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Previous ultrasound studies suggest that patients with adenomyosis (AM) exhibit increased uterine cavity stiffness, although direct evidence regarding extracellular matrix (ECM) content and its specific impact on endometrial stiffness remains limited. This study utilized atomic force microscopy to directly measure endometrial stiffness and collagen morphology, enabling a detailed analysis of the endometrium’s mechanical properties: through this approach, we established direct evidence of increased endometrial stiffness and fibrosis in patients with AM. Endometrial specimens were also stained with Picrosirius red or Masson’s trichrome to quantify fibrosis, and additional analyses assessed α-SMA and Ki-67 expression. Studies indicate that pathological conditions significantly influence the mechanical properties of endometrial tissue. Specifically, adenomyotic endometrial tissue demonstrates increased stiffness, associated with elevated ECM and fibrosis content, whereas normal endometrial samples are softer with lower ECM content. AM appears to alter both the mechanical and histological characteristics of the eutopic endometrium. Higher ECM content may significantly impact endometrial mechanical properties, potentially contributing to AM-associated decidualization defects and fertility challenges.

Kawasaki disease is a common systemic vasculitis in children, and early treatment is critical to prevent coronary artery complications. This study aimed to evaluate the impact of different aspirin dosages on the prognosis of Kawasaki disease. A total of 161 children diagnosed with Kawasaki disease were enrolled and divided into four groups based on the dosage of aspirin: 30–34 mg/kg, 35–39 mg/kg, 40–44 mg/kg, and 45–49 mg/kg. Demographic characteristics, pre-treatment laboratory indicators, post-treatment laboratory indicators, the incidence of coronary artery complications, and the rate of IVIG resistance were compared across the groups. No significant differences were found in baseline characteristics such as age, gender, weight, IVIG treatment choice, IVIG treatment duration, or the proportion of patients diagnosed before the age of 1 year. Laboratory indicators before and after treatment were also similar between groups. However, at 3-4 weeks after the onset of illness, the incidence of coronary artery complications was significantly higher in the high-dose aspirin groups compared to the low-dose aspirin group. Additionally, the high-dose aspirin group had a longer duration of fever and a higher proportion of recurrent fever compared to the low-dose group. The results suggest that although aspirin dosage did not appear to have a clear impact on the overall prognosis of Kawasaki disease, high-dose aspirin administered in the 3-4 weeks following disease onset may increase the risk of coronary artery complications and is associated with a higher incidence of recurrent fever. Caution is therefore advised in selecting aspirin dosages to minimize unnecessary risks.

Abstract Background Several randomized clinical trials showed that aspirin could decrease the incidence of preeclampsia (PE) in women at high risk, but data from sources other than traditional clinical trials that investigating the preventive effect of aspirin 75 mg on PE is still lacking, especially in mainland China. We aimed to use Chinese real-world data to estimate the preventive effect of low-dose aspirin (LDA) on PE. Methods Clinical data of pregnant women who were at high risk of PE and had their first prenatal visit at the affiliated Taicang People’s Hospital of Soochow University during November 31, 2018 and May 10, 2021 was retrospectively analyzed. Among the 266 included pregnant women, 115 individuals treated with aspirin 75 mg per day and the other 151 without such treatment were considered as the LDA group and the control group, respectively. Results In the LDA group, 64 (55.65%) of 115 pregnant women took aspirin before 16 weeks of gestation. Besides, 12 (10.43%) and 34 (22.52%) women developed PE in the LDA group and control group, respectively; the aspirin prophylaxis was associated with a lower risk of PE (odds ratio = 0.40, 95% confidence interval = 0.20–0.82, P = 0.0098). In addition, LDA is slightly more effective when initiated before 16 weeks of gestation or in those without chronic hypertension, when compared with their counterparts. Conclusion Prophylaxis with 75 mg per day of aspirin in high-risk women resulted in a significantly lower incidence of PE than that in the control group.

Abstract The authors aimed to explore the association between visit‐to‐visit blood pressure variability (BPV) in pregnant women and adverse neonatal outcomes. The study included 52 891 pregnant women. BPV was calculated as standard deviation (SD) and coefficient of variation (CV) of systolic blood pressure (SBP) or diastolic blood pressure (DBP). All participants were divided into four groups by the quartiles of BPV. When comparing the highest quartiles to the lowest quartiles of DBP SD in all participants, the fully adjusted ORs were 1.19 (95% CI 1.11–1.27, p for trend

A hovercraft can adapt to an ice area, open water, land and other environments, owing to its unique hull structure. It also plays an important role in transporting supplies, rescuing people, breaking ice and conducting other tasks. Ice load prediction is very important for structural safety and navigation of a polar ship, especially in design of air cushion icebreakers or ice breaking platforms. In this paper, based on a simplified circumferential icebreaking pattern, the icebreaking force of the hovercraft operating on the ice sheet at low speed is simulated in a numerical way. Numerical analysis of the icebreaking process with different ice thicknesses and bending strengths are performed. The numerical results are compared with model test data in a time domain for three operating cases. By analyzing the average ice force, the errors between numerical simulation results and model test measurements are less than 30%. The present study is significant for the preliminary design of new icebreaking hovercraft and it assists the operation possibility for existing hovercraft.

