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Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents. The gut microbiota plays an important role in the pathophysiology of NAFLD through the gut–liver axis. Therefore, we aimed to investigate the genus and species of gut microbiota and their functions in children and adolescents with NAFLD. From May 2017 to July 2018, a total of 58 children and adolescents, including 27 abnormal weight (AW) (obese) NAFLD patients, 16 AW non-NAFLD children, and 15 healthy children, were enrolled in this study at Shenzhen Children’s Hospital. All of them underwent magnetic resonance spectroscopy (MRS) to quantify the liver fat fraction. Stool samples were collected and analysed with metagenomics. According to body mass index (BMI) and MRS proton density fat fraction (MRS-PDFF), we divided the participants into BMI groups, including the AW group (n = 43) and the Lean group (n = 15); MRS groups, including the NAFLD group (n = 27) and the Control group (n = 31); and BMI-MRS 3 groups, including NAFLD_AW (AW children with NAFLD) (n = 27), Ctrl_AW (n = 16) (AW children without NAFLD) and Ctrl_Lean (n = 15). There was no difference in sex or age among those groups (p > 0.05). In the BMI groups, at the genus level, Dialister, Akkermansia, Odoribacter, and Alistipes exhibited a significant decrease in AW children compared with the Lean group. At the species level, Megamonas hypermegale was increased in the AW group, while Akkermansia muciniphila, Dialister invisus, Alistipes putredinis, Bacteroides massiliensis, Odoribacter splanchnicus, and Bacteroides thetaiotaomicron were decreased in AW children, compared to the Lean group. Compared with the Control group, the genus Megamonas, the species of Megamonas hypermegale and Megamonas rupellensis, increased in the NAFLD group. Furthermore, the genus Megamonas was enriched in the NAFLD_AW group, while Odoribacter, Alistipes, Dialister, and Akkermansia were depleted compared with the Ctrl_Lean or Ctrl_AW group at the genus level. Megamonas hypermegale and Megamonas rupellensis exhibited a significant increase in NAFLD_AW children compared with the Ctrl_Lean or Ctrl_AW group at the species level. Compared with healthy children, the pathways of P461-PWY contributed by the genus Megamonas were significantly increased in NAFLD_AW. We found that compared to healthy children, the genus Megamonas was enriched, while Megamonas hypermegale and Megamonas rupellensis were enriched at the species level in children and adolescents with NAFLD. This indicates that the NAFLD status and/or diet associated with NAFLD patients might lead to the enrichment of the genus Megamonas or Megamonas species.

Abstract Many common pathogens are difficult or impossible to detect using conventional microbiological tests. However, the rapid and untargeted nature of metagenomic next-generation sequencing (mNGS) appears to be a promising alternative. To perform a systematic review and meta-analysis of evidence regarding the diagnostic accuracy of mNGS in patients with infectious diseases. An electronic literature search of Embase, PubMed and Scopus databases was performed. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Summary receiver operating characteristics (sROC) and the area under the curve (AUC) were calculated; A random-effects model was used in cases of heterogeneity. A total of 20 papers were eligible for inclusion and synthesis. The sensitivity and specificity of diagnostic mNGS were 75% and 68%, respectively. The AUC from the SROC was 85%, corresponding to excellent performance. mNGS demonstrated satisfactory diagnostic performance for infections and yielded an overall detection rate superior to conventional methods.

Objective: To evaluate the effect of low-glycemic index (GI) noodles on improving glucose and lipid metabolism in diabetic mice induced by streptozotocin (STZ). Methods: Diabetic male Kunming mice were induced by STZ, the intervention group was fed with low GI noodles for 7 weeks, the glucose and lipid metabolism index were measured, and compared with the model control group fed with normal noodles. Results: Compared with the diabetic mice in the model group, the body weight, serum insulin (INS) and liver glycogen levels increased significantly (P

To solve the problem of inaccurate prediction of the stack life of proton exchange membrane fuel cells, this paper first proposed a fuel-cell aging prediction method based on method Savitzky–Golay Smoothing and Group Method of Data, which was based on the data drive. Savitzky–Golay Smoothing is an optimal piecewise fitting method based on polynomial in the time domain and using the least square method through moving window, which is widely used in data flow smoothing and denoising. Group Method of Data is a modeling method of the complex nonlinear dynamic system. The inner criterion and outer criterion are used in the training set and test set respectively, and the optimal solution is finally solved by iterative screening. The method presented in this paper was verified by 1020 h fuel cell aging experiment. The experimental results show that: the MSE, RMSE, R of the test data are respectively 6.3935e−05, 0.0079959, and 0.99616. The data-driven prediction method proposed in this paper can be used for fuel cell aging prediction and fault warning.

