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Abstract Background Since May 7 2022, mpox has been endemic in many countries which has attracted the attention of health authorities in various countries and made control decisions, in which vaccination is the mainstream strategy. However, the shortage of vaccine doses and the reduction of protective efficacy have led to unresolved issues such as vaccine allocation decisions and evaluation of transmission scale. Methods We developed an epidemiological model to describe the prevalence of the mpox virus in New York City and calibrated the model to match surveillance data from May 19 to November 3, 2022. Finally, we adjusted the model to simulate and compare several scenarios of non-vaccination and pre-pandemic vaccination. Results Relative to the status quo, if vaccination is not carried out, the number of new infections increases to about 385%, and the transmission time will be extended to about 350%, while if vaccinated before the epidemic, the number of new infections decreases to 94.2-96%. Conclusions The mpox outbreak in New York City may be linked to the Pride event. However, with current vaccine coverage, there will be no more large-scale outbreaks of mpox, even if there is another similar activity. For areas with limited vaccines, priority is given to high-risk groups in the age group [34–45] years as soon as possible.

Parameter identification involves the estimation of undisclosed parameters within a system based on observed data and mathematical models. In this investigation, we employ DAISY to meticulously examine the structural identifiability of parameters of a within-host SARS-CoV-2 epidemic model, taking into account an array of observable datasets. Furthermore, Monte Carlo simulations are performed to offer a comprehensive practical analysis of model parameters. Lastly, sensitivity analysis is employed to ascertain that decreasing the replication rate of the SARS-CoV-2 virus and curbing the infectious period are the most efficacious measures in alleviating the dissemination of COVID-19 amongst hosts.

Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such as α-synuclein in neurons. As one of the major intracellular degradation pathways, the autophagy-lysosome pathway plays an important role in eliminating these proteins. Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance of α-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease. Moreover, multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway. Thus, this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease. In this review, we briefly introduce the machinery of autophagy. Then, we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway. Finally, we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.

Abstract Background M2-like tumor-associated macrophages (M2-like TAMs) play key roles in tumor progression and the immune response. However, the clinical significance and prognostic value of M2-like TAMs-associated regulatory genes in gastric cancer (GC) have not been clarified. Methods Herein, we identified M2-like TAM-related genes by weighted gene coexpression network analysis of TCGA-STAD and GSE84437 cohort. Lasso-Cox regression analyses were then performed to screen for signature genes, and a novel signature was constructed to quantify the risk score for each patient. Tumor mutation burden (TMB), survival outcomes, immune cells, and immune function were analyzed in the risk groups to further reveal the immune status of GC patients. A gene-drug correlation analysis and sensitivity analysis of anticancer drugs were used to identify potential therapeutic agents. Finally, we verified the mRNA expression of signature genes in patient tissues by qRT-PCR, and analyzed the expression distribution of these genes by IHC. Results A 4-gene (SERPINE1, MATN3, CD36, and CNTN1) signature was developed and validated, and the risk score was shown to be an independent prognostic factor for GC patients. Further analyses revealed that GC patients in the high-risk group had a worse prognosis than those in the low-risk group, with significant differences in TMB, clinical features, enriched pathways, TIDE score, and tumor microenvironment features. Finally, we used qRT-PCR and IHC analysis to verify mRNA and protein level expression of signature genes. Conclusion These findings highlight the importance of M2-like TAMs, provide a new perspective on individualized immunotherapy for GC patients.

This paper proposed a Filippov blood glucose insulin model with threshold control strategy and studied its dynamic properties. Using Filippov's convex method, we proved the global stability of its two subsystems, the existence and conditions of the sliding region of the system were also given, and different types of equilibrium states of the system were also addressed. The existence and stability of pseudo equilibrium points were thoroughly discussed. Through numerical simulations, we have demonstrated that it is possible to effectively control blood sugar concentrations to achieve more cost-effective treatment levels by selecting an appropriate threshold range for insulin injection.

The microstructure and mechanical properties have a significant impact on the service performance of materials. This paper compared the microstructure and mechanical properties of 2024 aluminum alloy subjected to turning and ultrasonic surface rolling process (USRP). It was found that both turning and USRP can cause grain refinement and increased microhardness. The grain refinement induced by USRP was attributed to dislocation proliferation and T-phase fragmentation; At the same time, a quantitative relationship model between microhardness and microstructure during turning and USRP was constructed. The results showed that precipitation had the greatest impact on the microhardness induced by turning, while dislocations and grain refinement had the greatest impact on the microhardness induced by USRP; In addition, the mechanical performance response mechanism of the materials after turning and USRP was elucidated, and it was found that USRP can significantly enhance the yield strength of the materials.