In computer vision and pattern recognition applications, there are usually a vast number of unlabelled data whereas the labelled data are very limited. Active learning is a kind of method that selects the most representative or informative examples for labelling and training; thus, the best prediction accuracy can be achieved. A novel active learning algorithm is proposed here based on one‐versus‐one strategy support vector machine (SVM) to solve multi‐class image classification. A new uncertainty measure is proposed based on some binary SVM classifiers and some of the most uncertain examples are selected from SVM output. To ensure that the selected examples are diverse from each other, Gaussian kernel is adopted to measure the similarity between any two examples. From the previous selected examples, a batch of diverse and uncertain examples are selected by the dynamic programming method for labelling. The experimental results on two datasets demonstrate the effectiveness of the proposed algorithm.

Abstract In recent years, the extensive participation of turbine generator in deep peak regulation has caused significant damage to the rotor windings, which is rooted in the frequent and significant changes in the electrical load of the rotor, accompanied by thermal expansion and contraction, causing harm to the rotor insulation and stress fatigue of the metal conductor. Hydrogen, as the cooling medium for the rotor windings of turbine generators, has a direct impact on the windings temperature through its parameters. Starting from suppressing the harm of deep peak regulation on the rotor windings, the inhibitory effect of hydrogen parameter changes on the temperature of the gap‐pickup diagonal‐flow rotor is studied. A calculation model for the rotor temperature field of the turbo‐generator with gap‐pickup diagonal‐flow ventilation is established. The finite volume method is used to iteratively calculate the control equations in the fluid‐thermal‐solid coupling heat transfer problem, and the temperature field distribution of various components of the rotor under different excitation loads is obtained. On this basis, the effects of individual adjustment of hydrogen temperature and pressure, as well as the combined adjustment, on the temperature of the rotor windings are studied. Finally, a variable hydrogen parameter adjustment strategy is proposed for the operation of turbo‐generators under deep peak regulation conditions. To a certain extent, the winding temperature fluctuation can be suppressed, which provides a potential solution for the thermal stable operation of the rotor.

The photo-self-Fenton collaborative system, which combines Fenton reaction with photocatalytic system, exhibits excellent oxidation ability over pollutants without external addition of hydrogen peroxide. Herein, the PDI-C/Fe3+ photo-self-Fenton system, combining carboxylic acid side chain modified perylene diimide supramolecule (PDI-C) and Fe3+, is used to obtain an extremely efficient and durable degradation efficiency of Phenol (a model pollutant in phenolic wastewater). The research systematically investigates the catalytic reaction mechanism by examining the changes in the form and content of iron species, the production mechanism and content changes of hydrogen peroxide and the content changes of various active species. The interaction between Fe3+ and the carboxylic acid side chain of PDI-C promotes photo-generated electron capture by Fe3+ and the resultant conversion to Fe2+, accordingly facilitating the separation of photogenerated carriers. On the other hand, the hydrogen peroxide generated in-situ during the photocatalytic process pairs with the effective circulation of iron ions to form a photo-self-Fenton system, which synergically promotes the efficient and durable phenol degradation. It is also found that as the reaction prolonged, α-FeOOH formed on the surface of PDI-C not only results in iron loss, but also leads to the obscuration of light-absorbing sites, thus becoming a non-negligible factor for the decrease of catalytic activity. Notably, acid addition can not only inhibit the generation of α-FeOOH, but also aid the leaching of formed α-FeOOH, enabling an efficient iron ion circulation and the photo-self-Fenton system's efficient operation. The work also identifies two pathways of hydrogen peroxide production and reveals a competitive relationship between ·OH and ·O2– in the presence of Fe3+. These findings highlight the high efficiency and durability of the PDI-C/Fe3+ photo-self-Fenton system in degrading phenol pollutants under visible light irradiation, while showcasing its potential for practical applications due to its cost-effectiveness and simplicity.

The exceptional energy absorption, deformability, and tuneable Poisson’s ratio properties of negative Poisson’s ratio (NPR) honeycomb biomimetic structures make them highly suitable for applications in aerospace, medical, and acoustic stealth industries. The present study proposes a re-entrant hybrid honeycomb (REHH) structure comprising a re-entrant octagonal unit cell and a re-entrant hexagonal unit cell. Theoretical models of the in-plane elastic modulus and Poisson’s ratio are established based on beam theory, and these models are validated through finite element (FE) simulations and tensile experiments conducted on the REHH samples. The influence of the cell geometry parameters on the in-plane elastic behaviours is investigated. The results indicate that the NPR performance of the REHH structure exhibits superior deformation capability compared with the four-point star hybrid honeycomb (FSHH) structure. The experimental REHH structure samples exhibit significant tensile displacement capabilities in the x-direction.

Abstract There is increasing attention to the production of cellulose nanocrystals (CNCs) from lignocellulosic biomass by enzymatic hydrolysis with cellulase. In this study, the feasibility of the application of a cellulase system from engineered strain Penicillium oxalicum cEES in the production of CNCs was assessed. Using commercial eucalyptus dissolving pulp (EDP) as substrate, the CNCs were successfully obtained by enzymatic hydrolysis with the cellulase cEES, and the total yields of CNCs reached 15.7% through three-step enzymatic hydrolysis of total 72 h (24 h for each step). The prepared CNCs were characterized and found that their crystallinity and thermal stability were higher than that of EDP. In the later stage of enzymatic hydrolysis, the process efficiency of enzymatic preparation of CNCs greatly decreased because of the high crystallinity of cellulosic substrate, and a simple homogenization treatment can promote the enzymatic hydrolysis, as well as produce fusiform CNCs with more uniform size and more fermentable sugar that could be further converted into fuels and bulk chemicals through fermentation. This study provides a feasible enzymatic preparation process for CNCs with engineered cellulase and commercial cellulosic materials. Graphical Abstract

ABSTRACTChina's population and development land have changed dramatically over the last decade. Yet, our understanding of the spatial distribution patterns of the population and built-up areas remains limited. To fill this gap, we employ China's Population Census and GlobeLand30 remote sensing data from 2010 to 2020 at the county level to geovisualize the evolution of the population and built-up area. We find an increasing correlation between built-up areas and population as a result of the urbanization of rural areas, but the rapid expansion of built-up areas has not fundamentally changed concentration of China's population over the period 2010–20.

