impact between human age and EEG background waves from perspectives such as comprehensive EEG spectral activity and frequency band attention, thereby uncovering the patterns of EEG background wave activity as they evolve with age.

Biomass activated carbon was prepared from discarded durian shell and longan shell by KOH chemical activation method, and their adsorption capacity of methylene blue (MB) in water was also investigated. The surface area test (BET), Fourier infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and X-ray diffraction (XRD) were used to characterize the prepared biomass activated carbon, and the effects of activated carbon amount, initial concentration of MB solution, reaction time, temperature and pH on the adsorption of MB were studied. Results indicated that the maximum adsorption capacity of durian shell (longan shell) activated carbon was 363 mg/g under the optimum conditions (initial MB solution concentration of 200 mg/L, carbon amount of 30 mg, pH8.0, 120 min). The specific surface area of durian shell and longan shell activated carbon were 999.63 m2/g and 1377.95 m2/g, respectively, and their average pore sizes were 2.13 nm and 2.20 nm, respectively. In addition, the surface of durian shell and longan shell activated carbon had a large number of pores and a certain laminar structure. The existence of these pores provides rich adsorption sites for activated carbon adsorption, and compared with commercially available activated carbon, it has a more dense pore structure and has a stronger adsorption capacity for methylene blue.

In this study, a real-time dwell scheduling algorithm based on pulse interleaving is proposed for a distributed radar network system. A time pointer vector is introduced to indicate the moment when the dwell task with the highest synthetic priority should be chosen. This task is further allocated to the radar node with the lowest interleaving time utilization ratio, effectively reducing the time gaps during scheduling. Meanwhile, the pulse interleaving analysis determines whether the assigned dwell task can be scheduled successfully on the corresponding radar node. The time slot occupation matrix and energy assumption matrix are introduced to indicate the time and energy resource consumption of radar nodes, which not only simplifies the pulse interleaving analysis process but also enables pulse interleaving among the tasks with different pulse repetition intervals and numbers. Furthermore, to improve the efficiency of dwell scheduling, a threshold of interleaving time utilization ratio is set to adaptively choose the sliding step of the time pointer. The simulation results reveal that the proposed algorithm can execute real-time dwell scheduling for a distributed radar network system and achieve better scheduling performance than the existing dwell scheduling algorithm.

BackgroundA better understanding of the level-grade inflammation for the development and worsening of heart failure (HF) in different gender groups is an unmet need. We performed an updated analysis on the impact of a series of systemic inflammation markers on HF.MethodsThis compensatory cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey (NHANES) 2015-2018. HF was based on the self-reported questions. Univariate and multivariate logistic regression were used to investigate the association between systemic immune-inflammation index (SII), high sensitivity C-reactive protein (hs-CRP), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and HF. For patients of different genders, P for trend was used to analyze potential linear trend relationships and the restricted cubic splines (RCS) were used to describe non-linear relationships. The additive interaction was evaluated by the relative excess risk due to interaction (RERI), attributable proportion (AP), and the synergy index (SI). The multiplicative interaction was evaluated by odds ratio (OR) and 95% confidence interval (CI) of product-term.ResultsA total of 5,830 participants from the NHANES database were divided into two groups: the HF group (n = 210) and the non-HF group (n = 5620). After gender stratification, hs-CRP (OR: 1.01, 95% CI: 1.00-1.03), SII (OR: 1.00, 95% CI: 1.00-1.01), NLR (OR: 1.22, 95% CI: 1.11-1.35) and LMR (OR: 0.79, 95% CI: 0.65-0.93) were independent meaningful factors for HF in males, there was no non-linear relationship between the three factors (SII, NLR, hs-CRP, all P for non-linear > 0.05) and the prevalence of HF, but we detected a non-linear relationship between LMR and the prevalence of HF in males (P for non-linear < 0.05). An additive interaction of hs-CRP and NLR on the risk of HF in males (RERI (OR): 0.67, 95% CI: 0.12-1.34; AP (OR): 0.14, 95% CI: 0.02-0.24; SI (OR): 1.22, 95% CI: 1.03-1.44).ConclusionsIn summary, hs-CRP, NLR, and LMR are superior meaningful markers for HF in males. SII may be a meaningful systemic inflammation warning marker for HF, which needs to be discriminated against with caution. Only detected a non-linear relationship between LMR and the prevalence of HF in males. NLR and hs-CRP may have an additive interaction in the prevalence of male HF patients. The outcome compensated for previous studies that still needed more studies for validation.