Objective To make full use of fault log data for diagnosing switch machine faults, a fault diagnosis method based on integrated deep learning is proposed. Method By analyzing the textual data of switch machine faults and combining expert experiences, a two-level fault diagnosis approach is established. The fault text data is preprocessed into machine-readable data, serving as input data for the fault diagnosis model. The principle and method of the CNN-LSTM fault diagnosis model based on the AdaBoost integrated deep learning method are introduced. Result & Conclusion Experimental results demonstrate that under conditions of data class imbalance or limited sample size, the CNN-LSTM model can effectively improve the accuracy of fault diagnosis. Compared with other fault diagnosis models, the CNN-LSTM model performs better. The proposed method is effective and can meet the accuracy requirements of application scenarios.

Objective The aim of this study was to analyze the clinical significance and prognostic value of CD8 + T cell-related regulatory genes in hepatocellular carcinoma (HCC). Methods This was a retrospective study. We combined TCGA-LIHC and single-cell RNA sequencing data for Lasso-Cox regression analysis to screen for CD8 + T cell-associated genes to construct a novel signature. The expression of the signature genes was detected at cellular and tissue levels using qRT-PCR, immunohistochemistry, and tissue microarrays. The CIBERSORT algorithm was then used to assess the immune microenvironmental differences between the different risk groups and a drug sensitivity analysis was performed to screen for potential HCC therapeutic agents. Results An 8-gene CD8 + T cell-associated signature (FABP5, GZMH, ANXA2, KLRB1, CD7, IL7R, BATF, and RGS2) was constructed. Survival analysis showed that high-risk patients had a poorer prognosis in all cohorts. Tumor immune microenvironment analysis revealed 22 immune cell types that differed significantly between patients in different risk groups, with patients in the low-risk group having an immune system that was more active in terms of immune function. Patients in the high-risk group were more prone to immune escape and had a poorer response to immunotherapy, and AZD7762 was screened as the most sensitive drug in the high-risk group. Finally, preliminary experiments have shown that BATF has a promoting effect on the proliferation, migration and invasion of HuH-7 cells. Conclusions The CD8 + T-cell-associated signature is expected to be a tool for optimizing individual patient decision-making and monitoring protocols, and to provide new ideas for treatment and prognostic assessment of HCC.

Orexins are a family of neuropeptides secreted by neurons in the lateral hypothalamus (LH). These peptides act widespreadly across the body by interacting with specific orexin receptors on target cells, which comprise the orexinergic system. Emerging evidence has revealed that the orexinergic system is tightly associated with neuropsychiatric disorders; however, the underlying mechanisms require further exploration. Neuropsychiatric disorders have also been associated with neuroplasticity, while orexins have been shown to play regulatory roles in neuronal plasticity. As such, this review aims to summarize the recent progress of research investigating the roles of the orexinergic system in neuronal plasticity and associated neuropsychiatric disorders, including addiction, depression, and schizophrenia, which may provide novel insights into the mechanism of the orexinergic system in the pathogenesis of these neuropsychiatric disorders.

Groundwater with high concentrations of iron and manganese is harmful to the human body and modern industries. Conventional methods of treating iron and manganese have the disadvantage of high costs and complex control processes. A dielectric barrier discharge (DBD) water treatment system was built to remove iron and manganese from groundwater in this paper. Single-factor experiments were used to analyze the effect of discharge power, initial iron and manganese concentrations, gas flow rate, liquid flow rate, initial pH, flocculant and capture agent process parameters on iron and manganese removal rates. It was found that Fe2+ removal rates can reach 97.31% and Mn2+ removal rates can reach 81.42% when the initial concentrations of Fe2+ and Mn2+ are 6 and 3 mg/L, respectively. The use of 10 mg/L NaHCO3 or 5 mg/L Ca(OH)2 increased the removal rate of Fe2+ to 99% but had no effect on the removal rate of Mn2+. It was found that the optimum treatment time for Mn2+ was different for different process parameters, mainly in the range of 9–15 min, which needs to be noted in future production applications. This work shows that DBD can effectively remove iron and manganese ions from groundwater and analyzes the removal mechanism. HIGHLIGHTS The removal of iron and manganese from groundwater was investigated.; The effect of individual factors on the removal of iron and manganese was analyzed.; DBD removed up to 97.31% of Fe2+.; DBD removed up to 81.42% of Mn2+.;

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

Abstract The fungus Trichoderma reesei is a powerful host for secreted production of proteins. The promoter of cdna1 gene, which encodes a small basic protein of unknown function and high expression, is commonly used for constitutive protein production in T. reesei. Nevertheless, the production level of proteins driven by this promoter still needs to be improved. Here, we identified that the region 600- to 700-bp upstream of the start codon is critical for the efficiency of the cdna1 promoter. Increasing the copy number of this region to three improved the production of a heterologous β-mannanase by 37.5%. Screening of several stressful conditions revealed that the cdna1 promoter is heat inducible. Cultivation at 37 °C significantly enhanced the production of β-mannanase as well as a polygalacturonase with the cdna1 promoter compared with those at 30 °C. Combing the strategies of promoter engineering, multi-copy gene insertion, and control of cultivation temperature, β-mannanase of 199.85 U/mL and relatively high purity was produced in shake flask, which was 6.6 times higher than that before optimization. Taken together, the results advance the understanding of the widely used cdna1 promoter and provide effective strategies for enhancing the production of recombinant proteins in T. reesei. Graphical Abstract

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.