A series of quaternary ammonium or phosphonium salts were applied as zeolite growth modifiers in the synthesis of hierarchical ZSM-5 zeolite. The results showed that the use of methyltriphenylphosphonium bromide (MTBBP) could yield nano-sized hierarchical ZSM-5 zeolite with a “rice crust” morphology feature, which demonstrates a better catalytic performance than other disinfect candidates. It was confirmed that the addition of MTBBP did not cause discernable adverse effects on the microstructures or acidities of ZSM-5, but it led to the creation of abundant meso- to marco- pores as a result of aligned tiny particle aggregations. Moreover, the generation of the special morphology was believed to be a result of the coordination and competition between MTBBP and Na+ cations. The as-synthesized hierarchical zeolite was loaded with Zn and utilized in the propane aromatization reaction, which displayed a prolonged lifetime (1430 min vs. 290 min compared with conventional ZSM-5) and an enhanced total turnover number that is four folds of the traditional one, owing to the attenuated hydride transfer reaction and slow coking rate. This work provides a new method to alter the morphological properties of zeolites with low-cost disinfectants, which is of great potential for industrial applications.

Abstract Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated nuclease 9 (Cas9) has emerged as a powerful tool to generate targeted loss‐of‐function mutations for functional genomic studies. As a next step, tools to generate genome modifications in a spatially and temporally precise manner will enable researchers to further dissect gene function. Here, we present two heat shock–inducible genome‐editing (IGE) systems that efficiently edit target genes when the system is induced, thus allowing us to target specific developmental stages. For this conditional editing system, we chose the natural heat‐inducible promoter from heat‐shock protein 18.2 (HSP18.2) from Arabidopsis thaliana and the synthetic heat–inducible promoter heat shock–response element HSE‐COR15A to drive the expression of Cas9. We tested these two IGE systems in Arabidopsis using cyclic or continuous heat‐shock treatments at the seedling and bolting stages. A real‐time quantitative polymerase chain reaction analysis revealed that the HSP18.2 IGE system exhibited higher Cas9 expression levels than the HSE‐COR15A IGE system upon both cyclic and continuous treatments. By targeting brassinosteroid‐insensitive 1 (BRI1) and phytoene desaturase (PDS), we demonstrate that both cyclic and continuous heat inductions successfully activated the HSP18.2 IGE system at the two developmental stages, resulting in highly efficient targeted mutagenesis and clear phenotypic outcomes. By contrast, the HSE‐COR15A IGE system was only induced at the seedling stage and was less effective than the HSP18.2 IGE system in terms of mutagenesis frequencies. The presented heat shock–IGE systems can be conditionally induced to efficiently inactivate genes at any developmental stage and are uniquely suited for the dissection and systematic characterization of essential genes.

Shield tunnels are inevitably damaged by complex diseases during operation, so repair and reinforcement are essential. The stainless steel corrugated plate (SSCP) has many advantages for tunnel structure reinforcement because of its high strength, lightweight, convenient construction and installation, and corrosion resistance. Mechanical behaviors of an unreinforced segmental joint and a segmental joint reinforced with a new SSCP were investigated by full-scale tests. The reinforcement test took into account the actual reinforcement conditions in the field, i.e. the joint bore the load alone before reinforcement, maintained the load during reinforcement, and bore the load together with the SSCP after reinforcement. The experimental results demonstrate that: (1) both unreinforced and reinforced joints exhibit a compressive-flexural failure mechanism, and their failure is manifested by concrete crushing in the compressed zone of the joint. (2) Compared to that unreinforced joint, the bending moment and ultimate vertical load of the reinforced one are increased by 73.7% and 119.3%, respectively. And the reinforced joint is stiffer than the unreinforced one, reflecting that SSCP reinforcement enables higher stiffness. (3) Trends of strain-moment curves of the bent bolts and concrete are similar in the unreinforced and reinforced joints. Under the same load, the strains in the reinforced group are smaller than those in the unreinforced group, indicating that the SSCP in the reinforced group shares the load. (4) The strains of the SSCP exhibits a symmetrical distribution in the length direction with the joint section as the symmetrical plane. The strains at the trough show tensile strain, while the strains at the crest show compressive strain. The combined force of the corrugated steel plate cross-section is tensile (i.e., SSCP shares the tension load in the tensile zone of the joint), reflecting the reinforcement effect of SSCP.