As we face increasing challenges of world food security and malnutrition, coarse cereals are coming into favor as an important supplement to human staple foods due to their high nutritional value. In addition, their functional components, such as flavonoids and polyphenols, make them an important food source for healthy diets. However, we lack a systematic understanding of the importance of coarse cereals for world food security and nutritional goals. This review summarizes the worldwide cultivation and distribution of coarse cereals, indicating that the global area for coarse cereal cultivation is steadily increasing. This paper also focuses on the special adaptive mechanisms of coarse cereals to drought and discusses the strategies to improve coarse cereal crop yields from the perspective of agricultural production systems. The future possibilities, challenges, and opportunities for coarse cereal production are summarized in the face of food security challenges, and new ideas for world coarse cereal production are suggested.

Abstract Objective To investigate the clinical efficacy of plasma exchange (PE) with or without prednisone and hydroxychloroquine (HCQ) for the treatment of systemic lupus erythematosus (SLE) during pregnancy. Methods The clinical characteristics of 14 pregnant women with SLE admitted to our hospital were retrospectively analyzed, including 7 only treated with prednisone and HCQ (non‐PE group) as well as 7 combined PE (PE group). The delivery situations of 14 patients were recorded. Data like erythrocyte sedimentation rate (ESR), urine protein, platelet count, and SLEDAI scores were compared between two groups before treatment and 3, 6, and 12 months after delivery. Results Three patients in the non‐PE group ended in miscarriage while all patients in the PE group were delivered successfully. Eleven successfully delivered fetuses in the two groups were healthy, and the Apgar scores were over 8. The ESR of the PE group was significantly lower than that of the non‐PE group at 6 and 12 months after delivery, while there was no statistical difference in ESR between the two groups before treatment and 3 months after delivery. The ESR and urine protein were significantly higher in the non‐PE group at months 3, 6, and 12 postpartum. There was a significant decrease in disease activity postpartum in the PE group compared to predelivery disease activity. The change in platelet counts between the two groups significantly increased over time in the PE group, while SLEDAI scores decreased. Conclusions The combination of PE and oral prednisone and HCQ is possibly a more effective treatment than oral prednisone and HCQ alone for patients with active SLE during pregnancy. This treatment option reduces pregnancy loss and promotes the patients' postpartum condition to a certain extent.

The Standard Model (SM) of particle physics, being a local, unitary and Lorentz-invariant quantum field theory, remains symmetric under the combined action of Charge, Parity, and Time Reversal (CPT) symmetry. This automatically implies that fundamental properties of particles and antiparticles should be equal in magnitude. These fundamental tenets of the CPT principle have been put to stringent tests in recent Penning-trap experiments, where the matter-antimatter mass asymmetry has been measured. In light of these recent advances, we compare the bounds arising on CPT invariance from kaon systems with those from Penning-trap experiments. Using a simple yet powerful argument of mass decomposition of hadrons, we show that bounds on quark-antiquark mass differences from kaon oscillations are way beyond the reach of Penning-trap experiments. We lay out a roadmap to discuss possible reformulations of our understanding of the SM in the case of a discovery of CPT violation by these precision experiments.

Abstract The effective dwell scheduling algorithm must be studied to make full use of the radar system's limited resources. In this study, a real‐time dwell scheduling in phased array radar is investigated, where the optimisation problem model that takes the importance, urgency and desired execution time criteria into consideration is built. A real‐time dwell scheduling algorithm for phased array radar based on a backtracking strategy is proposed to solve this problem. Based on the scheduled task pointed by the time pointer, when it is not interleaved with the previously scheduled tasks, two previously interleaved blocks are backtracked, and the actual execution time of tasks in these two blocks are adjusted. In order to guarantee real‐time scheduling, the concept of the virtual dwell task is introduced to reduce the dimension of the original execution time optimisation problem first, then it is converted into two convex optimisation problems and their analytical solutions are deduced. Simulation results demonstrate that the proposed algorithm can realise real‐time dwell scheduling, and it has the lowest Task Drop Ratio, the highest Hit Value Ratio, Time Utilisation Ratio and low Average Time Shifting Ration compared with conventional and up‐to‐date algorithms.