Coinfection is the process of an infection of a single host with two or more pathogen variants or with two or more distinct pathogen species, which often threatens public health and the stability of economies. In this paper, we propose a novel two-strain epidemic model characterizing the co-evolution of coinfection and voluntary vaccination strategies. In the framework of evolutionary vaccination, we design two game rules, the individual-based risk assessment (IB-RA) updated rule, and the strategy-based risk assessment (SB-RA) updated rule, to update the vaccination policy. Through detailed numerical analysis, we find that increasing the vaccine effectiveness and decreasing the transmission rate effectively suppress the disease prevalence, and moreover, the outcome of the SB-RA updated rule is more encouraging than those results of the IB-RA rule for curbing the disease transmission. Coinfection complicates the effects of the transmission rate of each strain on the final epidemic sizes.

Abstract The biomass pretreatment strategies using organic acids facilitate lignin removal and enhance the enzymatic digestion of cellulose. However, lignin always suffers a severe and irreversible condensation. The newly generated C–C bonds dramatically affect its further upgrading. In this study, we used a recyclable hydrotrope (p-Toluenessulfonic acid, p-TsOH) to dissolve lignin under mild condition and stabilized lignin with a quenching agent (formaldehyde, FA) during extraction, achieving both value-added lignin extraction and efficient enzymatic saccharification of cellulose. Approximately 63.7% of lignin was dissolved by 80% (wt. %) p-TsOH with 1.5% FA addition at 80 °C, 30 min. The obtained lignin was characterized by FTIR spectroscopy, TGA, 2D HSQC NMR spectroscopy, and GPC. The results indicated that the extracted lignin exhibited excellent properties, such as light color, a low molecular weight (Mw, 5371 g/mol), and a narrow polydispersity (M w/M n, 1.63). The pretreated substrate was converted to ethanol via a quasi-simultaneous saccharification and fermentation process (Q-SSF). After fermentation of 60 h, the ethanol concentration reached 38.7 ± 3.3 g/L which was equivalent to a theoretical ethanol yield of 82.9 ± 2.2% based on the glucan content, while the residual glucose concentration was only 4.69 ± 1.4 g/L. In short, this pretreatment strategy protected lignin to form new C–C linkages and improved the enzymatic saccharification of glucan for high-titer ethanol production. Graphical Abstract

Emerging infectious diseases are one of the global public health problems which may lead to widespread epidemics and potentially life-threatening infection. Integrated vaccination and physical distancing interventions are two elementary methods for preventing infectious diseases transmission. In this paper, we construct a continuous age-structured model for investigating the transmission dynamics of an emerging infection disease during a short period. We derive the basic regeneration number R0, the spectral radius of the next generation operator K, which determines the disease outbreak or not. Furthermore, we propose an optimal control problem to take account for the cost-effectiveness of social distancing intervention and vaccination. We rigorously obtain sufficient conditions for a L1 control problem. Numerical simulations show that coupling integrated vaccination and physical distancing intervention could effectively eliminate the infection, and such control strategy is more sensitive for people aged 10–39 and over 60.

BackgroundM2-like tumor-associated macrophages (M2-like TAMs) have important roles in the progression and therapeutics of cancers. We aimed to detect novel M2-like TAM-related biomarkers in hepatocellular carcinoma (HCC) via integrative analysis of single-cell RNA-seq (scRNA-seq) and bulk RNA-seq data to construct a novel prognostic signature, reveal the “immune landscape”, and screen drugs in HCC.MethodsM2-like TAM-related genes were obtained by overlapping the marker genes of TAM identified from scRNA-seq data and M2 macrophage modular genes identified by weighted gene co-expression network analysis (WGCNA) using bulk RNA-seq data. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were carried out to screen prognostic genes from M2-like TAM-related genes, followed by a construction of a prognostic signature, delineation of risk groups, and external validation of the prognostic signature. Analyses of immune cells, immune function, immune evasion scores, and immune-checkpoint genes between high- and low-risk groups were done to further reveal the immune landscape of HCC patients. To screen potential HCC therapeutic agents, analyses of gene–drug correlation and sensitivity to anti-cancer drugs were conducted.ResultsA total of 127 M2-like TAM-related genes were identified by integrative analysis of scRNA-seq and bulk-seq data. PDLIM3, PAM, PDLIM7, FSCN1, DPYSL2, ARID5B, LGALS3, and KLF2 were screened as prognostic genes in HCC by univariate Cox regression and LASSO regression analyses. Then, a prognostic signature was constructed and validated based on those genes for predicting the survival of HCC patients. In terms of drug screening, expression of PAM and LGALS3 was correlated positively with sensitivity to simvastatin and ARRY-162, respectively. Based on risk grouping, we predicted 10 anticancer drugs with high sensitivity in the high-risk group, with epothilone B having the lowest half-maximal inhibitory concentration among all drugs tested.ConclusionsOur findings enhance understanding of the M2-like TAM-related molecular mechanisms involved in HCC, reveal the immune landscape of HCC, and provide potential targets for HCC treatment.