Abstract Mixed lineage leukemia 1 (MLL1) is a histone H3 lysine 4 (H3K4) methyltransferase that interacts with WD repeat domain 5 (WDR5) to regulate cell survival, proliferation, and senescence. The role of MLL1 in the pathogenesis of acute kidney injury (AKI) is unknown. In this study, we demonstrate that MLL1, WDR5, and trimethylated H3K4 (H3K4me3) were upregulated in renal tubular cells of cisplatin-induced AKI in mice, along with increased phosphorylation of p53 and decreased expression of E-cadherin. Administration of MM102, a selective MLL1/WDR5 complex inhibitor, improved renal function and attenuated tubular injury and apoptosis, while repressing MLL1, WDR5, and H3K4me3, dephosphorylating p53 and preserving E-cadherin. In cultured mouse renal proximal tubular cells (RPTCs) exposed to cisplatin, treatment with MM102 or transfection with siRNAs for either MLL1 or WDR5 also inhibited apoptosis and p53 phosphorylation while preserving E-cadherin expression; p53 inhibition with Pifithrin-α lowered cisplatin-induced apoptosis without affecting expression of MLL1, WDR5, and H3K4me3. Interestingly, silencing of E-cadherin offset MM102’s cytoprotective effects, but had no effect on p53 phosphorylation. These findings suggest that MLL1/WDR5 activates p53, which, in turn, represses E-cadherin, leading to apoptosis during cisplatin-induced AKI. Further studies showed that MM102 effectively inhibited cisplatin-triggered DNA damage response (DDR), as indicated by dephosphorylation of ataxia telangiectasia mutated (ATM) and ATM and Rad-3 related (ATR) proteins, dephosphorylation of checkpoint kinase 1 and 2 (Chk1 and Chk2); depression of γ-H2AX; and restrained cell cycle arrest, as evidenced by decreased expression of p21 and phospho-histone H3 at serine 10 in vitro and in vivo. Overall, we identify MLL1 as a novel DDR regulator that drives cisplatin-induced RPTC apoptosis and AKI by modulating the MLL1/WDR5-/ATR/ATM-Chk-p53-E-cadherin axis. Targeting the MLL1/WDR5 complex may have a therapeutic potential for the treatment of AKI.

Abstract Background T1 colorectal cancers have a low lymph node metastasis rate and good prognosis. Thus, endoscopic resection is an attractive choice. This study aimed to describe the value of poorly differentiated cluster grade in identifying endoscopically curable T1 colorectal cancers. Methods We included 183 T1 colorectal cancer patients who underwent curative resection. Univariate and multivariate logistic regressions were used to identify lymph node metastasis predictors. The Akaike information criterion was used to determine whether poorly differentiated cluster grade was the best predictor. Backward regression was used to screen the variables. Survival analyses were conducted to determine the prognostic predictive power of poorly differentiated cluster grade. Correlations among predictors and concordance between our pathologists were also investigated. Results Poorly differentiated cluster grade was an independent predictor for lymph node metastasis (adjusted odds ratio [OR]G 3 = 0.001; 95% confidence interval [95% CI]G 3 =

Abstract Corn fiber, a by-product from the corn processing industry, mainly composed of residual starch, cellulose, and hemicelluloses, is a promising raw material for producing cellulosic ethanol and value-added products due to its abundant reserves and low costs of collection and transportation. Now, several technologies for the production of cellulosic ethanol from corn fiber have been reported, such as the D3MAX process, Cellerate™ process, etc., and part of the technologies have also been used in industrial production in the United States. The ethanol yields range from 64 to 91% of the theoretical maximum, depending on different production processes. Because of the multicomponent of corn fiber and the complex structures highly substituted by a variety of side chains in hemicelluloses of corn fiber, however, there are many challenges in cellulosic ethanol production from corn fiber, such as the low conversion of hemicelluloses to fermentable sugars in enzymatic hydrolysis, high production of inhibitors during pretreatment, etc. Some technologies, including an effective pretreatment process for minimizing inhibitors production and maximizing fermentable sugars recovery, production of enzyme preparations with suitable protein compositions, and the engineering of microorganisms capable of fermenting hexose and pentose in hydrolysates and inhibitors tolerance, etc., need to be further developed. The process integration of cellulosic ethanol and value-added products also needs to be developed to improve the economic benefits of the whole process. This review summarizes the status and progresses of cellulosic ethanol production and potential value-added products from corn fiber and presents some challenges in this field at present.

ABSTRACT Epstein-Barr virus (EBV) infects host cells and establishes a latent infection that requires evasion of host innate immunity. A variety of EBV-encoded proteins that manipulate the innate immune system have been reported, but whether other EBV proteins participate in this process is unclear. EBV-encoded envelope glycoprotein gp110 is a late protein involved in virus entry into target cells and enhancement of infectivity. Here, we reported that gp110 inhibits RIG-I-like receptor pathway-mediated promoter activity of interferon-β (IFN-β) as well as the transcription of downstream antiviral genes to promote viral proliferation. Mechanistically, gp110 interacts with the inhibitor of NF-κB kinase (IKKi) and restrains its K63-linked polyubiquitination, leading to attenuation of IKKi-mediated activation of NF-κB and repression of the phosphorylation and nuclear translocation of p65. Additionally, gp110 interacts with an important regulator of the Wnt signaling pathway, β-catenin, and induces its K48-linked polyubiquitination degradation via the proteasome system, resulting in the suppression of β-catenin-mediated IFN-β production. Taken together, these results suggest that gp110 is a negative regulator of antiviral immunity, revealing a novel mechanism of EBV immune evasion during lytic infection. IMPORTANCE Epstein-Barr virus (EBV) is a ubiquitous pathogen that infects almost all human beings, and the persistence of EBV in the host is largely due to immune escape mediated by its encoded products. Thus, elucidation of EBV’s immune escape mechanisms will provide a new direction for the design of novel antiviral strategies and vaccine development. Here, we report that EBV-encoded gp110 serves as a novel viral immune evasion factor, which inhibits RIG-I-like receptor pathway-mediated interferon-β (IFN-β) production. Furthermore, we found that gp110 targeted two key proteins, inhibitor of NF-κB kinase (IKKi) and β-catenin, which mediate antiviral activity and the production of IFN-β. gp110 inhibited K63-linked polyubiquitination of IKKi and induced β-catenin degradation via the proteasome, resulting in decreased IFN-β production. In summary, our data provide new insights into the EBV-mediated immune evasion surveillance strategy.