Abstract Background Cadmium (Cd) is a highly toxic element for plant growth. In plants, hydrogen sulfide (H2S) and methylglyoxal (MG) have emerged as vital signaling molecules that regulate plant growth processes under Cd stress. However, the effects of sodium hydrosulfide (NaHS, a donor of H2S) and MG on Cd uptake, physiological responses, and gene expression patterns of Salix to Cd toxicity have been poorly understood. Here, Salix matsudana Koidz. seedlings were planted in plastic pot with applications of MG (108 mg kg− 1) and NaHS (50 mg kg− 1) under Cd (150 mg kg− 1) stress. Results Cd treatment significantly increased the reactive oxygen species (ROS) levels and malondialdehyde (MDA) content, but decreased the growth parameters in S. matsudana. However, NaHS and MG supplementation significantly decreased Cd concentration, ROS levels, and MDA content, and finally enhanced the growth parameters. Cd stress accelerated the activities of antioxidative enzymes and the relative expression levels of stress-related genes, which were further improved by NaHS and MG supplementation. However, the activities of monodehydroascorbate reductase (MDHAR), and dehydroascorbate reductase (DHAR) were sharply decreased under Cd stress. Conversely, NaHS and MG applications restored the MDHAR and DHAR activities compared with Cd-treated seedlings. Furthermore, Cd stress decreased the ratios of GSH/GSSG and AsA/DHA but considerably increased the H2S and MG levels and glyoxalase I-II system in S. matsudana, while the applications of MG and NaHS restored the redox status of AsA and GSH and further improved glyoxalase II activity. In addition, compared with AsA, GSH showed a more sensitive response to exogenous applications of MG and NaHS and plays more important role in the detoxification of Cd. Conclusions The present study illustrated the crucial roles of H2S and MG in reducing ROS-mediated oxidative damage to S. matsudana and revealed the vital role of GSH metabolism in regulating Cd-induced stress.

This study aims to explore the impact of dual learning on preschool teachers' thriving at work and creative performance, and whether preschool teachers' thriving at work acts as a mediating factor in the relationship between dual learning and teachers' creative work. The participants were preschool teachers from Taiwan. Convenience sampling was used, resulting in a sample size of 388 people. The study results found that preschool teachers' dual learning, which includes both exploitative and exploratory learning, can improve the novelty and usefulness of their work and creativity. Furthermore, the study found that preschool teachers' thriving at work mediates the relationship between dual learning and creativity. This study also discovered that dual learning should combine and complement both exploitative and exploratory learning to achieve balance and the most significant effect. Therefore, it is essential to first help preschool teachers engage in both exploitative and exploratory learning. Schools and kindergartens can also provide relevant courses to help teachers combine these two learning methods. By integrating and complementing their advantages and disadvantages, a balance in learning can be achieved, thereby promoting teachers' creativity in their work.

Candida albicans and Candida glabrata are two common opportunistic fungi that can be co-isolated in oropharyngeal candidiasis (OPC). Hypha is a hallmark of the biofilm formation of C. albicans, indispensable for the attachment of C. glabrata, which is seldom in mycelial morphology. Increasing evidence reveals a hypoxic microenvironment in interior fungal biofilms, reminding of a fact that inflammation is usually accompanied by oxygen deprivation. As a result, it is assumed that the disaggregation of hypha-mediated hypoxia of biofilms might be a solution to alleviate OPC. Based on this hypothesis, sodium houttuyfonate (SH), a well-identified traditional herbal compound with antifungal activity, is used in combination with fluconazole (FLU), a well-informed synthesized antimycotics, to investigate their impact on filamentation in C. albicans and C. glabrata dual biofilms and the underlying mechanism of their combined treatment on OPC. The results show that compared with the single therapy, SH plus FLU can inhibit the hyphal growth in the mixed biofilms in vitro, decrease the fungal burden of oral tissues and internal organs, restore mucosal epithelial integrity and function, and reduce hypoxic microenvironment and inflammation in a mice OPC model. The possible mechanism of the combined therapy of SH plus FLU can be attributed to the regulation of HIF-1α/IL-17A axis through direct abrogation of the dual Candida biofilm formation. This study highlights the role of HIF-1α/IL-17A axis and the promising application of SH as a sensitizer of conventional antifungals in the treatment of OPC.

The study aimed to determine the trends in the manifestations and severity over the epidemic course of imported COVID-19 cases, with comparison to native cases. The clinical characteristics of imported and native Chinese COVID-19 cases included in the study were assessed and compared. The association was analyzed using Mann-Whitney U test for categorical variables, Kruskal-Wallis H test for continuous variables, and Spearman's correlation test for disease severity. A total of 247 imported patients were enrolled, with an average age of 29 years, and 41.3% were female. The imported patients were younger than the native patients (29 vs 47 years) and included a lower proportion of fever (44.1%), chills (5.3%), fatigue (10.1%), leukopenia (14.6%), lymphopenia (39.3%), elevated C-reactive protein (CRP) (7.3%), elevated D-dimer (16.3%), and pneumonia (65.6%). Among patients with moderate severity, imported cases had a lower proportion of fever (44.2%), dyspnea (8.3%), and increased CRP (7.7%) than native cases. COVID-19 infection was less severe in imported cases than that in native cases.

A novel composite electrocatalytic material (CoZ@xCNT), composed of Cobalt-injected cancrinite-structure nanozeolite (CoZ) and carbon nanotubes (CNT), was synthesized successfully. The CoZ was found to possess a cancrinite crystal structure and exhibit nanorod-like morphology. The tight binding between CoZ and CNT was beneficial for the electron transfer. The high-efficiency oxygen evolution reaction (OER) catalytic electrodes (CoZ@xCNT@CC) were prepared, and CoZ@1CNT@CC displayed the largest electrochemical active area, low overpotential of 277 mV and Tafel slope of 86.5 mV·dec−1, and acceptable electrochemical catalytic stability. The combination of CoZ's catalytic ability and CNT's electron transfer ability should contribute to excellent OER catalytic performance.