Abstract Background Trichoderma reesei is currently the main strain for the commercial production of cellulase. Cellulose induced protein 1 (Cip1) is one of the most abundant proteins in extracellular proteins of T. reesei. Reported literatures about Cip1 mainly focused on the regulation of Cip1 and its possible enzyme activities, but the effect of Cip1 on the enzymatic hydrolysis of lignocellulose and possible mechanism have not still been reported. Results In this study, Cip1 from T. reesei was cloned, expressed and purified, and its effects on enzymatic hydrolysis of several different pretreated lignocellulose were investigated. It was found that Cip1 could promote the enzymatic hydrolysis of pretreated lignocellulose, and the promoting effect was significantly better than that of bovine serum albumin (BSA). And especially for the lignocellulosic substrate with high lignin content such as liquid hot water pretreated corn stover and corncob residue, the promoting effect of Cip1 was even better than that of the commercial cellulase when adding equal amount protein. It was also showed that the metal ions Zn2+ and Cu2+ influenced the promoting effect on enzymatic hydrolysis. The Cip1 protein had no lyase activity, but it could destroy the crystal structure of cellulose and reduce the non-productive adsorption of cellulase on lignin, which partly interpreted the promoting effect of Cip1 on enzymatic hydrolysis of lignocellulose. Conclusion The Cip1 from T. reesei could significantly promote the enzymatic hydrolysis of pretreated lignocellulose, and the promotion of Cip1 was even higher than that of commercial cellulase in the enzymatic hydrolysis of the substrates with high lignin content. This study will help us to better optimize cellulase to improve its ability to degrade lignocellulose, thereby reducing the cost of enzymes required for enzymatic hydrolysis.

Abstract Congenital Heart Defects (CHDs) are associated with different patterns of malnutrition and growth retardation, which may vary worldwide and need to be evaluated according to local conditions. Although tetralogy of Fallot (TOF) is one of the first described CHDs, the etiology outcomes in growth and development of TOF in early age child is still unclear in most cases. This study was designed to investigate the growth retardation status of Chinese pediatric TOF patients under 5 years old. The body height, body weight and body mass index (BMI) of 262 pediatric patients (138 boys and 124 girls) who underwent corrective surgery for TOF between 2014 and 2018 were measured using conventional methods. The average body height, body weight and BMI of the patients were significantly lower than WHO Child Growth Standards, while the most affected was body height. Meanwhile, higher stunting frequency and greater deterioration of both the body height and weight happened in elder age (aged 13–60 months) rather than in infant stage (aged 0–12 months) among these patients. Our results confirmed that intervention should be given at early age to prevent the growth retardation of TOF patients getting severer.

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.

Abstract High efficiency enzymatic hydrolysis of lignocellulose to produce fermentable sugar is important for bioconversion of lignocellulosic biomass to liquid fuels and chemicals. In this study, a simple pretreatment with potassium permanganate is used to enhance the efficiency of organosolv pretreatment of corn stover. It is testified that, compared to the single organosolv pretreatment, the KMnO4 assisted organosolv pretreatment significantly increase yields of carbohydrates through decreasing degradation of hemicellulose, decrease formation of inhibitors and enhance enzymatic hydrolysis of corn stover pretreated at a low pretreatment temperature. Process conditions of the KMnO4 assisted organosolv pretreatment are optimized and the conversion of glucan and xylan in pretreated corn stover at 72 h of enzymatic hydrolysis reach to 89.45% and 85.30% respectively when corn stover is firstly treated with 1% (w/w) KMnO4 at 40°C for 60 min prior to ethanol‐water pretreatment with 50% ethanol concentration at 185°C for 90 min. The differences in morphological feature, fiber surface chemical compositions, crystallinity degree and thermostability of pretreated corn stover by ethanol‐water with and without KMnO4 are characterized by scanning electron microscope, X‐ray photoelectron spectroscopy, X‐ray diffraction and thermogravimetry to explore the underlying reasons of KMnO4 strengthening ethanol‐water pretreatment process.

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.

Aiming at the problem of the helical gears meshing which lead to the fatigue damage and shock of the gear surface， the dynamic performance and modification are analyzed and studied. The dynamics model of helical gears meshing is built based on the impact is affected by the backlash. The coupled model of rigid and flexible is built by Adams， and the angular velocity and load torque of the gear are obtained. Then， the finite element model of helical gear is established， the position and the curve of the maximum contact stress of are obtained. Finally， the angular acceleration， load torque and stress variation curve of the driven gear after modification are obtained by using the arc modification method. The research results indicate that the contact strength is improved based on the short-modification， which can provide the basis for gears analysis， such as， the fatigue life and the transmission efficiency.