To apply the discrete element method (DEM) to simulate the interaction process between soda saline–alkali soil and subsoiling component in Northeast China, establishing the soda saline–alkali soil particle model and selecting more accurate simulation parameters are important. In this paper, we studied the soda saline–alkali soil of the Songnen Plain in China. First, we studied the geometric shape of soda saline–alkali soil particles and proposed a modeling method for single soil particles based on the multisphere combination method. Considering the cohesion of soda saline–alkali soil particles, the Hertz–Mindlin with JKR (JKR) model was used as the contact model between soil particles. Then, the calibration method was used to obtain simulation parameters of soils that are difficult to obtain experimentally. We conducted soil angle of repose (AoR) tests, the Plackett–Burman (PB) tests, and steepest ascent (SA) tests in turn to perform a sensitivity analysis for microscopic contact parameters and select the parameters that have a significant effect on the response value (static AoR), i.e., soil surface energy, soil–soil static friction coefficient, and soil–soil rolling friction coefficient. Then, the optimal combination of simulation parameters was obtained via the Box–Behnken (BB) tests, using ANOVA to optimize the multiple regression equation. Finally, the optimal parameter combination was verified by the AoR test and the direct shear (DS) test. The results showed that the parameters had good adaptability for the AoR test. However, the simulation results of the DS test were significantly different from the experimental values. Therefore, the contact model needs to be further modified by adding Bonding bonds between soil particles based on the JKR model and further correcting for Rayleigh time step, shear modulus, and surface energy. By comparing the simulation and the experimental results, it was found that the simulation results obtained from both the DS test and AoR test had relatively small errors relative to physical tests, the two trends are the same, and the values are similar. This verified the feasibility and effectiveness of the soda saline–alkali soil particle modeling method and parameter selection proposed in this paper.

Valproate (valproic acid, VPA), a drug for the treatment of epilepsy and bipolar disorder, causes liver steatosis with enhanced oxidative stress. Accumulating evidences exhibite that gut microbiota plays an important role in progression of nonalcoholic fatty liver disease (NAFLD). However, whether gut microbiota contributes to VPA-caused hepatic steatosis needs to be elucidated. A mixture of five probiotics was selected to investigate their effects on liver steatosis and oxidative stress in mice orally administered VPA for 30 days. Probiotics treatment significantly attenuated the hepatic lipid accumulation in VPA-treated mice via inhibiting the expression of cluster of differentiation 36 (CD36) and distinct diacylglycerol acyltransferase 2 (DGAT2). Meanwhile, probiotics exerted a protective effect against VPA-induced oxidative stress by decreasing the pro-oxidant cytochrome P450 2E1 (CYP2E1) level and activating the Nrf2/antioxidant enzyme pathway. Moreover, VPA treatment altered the relative abundance of gut microbiota at the phylum, family and genera levels, while probiotics partially restored these changes. Spearman's correlation analysis showed that several specific genera and family were significantly correlated with liver steatosis and oxidative stress-related indicators. These results suggest that probiotics exert their health benefits in the abrogation of liver steatosis and oxidative stress in VPA-treated mice by manipulating the microbial homeostasis.

BackgroundThe purpose of this study was to systematically review the effectiveness of regular traditional Chinese fitness exercises on negative emotions and sleep disorders in college students, and to provide evidence-based evidence and new ideas for the negative emotions and sleep disorders among the college students.MethodsA systematic search using 5 English (PubMed, Embase, Scopus, EBSCO, and the Cochrane Library) and 4 Chinese (CNKI, WanFang, VIP, and CBM) databases were initiated to identify randomized controlled trials (RCT) assessing the effect of traditional Chinese fitness exercises on negative emotions and sleep disorders among college students. Standardized mean differences (SMD) and their 95% confidence intervals (CI) were used to determine the pooled effect of the intervention. The Cochrane bias risk assessment tool was used to evaluate the methodological quality and the data were analyzed with Review Manager 5.4.ResultsA total of 12 RCTs were included, including 1,052 subjects. The results showed a potential beneficial effect of traditional Chinese fitness exercises on reducing depression [SMD = −0.93, 95 %CI (−1.76, −0. 10)], anxiety [SMD = −0.74, 95%CI (−0.93, −0.54)], and the sleep disorders [SMD = −2.77, 95%CI (−4.57, −0.97)] symptoms, and these effects were better than in the control group.ConclusionThe findings of this review suggested the traditional Chinese fitness exercises could improve both the negative moods and sleep disorders compared with that of healthy students, the effect on college students with mild to moderate psychological symptoms was obviously improved. The SCL-90 scale is better than the SDS scale in evaluating the improvement effect of traditional Chinese fitness exercises on depression. It was the best intervention program on negative emotions and sleep disorders among college students, with the intervention lasting 5 sessions per week for 30–60 min/session for over 12 weeks.