Tartary buckwheat is a cereal crop that has both medicinal and food origins. However, the underlying factors that contribute to Tartary buckwheat’s flowering and seed-setting characteristics, effective grain formation, and physiological changes are still not well understood. This study aimed to investigate the flowering and seed-setting characteristics of different parts of Tartary buckwheat, as well as the grain-filling characteristics after flowering. To achieve this, Tartary buckwheat cultivars with high (QK3) and low (XQ2) seed-setting rates were selected for pot and field experiments. The study found that Tartary buckwheat undergoes flowering and seed setting simultaneously. Many wilted flowers and grains were observed 45 and 51 d after flowering. Compared to XQ2, QK3 exhibited a higher grain formation rate and seed-setting rate by 7.42% and 26.16%, respectively. Additionally, QK3 had a significantly lower grain abortion rate by 12.03%. The 1000-grain weight and average grain-filling rate of QK3 were 11.10% and 14.81% higher than those of XQ2, respectively. QK3 exhibited a faster maximum grain-filling rate (Rmax), reaching 18.38% faster than XQ2. Additionally, the dry matter average distribution rate in the main stem and branched grains of QK3 was 13.26% and 23.07% higher than that of XQ2, respectively. The sucrose concentration, SS, and SSS enzyme activities of QK3 were all higher than those of XQ2, by 0.29–25.99%, 5.22–11.62%, and 6.64–12.47%, respectively. Correlation analysis revealed a significant positive correlation between sucrose, soluble sugar, and starch concentration during the grain formation process and SS and SSS activities. This suggests that the levels of SS, SSS, soluble sugar, and sucrose in the grain play a crucial role in grain filling.

Abstract We present a generic structure (the layer structure) for decoherence effects in neutrino oscillations, which includes decoherence from quantum mechanical and classical uncertainties. The calculation is done by combining the concept of open quantum system and quantum field theory, forming a structure composed of phase spaces from microscopic to macroscopic level. Having information loss at different levels, quantum mechanical uncertainties parameterize decoherence by an intrinsic mass eigenstate separation effect, while decoherence for classical uncertainties is typically dominated by a statistical averaging effect. With the help of the layer structure, we classify the former as state decoherence (SD) and the latter as phase decoherence (PD), then further conclude that both SD and PD result from phase wash-out effects of different phase structures on different layers. Such effects admit for simple numerical calculations of decoherence for a given width and shape of uncertainties. While our structure is generic, so are the uncertainties, nonetheless, a few notable ones are: the wavepacket size of the external particles, the effective interaction volume at production and detection, the energy reconstruction model and the neutrino production profile. Furthermore, we estimate the experimental sensitivities for SD and PD parameterized by the uncertainty parameters, for reactor neutrinos and decay-at-rest neutrinos, using a traditional rate measuring method and a novel phase measuring method.

Abstract For radar target tracking with non‐linear measurements, a sequential linear filtering method is proposed in this study, which includes a linear filter based on the position measurements and a linear sequential filter based on the range rate measurement. The linear radar measurement equation in the sequential filter is estimated based on the position filtering result. Furthermore, the feedback information during tracking is adaptively selected according to the quality of the angle measurements. When tracking the manoeuvring target, the proposed sequential linear filtering with adaptive information feedback is combined with the interacting multiple model (IMM) framework, and the IMM filter based on sequential linear filtering with adaptive model probability selection is proposed. Simulation results demonstrate the effectiveness of the proposed algorithms in non‐manoeuvring and manoeuvring target tracking. Compared with traditional algorithms, the tracking performance is improved by the proposed algorithms in both typical non‐manoeuvring and manoeuvring scenes.

ABSTRACT: Objectives: Candida albicans is the most clinically prevalent cause of systemic fungal infections in the immunocompromised population. The biofilm-forming ability of C. albicans confers resistance to conventional antifungal agents. The main aim of this study was to investigate the antifungal effects of ethyl caffeate (EC) alone and in combination with fluconazole (FLU) against C. albicans isolates. Methods: The single and combined antifungal activities of EC and FLU were evaluated against planktonic and biofilm cells of C. albicans by the checkerboard assay, time–kill test, crystal violet assay, live/dead staining, rhodamine 6G (R6G) efflux analysis and hydrolase activity. Monotherapy and dual therapy of EC and FLU against systemic candidiasis in a mouse model was also evaluated. Results: The results showed that EC+FLU displayed synergism in 14/26 planktonic C. albicans isolates and 11/26 C. albicans biofilms with fractional inhibitory concentration index (FICI) values ranging between 0.06–0.49 and 0.02–0.38, respectively. Compared with monotherapy, the combination of EC+FLU can markedly inhibit adhesion, yeast-to-hyphae transition, premature and mature biofilm metabolism, hydrolase secretion and drug efflux function of C. albicans Z1407 and Z4935. Moreover, EC can potentiate the antifungal activity of FLU to improve mouse survival, reduce fungal burden and alleviate pathological damage in both C. albicans isolates compared with EC or FLU used alone. Conclusion: EC exhibits a moderate antifungal potential but can be a strong synergist with FLU against C. albicans, highlighting the potential of EC in clinical antifungal therapy as a sensitiser.