We propose an $L_{p}$ -norm-based sparse regularization model for license plate deblurring, which is motivated by distinctive properties of license plate images. For the blurred images, general deblurring methods may restore a good overall visual effect. However, in real-life traffic surveillance system, the deblurring results may be not good for license plates. The main reason lies in that general deblurring methods do not give sufficient thought to the features of license plate, which could be important priors for deblurring. Focusing on this issue, analysis on the statistical distribution characteristics of the license plates are launched, based on which an $L_{p}$ -norm-based regularization model is proposed. Furthermore, alternating direction method of multipliers are introduced to solve the model. Experimental results demonstrate that the proposed model performs favorably against the state-of-the-art license plate image deblurring methods.

Hypercholesterolemia and carotid atherosclerosis contribute to the etiology of stroke. However, there has been a lack of appropriate comorbid animal models incorporating some of the ubiquitous characteristics that precede strokes. Curcumin is a natural active polyphenolic compound extracted from the rhizoma of Curcuma longa L. which possesses comprehensive bioactivities. The present study aimed to evaluate whether neurobehavioral deficits, neuroendocrine-immune dysregulations and cerebral microcirculation dysfunction, are part of the initial stages of cerebral ischemia in individuals suffering from carotid atherosclerosis resulting from a high cholesterol diet (HCD) and if they could be tested using a comorbid animal model. Furthermore, the utility of this model will be examined following the administration of curcumin. Adult wild-type SD rats were fed a regular diet or HCD and supplemented with either vehicle or curcumin for 4 weeks. Carotid injury was induced by an air-drying endothelial denudation method at the end of the second week. Plasma cholesterol, carotid pathomorphology, neurobehavioral tests, and neuroendocrine-immune parameters were measured. We found higher plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), intima and media (I/M) ratio, but lower high-density lipoprotein-cholesterol (HDL-C), spatial learning and memory capacity impairment, elevated NPY expression in the hypothalamus, increased plasma concentration of leptin, upregulated TNF-α, IL-1β, and CRP in the circulation as well as TNF-α and IL-1β in the cerebral cortex, plus enhanced ICAM-1, VCAM-1, and E-selectin in cerebral microvessels in HCD-fed model rats. All these alterations were ameliorated by curcumin. These results suggest that a comorbid rat model was effectively developed by HCD and carotid injury.

Effective pretreatment is vital to improve the biomass conversion efficiency, which often requires the addition of xylanase as an accessory enzyme to enhance enzymatic saccharification of corn stover. In this study, we investigated the effect of two sophisticated pretreatment methods including ammonium sulfite (AS) and steam explosion (SE) on the xylanase profits involved in enzymatic hydrolysis of corn stover. We further explored the interactions between lignin and xylanase Xyn10A protein. Our results showed that the conversion rates of glucan and xylan in corn stover by AS pretreatment were higher by Xyn10A supplementation than that by SE pretreatment. Compared with the lignin from SE pretreated corn stover, the lignin from AS pretreated corn stover had a lower Xyn10A initial adsorption velocity (13.56 vs. 10.89 mg g−1 min−1) and adsorption capacity (49.46 vs. 27.42 mg g−1 of lignin) and weakened binding strength (310.6 vs. 215.9 L g−1). Our study demonstrated the low absolute zeta potential and strong hydrophilicity of the lignin may partly account for relative weak interaction between xylanase protein and lignin from AS pretreated corn stover. In conclusion, our results suggested that AS pretreatment weakened the inhibition of lignin to enzyme, promoted the enzymatic hydrolysis of corn stover, and decreased the cost of enzyme in bioconversion.

Type 2 diabetes mellitus (T2DM) is a complex and heterogeneous disease that primarily results from impaired insulin secretion or insulin resistance (IR). G protein-coupled receptors (GPCRs) are proposed as therapeutic targets for T2DM. GPCRs transduce signals via the Gα protein, playing an integral role in insulin secretion and IR. The regulators of G protein signaling (RGS) family proteins can bind to Gα proteins and function as GTPase-activating proteins (GAP) to accelerate GTP hydrolysis, thereby terminating Gα protein signaling. Thus, RGS proteins determine the size and duration of cellular responses to GPCR stimulation. RGSs are becoming popular targeting sites for modulating the signaling of GPCRs and related diseases. The R4 subfamily is the largest RGS family. This review will summarize the research progress on the mechanisms of R4 RGS subfamily proteins in insulin secretion and insulin resistance and analyze their potential value in the treatment of T2DM.