Fungal cellulases usually contain a family 1 carbohydrate-binding module (CBM1), and its role was considered to recognize the substrate specifically. This study testified that the CBM1s derived from cellobiohydrolase I of Trichoderma reesei, Penicillium oxalicum, and Penicillium funiculosum could be used as an effective accessory protein in cellulase cocktails to enhance the saccharification of lignocellulose, and its enhancement effect was significantly superior to some reported accessory proteins, such as bovine serum albumin (BSA). The promoting effects of the CBM1s were related to not only the CBM1 sources and protein dosages, but also the substrate characteristics and solid consistency during enzymatic hydrolysis. The adsorption capacity of the CBM1s, the adsorption kinetic of TrCBM from T. reesei and cellobiohydrolase, endoglucanase, and β-glucosidase from P. oxalicum, and the effect of adding TrCBM on enzyme activities of free cellulases in the hydrolysis system were investigated, and the binding conformations and affinities of CBM1s to cellulose and lignin were predicted by molecular docking. It was speculated that the higher affinity of the CBM1s to lignin than cellulases could potentially enable the CBM1s to displace cellulase adsorbed on lignin or to preferentially adsorb onto lignin to avoid ineffective adsorption of cellulase onto lignin, which enhanced cellulase system efficiency during enzymatic hydrolysis of lignocellulose.

Shield tunnels inevitably endure various forms of damage as their service times increase. Steel corrugated plates have been used extensively under multiple conditions and have proven effective in strengthening segmental joints, according to full-scale tests. A numerical model is proposed to probe the feasibility of using a new stainless-steel corrugated plate (SSCP) to reinforce shield-tunnel segments. A new method, called virtual-tracking-element technology, is employed to achieve the simulation of a realistic stress state of the segmental joint. Moreover, a segmental-joint-component analysis and a parametric study were conducted based on the numerical model. The results demonstrate that: (1) the virtual-tracking-element technology is a valid and efficient approach to the simulation of the secondary-stress state of segmental joints; (2) SSCP reinforcement is not fully utilized when the grade of segmental concrete is C50, and it has a wide safety margin for potential overload; (3) SSCP reinforcement performs well regardless of the burial depth, and reinforcement in advance is recommended.

Following infestation by Verticillium wilt, alfalfa (Medicago sativa L.) often shows symptoms such as disease spots, leaf loss, stem, and leaf yellowing, resulting in the decline of alfalfa yield and quality and causing significant losses to the alfalfa industry. The popularization and planting of disease-resistant varieties is the most effective method to prevent and control Verticillium wilt of alfalfa. Therefore, it is particularly important to reveal the resistance mechanism of Verticillium wilt resistant varieties of alfalfa. In this study, the physiological and biochemical indexes were measured on days 7, 14, 21, and 28 after inoculation with Verticillium alfalfae for investigating the response mechanisms of two alfalfa varieties, high-resistant WL343HQ, and low-resistant Dryland. Transcriptome sequencing of alfalfa samples infected with V. alfalfae and uninfected alfalfa samples was performed to analyze the potential functions and signaling pathways of differentially expressed genes (DEGs) by GO classification and KEGG enrichment analysis. Meanwhile, weighted gene co-correlation network analysis (WGCNA) algorithm was used to construct a co-expression network of DEGs. Inoculation with V. alfalfae significantly affected net photosynthetic rate, stomatal conductance, chlorophyll content, MDA content, JA and SA concentrations, and NO and H2O2 contents in both WL343HQ and Dryland inoculated with V. alfalfae. Most of the transcription factors in plants were classified in the WRKY, NAC, and bHLH families. WGCNA analysis showed that the number of transcription factors related to plant growth and disease resistance was higher in the corresponding modules of WL343HQ disease groups on days 7 and 28 (WVa) and (WVd) than in the corresponding modules of Dryland disease groups on days 7 and 21 (HVa) and (HVc). These findings provide data for further gene function validation and also provide a reference for in-depth studies on interactions between plants and pathogens.

Danon disease is a rare X-linked dominant genetic disorder that manifests with a clinical triad of cardiomyopathy, skeletal myopathy, and intellectual disability. It is caused by mutations in the lysosome-associated membrane 2 (LAMP2) gene. We report one case of Danon disease and his family members, characterized by ventricular pre-excitation, ventricular hypertrophy, abnormal muscle enzymes, and aberrant liver function. All the patients were confirmed to have Danon disease through genetic screening. Relevant literature was reviewed as a reference for the diagnosis and treatment of the disease.

Radiation belt electron dropouts indicate electron flux decay to the background level during geomagnetic storms, which is commonly attributed to the effects of wave-induced pitch angle scattering and magnetopause shadowing. To investigate the loss mechanisms of radiation belt electron dropouts triggered by a solar wind dynamic pressure pulse event on 12 September 2014, we comprehensively analyzed the particle and wave measurements from Van Allen Probes. The dropout event was divided into three periods: before the storm, the initial phase of the storm, and the main phase of the storm. The electron pitch angle distributions (PADs) and electron flux dropouts during the initial and main phases of this storm were investigated, and the evolution of the radial profile of electron phase space density (PSD) and the (μ, K) dependence of electron PSD dropouts (where μ, K, and L* are the three adiabatic invariants) were analyzed. The energy-independent decay of electrons at L > 4.5 was accompanied by butterfly PADs, suggesting that the magnetopause shadowing process may be the major loss mechanism during the initial phase of the storm at L > 4.5. The features of electron dropouts and 90°-peaked PADs were observed only for >1 MeV electrons at L < 4, indicating that the wave-induced scattering effect may dominate the electron loss processes at the lower L-shell during the main phase of the storm. Evaluations of the (μ, K) dependence of electron PSD drops and calculations of the minimum electron resonant energies of H+-band electromagnetic ion cyclotron (EMIC) waves support the scenario that the observed PSD drop peaks around L* = 3.9 may be caused mainly by the scattering of EMIC waves, whereas the drop peaks around L* = 4.6 may result from a combination of EMIC wave scattering and outward radial diffusion.