Abstract Objective As an autoimmune disease affecting women of reproductive age, systemic lupus erythematosus (SLE) is linked to adverse fetal and maternal outcomes. However, the status of peripheral lymphocytes in SLE patients with different pregnancy outcomes is unclear. This retrospective cross‐sectional study explored the relationship between lymphocyte subpopulations and pregnancy outcomes in married SLE female patients. Methods The absolute numbers of peripheral T, helper T (Th)1, Th2, Th17, regulatory T (Treg), B, and natural killer (NK) cell subpopulations from 585 female SLE patients and 91 female healthy controls (HCs) were assessed. We compared the lymphocyte subpopulations in SLE patients with HCs and analyzed the absolute number and ratio of Treg cells according to pregnancy outcome in SLE patients. Results SLE patients had decreased numbers of T, B, NK, Th1, Th2, Th17, and Treg cells and an imbalance in pro‐ and anti‐inflammatory cells (p

Abstract This study aimed to evaluate the reliability of in vivo confocal microscopic neuroanalysis by beginners using manual and automated modules. Images of sub-basal corneal nerve plexus (SCNP) from 108 images of 18 healthy participants were analyzed by 7 beginner observers using manual (CCMetrics, [CCM]) and automated (ACCMetrics, [ACCM]) module. SCNP parameters analyzed included corneal nerve fiber density (NFD), corneal nerve branch density (NBD), corneal nerve fiber length (NFL), and tortuosity coefficient (TC). The intra-observer repeatability, inter-observer reliability, inter-module agreement, and left–right eye symmetry level of SCNP parameters were examined. All observers showed good intra-observer repeatability using CCM (intraclass correlation coefficient [ICC] > 0.60 for all), except when measuring TC. Two observers demonstrated especially excellent repeatability in analyzing NFD, NBD, and NFL using manual mode, indicating the quality of interpretation may still be observer-dependent. Among all SCNP parameters, NFL had the best inter-observer reliability (Spearman’s rank-sum correlation coefficient [SpCC] and ICC > 0.85 for the 3 original observers) and left–right symmetry level (SpCC and ICC > 0.60). In the additional analysis of inter-observer reliability using results by all 7 observers, only NFL showed good inter-observer reliability (ICC = 0.79). Compared with CCM measurements, values of ACCM measurements were significantly lower, implying a poor inter-module agreement. Our result suggested that performance of quantitative corneal neuroanalysis by beginners maybe acceptable, with NFL being the most reliable parameter, and automated method cannot fully replace manual work.

BackgroundRegulatory T cells (Tregs) have been found to play crucial roles in immune tolerance. However, the status of Tregs in refractory rheumatoid arthritis (RA) is still unclear. Moreover, low-dose interleukin-2 (IL-2) has been reported to selectively promote the expansion of Tregs. This study investigated the status of CD4+ Tregs and low-dose IL-2 therapy in patients with refractory RA.MethodsThe absolute number of CD4+CD25+FOXP3+ Treg (CD4 Treg), CD4+IL17+ T (Th17), and other subsets in peripheral blood (PB) from 41 patients with refractory RA and 40 healthy donors was characterized by flow cytometry combined with an internal microsphere counting standard. Twenty-six patients with refractory RA were treated with daily subcutaneous injections of 0.5 million IU of human IL-2 for five consecutive days. Then, its effects on CD4 Treg and Th17 cells in PB were analyzed.ResultsA decrease in the absolute number of PB CD4 Tregs rather than the increase in the number of Th17 was found to contribute to an imbalance between Th17 and CD4 Tregs in these patients, suggesting an essential role of CD4 Tregs in sustained high disease activity. Low-dose IL-2 selectively increased the number of CD4 Tregs and rebalanced the ratio of Th17 and CD4 Tregs, leading to increased clinical symptom remission without the observed side effects.ConclusionsAn absolute decrease of PB CD4 Tregs in patients with refractory RA was associated with continuing disease activation but not the increase of Th17 cells. Low-dose IL-2, a potential therapeutic candidate, restored decreased CD4 Tregs and promoted the rapid remission of patients with refractory RA without overtreatment and the observed side effects.Clinical trial registrationhttp://www.chictr.org.cn/showproj.aspx?proj=13909, identifier ChiCTR-INR-16009546.