Catalytic reduction has been regarded as one of the most efficient strategy for organic pollutants removal from aqueous solution. However, lack of efficient catalyst prevents its practical application. Herein, we design a simple and environmental friendly fabrication strategy for the 3D Ag nanoparticles/Ti3C2Tx/polyacrylamide (Ag/MX/PAM) composite hydrogel as high efficient catalyst. In this composite hydrogel, the Ag nanoparticles, Ti3C2Tx (MXene) and polyacrylamide (PAM) act as active species, efficient electron transfer medium and high-capacity adsorbent respectively. Due to these synergistic effects for the composite hydrogel catalyst, the electron-transferring ability as well as the adsorption capacity are boosted and thus high catalytic activity achieves towards both methylene blue (MB) and 4-nitrophenol (4-NP) reduction. The superior rate constant k of 8.333 min−1 and turnover frequency (TOF) up to 25.17 min−1 for 4-NP reduction are realized over the 12%-Ag/MX/PAM hydrogel. Impressively, this composite hydrogel with a foam-like bulk structure can be reused easily after catalytic reaction, making it a potential catalyst for reduction of organic pollutants in industrialization.

Diabetic foot, a main complication of diabetes mellitus, renders the foot susceptible to infection, and may eventually lead to non-traumatic limb amputation due to the deterioration of diabetic foot ulcers (DFUs). Characterizing the pathogen spectrum and antibiotic susceptibility is critical for the effective treatment of DFUs. In the current study, the characteristics and antibiotic susceptibility of the pathogen spectrum were analyzed. Secretions from the DFUs of 102 patients were cultured, and dominant pathogens were identified by using test cards. Antibiotic susceptibility of dominant pathogens was assayed by the Kirby–Bauer assay. We found that the dominant pathogens varied with age, duration of diabetes, blood sugar control, and the initial cause of ulcers. Moreover, the dominant pathogens were susceptible to at least one antibiotic. However, the antibacterial efficacy of several commonly used antibiotics decreased from 2016 to 2019. Our study indicates that the identification of dominant pathogens and antibiotic susceptibility testing is essential for the treatment of DFUs with effective antibiotics, while the abuse of antibiotics should be strictly restrained to reduce the generation of antibiotic-resistant strains.

The amyloid cascade hypothesis has predominately been used to describe the pathogenesis of Alzheimer’s disease (AD) for decades, as Aβ oligomers are thought to be the prime cause of AD. Meanwhile, the neurotrophic factor hypothesis has also been proposed for decades. Accumulating evidence states that the amyloidogenic process and neurotrophic dysfunction are mutually influenced and may coincidently cause the onset and progress of AD. Meanwhile, there are intracellular regulators participating both in the amyloidogenic process and neurotrophic pathways, which might be the common original causes of amyloidogenesis and neurotrophic dysfunction. In this review, the current understanding regarding the role of neurotrophic dysfunction and the amyloidogenic process in AD pathology is briefly summarized. The mutual influence of these two pathogenesis pathways and their potential common causal pathway are further discussed. Therapeutic strategies targeting the common pathways to simultaneously prevent amyloidogenesis and neurotrophic dysfunction might be anticipated for the disease-modifying treatment of AD.

Alzheimer's disease (AD) is the most common type of neurodegenerative disease leading to dementia in the elderly. Increasing evidence indicates that folate plays an important role in the pathogenesis of AD. To investigate the role of folate deficiency/possible deficiency in the risk of AD and the benefical effect of sufficient folate intake on the prevention of AD, a systematic review and meta-analysis were performed. The Web of Science, PubMed, CENTRAL, EBSCO, CNKI, CQVIP, and Wanfang databases were searched. The analysis of cross-sectional studies showed that the standardized mean difference (SMD) was −0.60 (95% confidence interval (CI): −0.65, −0.55), indicating that plasma/serum folate level is lower in AD patients than that in controls. Moreover, the combined odds ratio (OR) of case-control studies was 0.96 (95% CI: 0.93, 0.99), while the combined ORs were 0.86 (95% CI: 0.46, 1.26) and 1.94 (95% CI: 1.02, 2.86) in populations with normal levels of folate (≥13.5 nmol/L) and folate deficiency/possible deficiency (

FES1A is a heat shock protein 70 binding protein. Mutation of FES1A leads to a defect in thermotolerance of Arabidopsis; however, independent fes1a mutants exhibit a range in the extent of thermosensitivity. Here, we found that BRF2, a gene adjacent to FES1A and encoding a component of transcription factor IIIB, affects the thermosensitivity of fes1a mutants. Knockout of BRF2 suppressed fes1a thermosensitivity, while overexpression of BRF2 increased thermosensitivity of fes1a. BRF2 in fes1a mutants regulates the transcriptional strength of RNA Polymerase II and accumulation of heat shock proteins and eventually affects the thermotolerance of fes1a. There is a cross-talking between RNA Pol III and Pol II. The cross-talking is initiated by BRF, magnified by the mutation of FES1A, and finally has an effect on thermotolerance.