Polyethylene glycols (PEGs) in general use are polydisperse molecules with molecular weight (MW) distributed around an average value applied in their designation e.g., PEG 4000. Previous research has shown that PEGs can act as P-glycoprotein (P-gp) inhibitors with the potential to affect the absorption and efflux of concomitantly administered drugs. However, questions related to the mechanism of cellular uptake of PEGs and the exact role played by P-gp has not been addressed. In this study, we examined the mechanism of uptake of PEGs by MDCK-mock cells, in particular, the effect of MW and interaction with P-gp by MDCK-hMDR1 and A549 cells. The results show that: (a) the uptake of PEGs by MDCK-hMDR1 cells is enhanced by P-gp inhibitors; (b) PEGs stimulate P-gp ATPase activity but to a much lesser extent than verapamil; and (c) uptake of PEGs of low MW (5000 Da) occurs by a combination of passive diffusion and caveolae-mediated endocytosis. These findings suggest that PEGs can engage in P-gp-based drug interactions which we believe should be taken into account when using PEGs as excipients and in PEGylated drugs and drug delivery systems.

Abstract Background To compare the efficacy of three types of palliative therapy for advanced hepatocellular carcinoma (HCC), including transarterial chemoembolisation (TACE) monotherapy, sorafenib alone and their combination. Methods The databases of PubMed, Embase and Cochrane Library were retrieved. The odds ratio (OR) with its 95% confidence interval (CI) was used to investigate the binary variables, and the standardised mean difference (SMD) with its 95% CI was employed to evaluate the continuous variables. All statistical tests were performed by using Stata/SE, version 12.0. Results Thirty-one clinical studies, containing 5125 unique cases of patients with advanced HCC, were included. There were significant improvements in overall survival (OS) (pooled SMD = 2.54; 95% CI 1.74–3.34) and time to progression (TTP) (pooled SMD = 2.49; 95% CI 0.87–4.12) of the patients after receiving the combination therapy of TACE and sorafenib, compared to TACE monotherapy, and the OS in the combined treatment cohort was also longer than that in the sorafenib-alone cohort (pooled SMD = 2.92; 95% CI 1.72–4.13). The combination therapy group in comparison to the TACE group benefited a significantly increased overall response rate (ORR) (pooled OR = 2.61; 95% CI 1.43–4.77), 1-year (pooled OR = 2.96; 95% CI 1.71–5.14) and 2-year (pooled OR = 1.64; 95% CI 1.18–2.28) survival rates and reduced disease progression rate (DPR) (pooled OR = 0.47; 95% CI 0.33–0.68); in parallel, the ORR in the group was also significantly higher than that in the sorafenib-alone group (pooled OR = 3.62; 95% CI 1.28–10.22), although without a difference in the DPR (pooled OR = 0.28; 95% CI 0.05–1.48). In addition, we discovered that the 1-year (pooled OR = 1.39; 95% CI 0.84–2.29) and 2-year (pooled OR = 1.70; 95% CI 0.69–4.18) survival rates in the TACE monotherapy cohort were not significantly different to those in the sorafenib-alone cohort. Conclusion The combination therapy is more effective than monotherapy in improving the prognostic outcomes of patients with advanced HCC. Therefore, we recommend it as the preferred treatment intervention for those patients.

Using wave measurements from the EMFISIS instrument onboard Van Allen Probes, we investigate statistically the spatial distributions of the intensity of plasmaspheric hiss waves. To reproduce these empirical results, we establish a fitting model that is a third-order polynomial function of L-shell, magnetic local time (MLT), magnetic latitude (MLAT), and AE*. Quantitative comparisons indicate that the model’s fitting functions can reflect favorably the major empirical features of the global distribution of hiss wave intensity, including substorm dependence and the MLT asymmetry. Our results therefore provide a useful analytic model that can be readily employed in future simulations of global radiation belt electron dynamics under the impact of plasmaspheric hiss waves in geospace.

Corn fiber, a by-product from the corn-processing industry, is an attractive feedstock for cellulosic ethanol because of its rich carbohydrate content (mainly residual starch, cellulose, and hemicellulose), abundant reserves, easy collection, and almost no transportation cost. However, the complex structure and components of corn fiber, especially hemicellulose, make it difficult to be effectively hydrolyzed into fermentable sugars through enzymatic hydrolysis. This study developed a simple and easy industrialized process without detoxification treatment for high-yield ethanol produced from corn fiber. Corn fiber was pretreated by dilute acid under the conditions optimized by Box-Behnken design (0.5% H2SO4 at 105°C for 43 min), and 81.8% of total sugars, including glucose, xylose, and arabinose, could be recovered, then the mixture (solid and hydrolysates) was directly used for semi-simultaneous saccharification and fermentation without detoxification, and ethanol yield reached about 81% of the theoretical yield.