Addressing the challenges of low detection precision and excessive parameter volume presented by the high resolution, significant scale variations, and complex backgrounds in UAV aerial imagery, this paper introduces MFP-YOLO, a lightweight detection algorithm based on YOLOv5s. Initially, a multipath inverse residual module is designed, and an attention mechanism is incorporated to manage the issues associated with significant scale variations and abundant interference from complex backgrounds. Then, parallel deconvolutional spatial pyramid pooling is employed to extract scale-specific information, enhancing multi-scale target detection. Furthermore, the Focal-EIoU loss function is utilized to augment the model’s focus on high-quality samples, consequently improving training stability and detection accuracy. Finally, a lightweight decoupled head replaces the original model’s detection head, accelerating network convergence speed and enhancing detection precision. Experimental results demonstrate that MFP-YOLO improved the mAP50 on the VisDrone 2019 validation and test sets by 12.9% and 8.0%, respectively, compared to the original YOLOv5s. At the same time, the model’s parameter volume and weight size were reduced by 79.2% and 73.7%, respectively, indicating that MFP-YOLO outperforms other mainstream algorithms in UAV aerial imagery detection tasks.

In this work, a highly effective catalyst (MoO3) is synthesized and applied for catalytic wet air oxidation (CWAO) treatment of pharmaceutical wastewater. The catalyst is systematically characterized to investigate the morphology, crystal structure and chemical composition, and the findings demostrated that MoO3 catalyst is successfully synthesized. The degradation mechanism is also illustrated by the density functional theory (DFT) calculation. The degradation experiments confirm that MoO3 catalyst exhibits excellent catalytic performance in CWAO, and the removal rate of TOC (Total Organic Carbon) and COD (Chemical Oxygen Demand) is achieved to more than 93%. The catalyst doses, reaction temperature and reaction time have a significant impact on the removal of pollutants. The degradation process of pollutants in CWAO could be satisfactorily fitted by the second-order kinetics. Besides, MoO3 displays a favorable stability as CWAO catalyst. DFT calculation illustrates that MoO3 catalyst is a typical indirect band gap semiconductor. Moreover, the high temperature environment provides the thermal excitation energy, which favors to the free electrons nearing Fermi level to escape the material surface, and excites them to the conduction band, then directly reduces the pollutants in CWAO. These findings demonstrate that MoO3 can be used as an efficient and excellent catalyst for CWAO of pharmaceutical wastewater.

Abstract Background Idiopathic central precocious puberty (ICPP) reduces patient health-related quality of life (HRQoL). The impacts of disease and treatment on families are also an important concern. This study aimed to assess the association between family impact and HRQoL of children with ICPP. Methods We conducted a case–control study in Chongqing, China. A case group of 134 children with ICPP aged 5–12 years and their caregivers was recruited from a children’s hospital in Chongqing. A total of 210 gender- and age-matched subjects from two primary schools were selected as controls. PedsQLTM4.0 Generic Core Scales (GCS) and PedsQL™ Family Impact Module (FIM) were used in this study. Results Children with ICPP scored lower than controls in all HRQoL domains except physical functioning. In particular, the two groups were significantly different in emotional functioning scores (d = 0.414, P

COVID-19 caused by SARS-CoV-2 has raised a health crisis worldwide. The high morbidity and mortality associated with COVID-19 and the lack of effective drugs or vaccines for SARS-CoV-2 emphasize the urgent need for standard treatment and prophylaxis of COVID-19. The receptor-binding domain (RBD) of the glycosylated spike protein (S protein) is capable of binding to human angiotensin-converting enzyme 2 (hACE2) and initiating membrane fusion and virus entry. Hence, it is rational to inhibit the RBD activity of the S protein by blocking the RBD interaction with hACE2, which makes the glycosylated S protein a potential target for designing and developing antiviral agents. In this study, the molecular features of the S protein of SARS-CoV-2 are highlighted, such as the structures, functions, and interactions of the S protein and ACE2. Additionally, computational tools developed for the treatment of COVID-19 are provided, for example, algorithms, databases, and relevant programs. Finally, recent advances in the novel development of antivirals against the S protein are summarized, including screening of natural products, drug repurposing and rational design. This study is expected to provide novel insights for the efficient discovery of promising drug candidates against the S protein and contribute to the development of broad-spectrum anti-coronavirus drugs to fight against SARS-CoV-2.