Autophagy is an intracellular process that facilitates the bulk degradation of cytoplasmic materials by the vacuole or lysosome in eukaryotes. This conserved process is achieved through the coordination of different autophagy-related genes (ATGs). Autophagy is essential for recycling cytoplasmic material and eliminating damaged or dysfunctional cell constituents, such as proteins, aggregates or even entire organelles. Plant autophagy is necessary for maintaining cellular homeostasis under normal conditions and is upregulated during abiotic and biotic stress to prolong cell life. In this review, we present recent advances on our understanding of the molecular mechanisms of autophagy in plants and how autophagy contributes to plant development and plants’ adaptation to the environment.

Aiming at the problem of the diaphragm coupling is affected by snap loads which lead to diaphragm fatigue broken and fracture failure， the structural and dynamic performance of the redundant diaphragm coupling are carried out. The overall structure of the redundant diaphragm coupling is designed， and the finite element analysis model of diaphragm disk is established， the optimum thickness of the diaphragm meets the design requirement is obtained by calculating. Then， the safety factor of the redundant structure is verified based on the strength analysis of redundant structure of diaphragm coupling， and the transmission of the torque can be realized. Finally， the frequency response curve is obtained based on the dynamic performance research of the diaphragm coupling. The results can provide the effective basis for the analysis of mechanical transmission devices in this field.

Abstract Cellulase (mainly endoglucanase, EG) has been used in pulp modification for improving paper quality through environmentally friendly process. But low activity in alkaline pH and high filter paper activity (FPA) were still obstacles for extending the cellulase application in papermaking industry. In the study, an alkali-tolerant EG gene of Bacillus subtilis Y106 was homologous over-expressed for obtaining suitable enzyme used in pulp modification. The engineering strain could produce the crude enzyme with more alkali-tolerant EG and little PFA. Potential of the crude enzyme in modification of different pulps were investigated. It was found that the enzyme could be used for improving drainage and strength properties of pulps from softwood, hardwood and non-wood materials, especially non-wood pulp such as wheat straw pulp. The underlying mechanisms of pulp modification and different effects on various types of pulps by the EG treatment were also discussed by studying the change in fibers characteristics and fiber bonding.

Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by progressive spatial disorientation, learning and memory deficits, responsible for 60%–80% of all dementias. However, the pathological mechanism of AD remains unknown. Numerous studies revealed that kinin/kinin receptors system (KKS) may be involved in the pathophysiology of AD. In this review article, we summarized the roles of KKS in neuroinflammation, cerebrovascular impairment, tau phosphorylation, and amyloid β (Aβ) generation in AD. Moreover, we provide new insights into the mechanistic link between KKS and AD, and highlight the KKS as a potential therapeutic target for AD treatment.

Ubiquitin-proteasome pathway (UPS) and autophagy-lysosome pathway (ALP) are the two major protein degradation pathways, which are critical for proteostasis. Growing evidence indicates that proteasome inhibition-induced ALP activation is an adaptive response. Transcription Factor EB (TFEB) is a master regulator of ALP. However, the characteristics of TFEB and its role in proteasome inhibition-induced ALP activation are not fully investigated. Here we reported that the half-life of TFEB is around 13.5 h in neuronal-like cells, and TFEB is degraded through proteasome pathway in both neuronal-like and non-neuronal cells. Moreover, proteasome impairment not only promotes TFEB accumulation but also facilitates its dephosphorylation and nuclear translocation. In addition, proteasome inhibition-induced TFEB accumulation, dephosphorylation and nuclear translocation significantly increases the expression of a number of TFEB downstream genes involved in ALP activation, including microtubule-associated protein 1B light chain-3 (LC3), particularly LC3-II, cathepsin D and lysosomal-associated membrane protein 1 (LAMP1). Furthermore, we demonstrated that proteasome inhibition increases autophagosome biogenesis but not impairs autophagic flux. Our study advances the understanding of features of TFEB and indicates that TFEB might be a key mediator of proteasome impairment-induced ALP activation.

Alzheimer’s disease (AD) is the most common form of dementia in the elderly, which is characterized by progressive cognitive impairment. Neuritic plaques, neurofibrillary tangles and neuronal loss are the major neuropathological hallmarks in AD brains. TMP21 is a key molecule for protein trafficking in cells. Growing evidence indicates that TMP21 is dysregulated in AD, which plays a pivotal role in neuritic plaque formation. Therefore, we aim to review the dysregulation of TMP21 in AD, the role of TMP21 in neuritic plaque formation and underlying mechanisms. Moreover, the potential role of TMP21 in neurofibrillary tangle formation, synaptic impairment and neuronal loss is discussed. It will provide an outlook into the potential of regulating TMP21 as a therapeutic approach for AD treatment.

Alkaline polygalacturonate lyase (PGL, EC 4.2.2.2) is an enzyme used in many industries. We developed a fed-batch fermentation process that combines the enzymatic pretreatment of the carbon source with controlling the pH of the fermentative broth to enhance the PGL production from Bacillus subtilis 7-3-3 to decrease the production cost. Maintaining the fermentation broth at pH 6.5 prior to feeding with ammonia and at pH 6.0 after feeding significantly improved PGL activity (743.5 U mL-1) compared with the control (202.5 U mL-1). The average PGL productivity reached 19.6 U mL-1 h-1 after 38 h of fermentation. The crude PGL was suitable for environmentally friendly ramie enzymatic degumming.