The genome editing toolbox based on CRISPR/Cas9 has brought revolutionary changes to agricultural and plant scientific research. With the development of stable genetic transformation protocols, a highly efficient genome editing system for foxtail millet (Setaria italica) is required. In the present study, we use the CRISPR/Cas9 single- and multi-gene knockout system to target the SiFMBP, SiDof4, SiBADH2, SiGBSS1, and SiIPK1 genes in the foxtail millet protoplasts to screen out highly efficient targeted sgRNAs. Then, we recovered homozygous mutant plants with most of the targeted genes through an Agrobacterium-mediated genetic transformation of foxtail millet. The mutagenesis frequency in the T0 generation was as high as 100%, and it was passed stably on to the next generation. After screening these targeted edited events, we did not detect off-target mutations at potential sites. Based on this system, we have achieved base editing successfully using two base editors (CBE and ABE) to target the SiALS and SiACC genes of foxtail millet. By utilizing CBE to target the SiALS gene, we created a homozygous herbicide-tolerant mutant plant. The current system could enhance the analysis of functional genomics and genetic improvement of foxtail millet.

Unexplained genetic variation that causes complex diseases is often induced by gene-gene interactions (GGIs). Gene-based methods are one of the current statistical methodologies for discovering GGIs in case-control genome-wide association studies that are not only powerful statistically, but also interpretable biologically. However, most approaches include assumptions about the form of GGIs, which results in poor statistical performance. As a result, we propose gene-based testing based on the maximal neighborhood coefficient (MNC) called gene-based gene-gene interaction through a maximal neighborhood coefficient (GBMNC). MNC is a metric for capturing a wide range of relationships between two random vectors with arbitrary, but not necessarily equal, dimensions. We established a statistic that leverages the difference in MNC in case and in control samples as an indication of the existence of GGIs, based on the assumption that the joint distribution of two genes in cases and controls should not be substantially different if there is no interaction between them. We then used a permutation-based statistical test to evaluate this statistic and calculate a statistical p-value to represent the significance of the interaction. Experimental results using both simulation and real data showed that our approach outperformed earlier methods for detecting GGIs.

Among the myriad of statistical methods that identify gene–gene interactions in the realm of qualitative genome-wide association studies, gene-based interactions are not only powerful statistically, but also they are interpretable biologically. However, they have limited statistical detection by making assumptions on the association between traits and single nucleotide polymorphisms. Thus, a gene-based method (GGInt-XGBoost) originated from XGBoost is proposed in this article. Assuming that log odds ratio of disease traits satisfies the additive relationship if the pair of genes had no interactions, the difference in error between the XGBoost model with and without additive constraint could indicate gene–gene interaction; we then used a permutation-based statistical test to assess this difference and to provide a statistical p-value to represent the significance of the interaction. Experimental results on both simulation and real data showed that our approach had superior performance than previous experiments to detect gene–gene interactions.

The CDKN2A (cyclin dependent kinase inhibitor 2A/multiple tumor suppressor 1) gene, also known as the P16 gene, encodes multiple tumor suppressor 1 (MTS1), which belongs to the INK4 family. In tumor tissue, CDKN2A has a high expression level compared with normal tissue and reflects prognosis in tumor patients. Our research targeted the analysis of CDKN2A expression in 33 tumors and clinical parameters, patient prognosis and tumor immunity roles. The CDKN2A expression level was significantly correlated with the tumor mutation burden (TMB) in 10 tumors, and the expression of CDKN2A was also correlated with MSI (microsatellite instability) in 10 tumors. CDKN2A expression was associated with infiltrating lymphocyte (TIL) levels in 22 pancancers, thus suggesting that CDKN2A expression is associated with tumor immunity. Enrichment analysis indicated that CDKN2A expression was involved in natural killer cell-mediated cytotoxicity pathways, antigen processing and presentation, olfactory transduction pathways, and regulation of the autophagy pathway in multiple cancers. CDKN2A was significantly associated with several immune cell infiltrates in pantumors. CDKN2A may serve as a promising prognostic biomarker and is associated with immune infiltrates across cancers.

Grazing is a crucial anthropogenic disturbance on grasslands. However, it is unknown how livestock grazing affects the relationship between biodiversity and productivity of alpine grasslands in Tibet. We carried out a grazing-manipulated experiment from 2016 to 2019 with grazing intensity levels of null (control, grazing exclusion, C.K.), moderate grazing [1.65 standardized sheep unit (SSU) per hectare, M.G.], and heavy grazing (2.47 SSU per hectare, H.G.) on a typical alpine grassland in the Lhasa River Basin, central Tibet. We measured aboveground biomass (AGB), species assembly (alpha and beta diversity indices), and soil nutrients’ availability. The results showed that grazing differently affected plant community in different treatments. Notably, the total dissimilarity value between C.K. and H.G. is 0.334. Grazing decreased the Shannon–Wiener index, increased the Berger–Parker index from 2016 to 2018 significantly, and decreased AGB and total soil nitrogen (STN) significantly. Our results also showed that the grazing affected the relationship between AGB and diversity indices and soil nutrients, including soil organic carbon (SOC) and total soil phosphorus (STP). Specifically, AGB decreased with increasing SOC and STP in all treatments, and heavy grazing changed the positive relationships between AGB, STP, and Shannon–Wiener index to negative correlations significantly compared with grazing exclusion. There was a significant negative correlation between Berger–Parker and Shannon–Wiener indices under each treatment. The general linear models showed that H.G. altered the relationship between diversity and productivity of grassland in central Tibet, and AGB and Shannon–Wiener index positively correlated in C.K. but negatively correlated in H.G. Our study suggests that H.G. caused a negative relationship between plant diversity and productivity. Therefore, sustainable grazing management calls for a need of better understanding the relationship between biodiversity and productivity of alpine grassland in central Tibet.