BackgroundRheumatoid arthritis is a highly heterogeneous autoimmune disease characterized by unpredictable disease flares and significant differences in therapeutic response to available treatments. One possible reason for poor efficacy is that it cannot be treated accurately due to no optimal stratification for RA patients.ObjectiveThis study aims to construct an RA classification model by m6A characters and further predict response to medication.MethodsTwenty m6A regulators were used to construct a random forest diagnosis model, and RNA-seq analysis was employed for external validation. The RNA modification patterns mediated by 20 m6A regulators were systematically evaluated in 1191 RA samples and explored different molecular clusters associated with other immune microenvironment characteristics and biological pathways. Then, we established an m6A score model to quantify the m6A modification patterns. The model was applied to patients at baseline to test the association between m6Ascore and infliximab responsiveness.ResultsThe m6A diagnosis model showed good discriminatory ability in distinguishing RA. Patients with RA were classified into three clusters with distinct molecular and cellular signatures. Cluster A displayed strongly activated inflammatory cells and pathways. Specific innate lymphocytes occupied cluster B. Cluster C was mainly enriched in prominent adaptive lymphocytes and NK-mediated cytotoxicity signatures with the highest m6A score. Patients with a low m6Ascore exhibited significantly infliximab therapeutic benefits compared with those with a high m6Ascore (p< 0.05).ConclusionOur study is the first to provide a comprehensive analysis of m6A modifications in RA, which provides an innovative patient stratification framework and potentially enables improved therapeutic decisions.

Studies show that non-coding RNAs, especially microRNAs (miRNAs) and circular RNAs (circRNAs), and protein-coding genes are involved in the pathophysiology of multi-organ damage caused by Wilson’s disease (WD). However, circRNA expression profiles and their role in initiation and progression of WD kidney injury remain largely unclear at present. Here, we explored potential critical protein-coding genes, miRNAs, and circRNAs, as well as identify competitive endogenous RNAs (ceRNAs) in a WD mouse model by high-throughput sequencing. We investigated the expression profiles of circRNAs, miRNAs, and protein-coding genes, and identified 32 DEcircRs, 45 DEmiRs, and 1623 DEPs. Identified DEcircRs, DEmiRs, and DEPs were used to construct a ceRNA network, which consisted of 15 DEcircRNAs (four upregulated and 11 downregulated), 18 DEmiRNAs (14 upregulated and four downregulated), and 352 DEmRNAs (205 upregulated and 147 downregulated). Further experiments proved that mmu_circ_0001333 and mmu_circ_0000355 acted as sponges of miR-92b-5p, miR-107-3p, and miR-187-3p to regulate the expression of genes including Smad9, Mapk10, and Aldh3a2, which may participate in WD-related kidney injury. Taken together, this study identified the circRNA/miRNA/mRNA network involved in kidney failure in WD, which may serve as a potential biomarker for the pathogenesis of WD.

Early retention or initial threshold voltage shift (IVS) is one of the key reliability challenges in charge trapping memory (CTM) based 3D NAND flash. Re-program scheme was introduced in quad-level-cell (QLC) NAND (Shibata et al., 2007, Lee et al., 2018, Shibata et al., 2019, and Khakifirooz et al., 2021), and the IVS improvement by re-program scheme was reported. In this work, it is found that re-program can suppress ~81% of IVS in 3D NAND, which is much more significant than that of 2D NAND ~50% (Chen et al., 2010). The mechanisms of IVS improvement by re-program scheme in 3D NAND are investigated. Both vertical de-trapping in the BE-tunneling oxide and charge lateral migration (LM) in the charge-trap layer are suppressed in re-program. Re-program is effective in vertical de-trapping suppression both in checker-board pattern (C/P) and solid-board pattern (S/P) cases, and is effective in LM suppression only in C/P case. Furthermore, the LM improvement by re-program scheme is more pronounced with gate length (Lg) and inter-gate space (Ls) scaling down, showing potential in the reliability improvement of advanced 3D NAND technologies.

Abstract With the continuous progress in electronic devices, thermal interface materials (TIMs) are urgently needed for the fabrication of integrated circuits with high reliability and performance. Graphene as a wonderful additive is often added into polymer to build composite TIMs. However, owing to the lack of a specific design of the graphene skeleton, thermal conductivity of graphene‐based composite TIMs is not significantly improved. Here a chloroform‐assisted method for rapid growth of vertical graphene (VG) arrays in electric field‐assisted plasma enhanced chemical vapor deposition (PECVD) system is reported. Under the optimum intensity and direction of electric field and by introducing the highly electronegative chlorine into the reactor, the record growth rate of 11.5 µm h−1 is achieved and VG with a height of 100 µm is successfully synthesized. The theoretical study for the first time reveals that the introduction of chlorine accelerates the decomposition of methanol and thus promotes the VG growth in PECVD. Finally, as an excellent filler framework in polymer matrix, VG arrays are used to construct a free‐standing composite TIM, which yields a high vertical thermal conductivity of 34.2 W m−1 K−1 at the graphene loading of 8.6 wt% and shows excellent cooling effect in interfacial thermal dissipation of light emitting diode.