Corn stover is a promising feedstock for bioethanol production because of its abundant availability in China. To obtain higher ethanol concentration and higher ethanol yield, liquid hot water (LHW) pretreatment and fed-batch semi-simultaneous saccharification and fermentation (S-SSF) were used to enhance the enzymatic digestibility of corn stover and improve bioconversion of cellulose to ethanol. The results show that solid residues from LHW pretreatment of corn stover can be effectively converted into ethanol at severity factors ranging from 3.95 to 4.54, and the highest amount of xylan removed was approximately 89%. The ethanol concentrations of 38.4 g/L and 39.4 g/L as well as ethanol yields of 78.6% and 79.7% at severity factors of 3.95 and 4.54, respectively, were obtained by fed-batch S-SSF in an optimum conditions (initial substrate consistency of 10%, and 6.1% solid residues added into system at the prehydrolysis time of 6 h). The changes in surface morphological structure, specific surface area, pore volume and diameter of corn stover subjected to LHW process were also analyzed for interpreting the possible improvement mechanism.

Gap junction intercellular communication (GJIC) plays a critical role in the maintenance of corneal endothelium homeostasis. We determined if benzalkonium chloride (BAK) alters GJIC activity in the rabbit corneal endothelium since it is commonly used as a drug preservative in ocular eyedrop preparations even though it can have cytotoxic effects.Thirty-six adult New Zealand albino rabbits were randomly divided into three groups. BAK at 0.01%, 0.05%, and 0.1% was applied twice daily to one eye of each of the rabbits in one of the three groups for seven days. The contralateral untreated eyes were used as controls. Corneal endothelial morphological features were observed by in vivo confocal microscopy (IVCM). Immunofluorescent staining resolved changes in gap junction integrity and localization. Western blot analysis and RT-PCR evaluated changes in levels of connexin43 (Cx43) and tight junction zonula occludens-1 (ZO-1) gene and protein expression, respectively. Cx43 and ZO-1 physical interaction was detected by immunoprecipitation (IP). Primary rabbit corneal endothelial cells were cultured in Dulbecco's Modified Eagle Medium (DMEM) containing BAK for 24 hours. The scrape-loading dye transfer technique (SLDT) was used to assess GJIC activity.Topical administration of BAK (0.05%, 0.1%) dose dependently disrupted corneal endothelial cell morphology, altered Cx43 and ZO-1 distribution and reduced Cx43 expression. BAK also markedly induced increases in Cx43 phosphorylation status concomitant with decreases in the Cx43-ZO-1 protein-protein interaction. These changes were associated with marked declines in GJIC activity.The dose dependent declines in rabbit corneal endothelial GJIC activity induced by BAK are associated with less Cx43-ZO-1 interaction possibly arising from increases in Cx43 phosphorylation and declines in its protein expression. These novel changes provide additional evidence that BAK containing eyedrop preparations should be used with caution to avoid declines in corneal transparency resulting from losses in GJIC activity and endothelial function.

An alkaline polygalacturonate lyase (PGL) from Bacillus subtilis 7-3-3, PelC, with diverse depolymerization abilities for different pectin substrates was found. The PGL activity of PelC decreased with increasing degree of methyl esterification of the substrate. PelA and PelC displayed notable synergistic effects in the enzymatic degumming of ramie fibers. Gum loss rates increased by 62% when PelC was used to replace up to three-eighths of the PelA dose (PelC, 60 U g(-1) ramie fibers). To the best of our knowledge, this study is the first to report the synergistic action of members of polysaccharide lyase families 1 and 3, represented by PelA and PelC, respectively. The present paper provides new insights into the improvement and production of enzymes used in enzymatic degumming.

Vector-host epidemic models with direct transmission are proposed and analyzed. It is shown that the stability of the equilibria in the proposed models can be controlled by the basic reproduction number of the disease transmission. One model considers that the dynamics of human hosts and vectors are described by SIS and SI model, respectively, where the global asymptotical stability for the equilibria of the model is analyzed by constructing Lyapunov function, respectively. The other model considers that the dynamics of the human hosts and vectors are described by SIRS and SI model, respectively, where the global stability of the disease-free equilibrium and the persistence of the disease in the model are also analyzed, respectively.

An age-structured prey-predator model with delays is proposed and analyzed. Mathematical analyses of the model equations with regard to boundedness of solutions, permanence, and stability are analyzed. By using the persistence theory for infinite-dimensional systems, the sufficient conditions for the permanence of the system are obtained. By constructing suitable Lyapunov functions and using an iterative technique, sufficient conditions are also obtained for the global asymptotic stability of the positive equilibrium of the model.