The impostor phenomenon (IP) refers to a false internal experience of low intelligence or ability that is associated with anxiety, depression, psychological distress, and burnout. The emotions associated with the IP affect not only personal mental health but also patient care. To address this issue, we need to completely understand the prevalence of and factors related to the IP and ways to resolve/overcome IP feelings. The aim of this scoping review was to identify the existing evidence regarding the IP among nursing students and nurses and determine gaps that can be addressed in future research. We conducted our study based on the scoping review methodological framework proposed by Arksey and O’Malley (2005) and advanced by Levac et al. (2010). After searching the Embase, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science and ProQuest databases, we identified 11 studies for inclusion in this review. We found that while the IP exists in nursing students and nurses, clinical nurse specialist students and final-year nursing students are at significant risk of impostor behavior. We also found that research in the nursing field has focused on the prevalence of and factors related to the IP, but few studies have addressed ways to resolve/overcome IP feelings. Thus, research in this area should be increased. This scoping review presents research gaps that may serve as a starting point for future work on the IP in the nursing field.

Background: Mitochondrial membrane protein–associated neurodegeneration (MPAN) mostly arises as an autosomal recessive disease and is caused by variants in the chromosome 19 open reading frame 12 (C19orf12) gene. However, a few C19orf12 monoallelic truncating de novo variants have been reported and segregated as autosomal dominant traits in some cases.Methods: We performed whole-exome sequencing and analyzed genes related to neurodegeneration associated with brain iron accumulation for pathogenic variants. The identified variants were confirmed by Sanger sequencing and tested using in silico tools.Results: The patient had an onset of depression at the age of 22 years, which rapidly progressed to severe dystonia, dementia, and bladder and bowel incontinence. Neuroimaging showed hypointensity in the substantia nigra and the globus pallidum, with additional frontotemporal atrophy. Genetic analysis revealed a single complex de novo variant [c.336_338delinsCACA (p.Trp112CysfsTer40)] in the C19orf12 gene.Conclusion: This study enriches the genetic spectrum and clinical features of C19orf12 variants and provides additional evidence of the variable inheritance pattern of MPAN.

Ubiquitin specific peptidase 28 (USP28) is closely associated to the occurrence and development of various malignancies, and thus has been validated as a promising therapeutic target for cancer therapy. To date, only few USP28 inhibitors with moderate inhibitory activity have been reported, highly potent and selective USP28 inhibitors with new chemotypes remain to be discovered for pathologically investigating the roles of deubiquitinase. In this current study, we reported the synthesis and biological evaluation of new [1,2,3]triazolo[4,5-d]pyrimidine derivatives as potent USP28 inhibitors. Especially, compound 19 potently inhibited USP28 (IC50 = 1.10 ± 0.02 μmol/L, Kd = 40 nmol/L), showing selectivity over USP7 and LSD1 (IC50 > 100 μmol/L). Compound 19 was cellularly engaged to USP28 in gastric cancer cells. Compound 19 reversibly bound to USP28 and directly affected its protein levels, thus inhibiting the proliferation, cell cycle at S phase, and epithelial-mesenchymal transition (EMT) progression in gastric cancer cell lines. Docking studies were performed to rationalize the potency of compound 19. Collectively, compound 19 could serve as a new tool compound for the development of new USP28 inhibitors for exploring the roles of deubiquitinase in cancers.

Abstract We discuss a novel approach for directional, light dark matter searches inspired by the high precision position measurements achieved in gravitational wave detectors. If dark matter interacts with ordinary matter, movable masses are subject to an effect similar to Brownian motion induced by the scattering with dark matter particles which exhibits certain characteristics and could be observed. We provide estimates for the sensitivity of a hypothetical experiment looking for that motion. Interestingly, if successful, our approach would allow to constrain the local distribution of dark matter momentum.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Decylubiquinone (DUb), a coenzyme Q10 analog, was reported to inhibit breast cancer growth and metastasis by us. However, the influence of DUb on CRC remains unclear. Herein, we found that DUb significantly inhibited CRC growth in the patient-derived xenograft (PDX) and CT26 xenograft models. DUb was further identified to significantly suppress CRC cell proliferation, colony formation, migration and invasion in a dose-dependent manner, while not inhibiting CRC cell apoptosis from flow cytometry assay. Sirtuin2 (SIRT2), a member of the sirtuin protein family, plays a critical role in growth and metastasis in various cancers. Moreover, DUb inhibited CRC progression by upregulating SIRT2. These findings reveal that DUb has the potential to a novel drug for the treatment of CRC by inhibiting CRC cell proliferation.