Severe Community Acquired Pneumonia (SCAP) challenges public health globally. Considerable improvements in molecular pathogen testing emerged in the last few years. Our prospective study combinedly used traditional culture, antigen tests, PCR and mNGS in SCAP pathogen identification with clinical outcomes. From June 2018 to December 2019, we conducted a multi-centre prospective study in 17 hospitals of SCAP patients within 48 hours of emergency room stay or hospitalization in China. All clinical data were uploaded into an online database. Blood, urine and respiratory specimens were collected for routine culture, antigen detection, PCR and mNGS as designed appropriately. Aetiology confirmation was made by the local attending physician group and scientific committee according to microbiological results, clinical features, and response to the treatment. Two hundred seventy-five patients were included for final analysis. Combined detection methods made identification rate up to 74.2% (222/299), while 14.4% (43/299) when only using routine cultures and 40.8% (122/299) when not using mNGS. Influenza virus (23.2%, 46/198), S. pneumoniae (19.6%, 39/198), Enterobacteriaceae (14.6%, 29/198), Legionella pneumophila (12.6%, 25/198), Mycoplasma pneumoniae (11.1%, 22/198) were the top five common pathogens. The in-hospital mortality of patients with pathogen identified and unidentified was 21.7% (43/198) and 25.9% (20/77), respectively. In conclusion, early combined detection increased the pathogen identification rate and possibly benefitted survival. Influenza virus, S. pneumoniae, Enterobacteriaceae was the leading cause of SCAP in China, and there was a clear seasonal distribution pattern of influenza viruses. Physicians should be aware of the emergence of uncommon pathogens, including Chlamydia Psittaci and Leptospira.

This work described the one-pot synthesis of orange pectin encapsulated Fe3O4 nanoparticles (Fe3O4@Pectin NPs) which is prepared by co-precipitation of Fe(II/(III) ions in alkaline solution mediated by pectin. This process led to formation of magnetic nanoparticles within the network of pectin. Physicochemical characterization of the as-synthesized Fe3O4@Pectin NPs was carried out through Fourier transformed infrared spectroscopy (FT-IR), electron microscopy (SEM and TEM), energy dispersive X-ray spectroscopy (EDX), vibrating sample magnetometer (VSM) and X-ray diffraction (XRD). The in vitro cytotoxic and anti-liver cancer effects of biologically synthesized Fe3O4@Pectin NPs against pleomorphic hepatocellular carcinoma (SNU-387), hepatic ductal carcinoma (LMH/2A), morris hepatoma (McA-RH7777), and novikoff hepatoma (N1-S1 Fudr) cancer cell lines were assessed. The anti-liver cancer properties of the Fe3O4@Pectin NPs could significantly remove pleomorphic hepatocellular carcinoma (SNU-387), hepatic ductal carcinoma (LMH/2A), morris hepatoma (McA-RH7777), and novikoff hepatoma (N1-S1 Fudr) cancer cell lines in a time and concentration-dependent manner by MTT assay. The IC50 of the Fe3O4@Pectin NPs were 8, 13, 10, and 7 µg/mL against pleomorphic hepatocellular carcinoma (SNU-387), hepatic ductal carcinoma (LMH/2A), morris hepatoma (McA-RH7777), and novikoff hepatoma (N1-S1 Fudr) cancer cell lines. The antioxidant activity of Fe3O4@Pectin NPs was determined by DPPH method. The Fe3O4@Pectin NPs showed the high antioxidant activity according to the IC50 value. It seems that the anti-human liver cancer effect of recent nanoparticles is due to their antioxidant effects.

Objective: Aiming at the high incidence of chronic diseases such as obesity and diabetes, a kind of multigrain steamed bun with low glycemic index (GI) was prepared. Methods: Considering the factors of reducing GI, the whole wheat flour and buckwheat flour were used as the main raw materials, combined with pomelo, whole chia seeds, inulin, as well as the starch retrogradation treatment to make multigrain steamed bun. GI value, sensory evaluation, texture properties and resistant starch (RS) were taken as evaluation indexes. Results: The best method for processing low GI steamed bun was as follows: Taking whole wheat flour and buckwheat flour with the ratio of 7:3 as steamed bun mixed flour, 30% whole chia seeds and 9% inulin were added into the mixture, 40% pomelo was used to replace part of the dough water, and refrigerated the steamed bun at 4 ℃ for 24 h. The multigrain steamed bun prepared under this condition had a regular shape, smooth and shiny surface with good chewiness, with a resistant starch content of 1.61% and a sensory score of 85.30. The GI value was 53.98, which was 38.9% lower than that of the traditional steamed bun, and met the requirements of low GI food. Conclusion: This process could not only greatly reduce the GI value of steamed bun, but also ensure good taste of the product, which could provide a reference for the development of low GI foods.

Structural protection method,protective layer method,protective layer material,electrochemical protection method and medium treatment method are the main methods for metal corrosion prevention.Among many corrosion inhibition methods,protective layer material anti-corrosion method is an economical,efficient and widely used anti-corrosion method.Epoxy resin is an efficient protective layer material,which can be used after curing at room temperature or heating.However,the micropores in the curing process may weaken the corrosion resistance of epoxy coating.Therefore,adding nanomaterials into epoxy resin to form epoxy resin composite coating can fill the micropores in epoxy coating,thus improving the anti-corrosion efficiency of epoxy coating.Firstly,the factors affecting the corrosion resistance of nanomaterials/epoxy composite coating were introduced in detail,and the corrosion resistance mechanisms of nanomaterial/epoxy composite coating were discussed.In addition,two kinds of nanomaterials (graphene and metal-organic framework materials) used for epoxy coating were briefly introduced,and the modification methods of graphene and metal-organic framework materials were summarized.Finally,the problem in application and the development prospect of nanomaterials/epoxy composite coating were prospected from the aspects of resin composition,filler composition,mechanism exploration and development of self-healing coating,and it was pointed out that nanomaterials/epoxy composite coating is a long-term method to protect metals from corrosion,and two-dimensional and three-dimensional materials for epoxy coatings should be developed in the future.

Abstract Based on nighttime light data and statistical data, this study calculated the level of urban–rural integration (URI) of Shandong province, researched spatial heterogeneity of URI levels by local spatial autocorrelation analysis, Geodetector, and geographically weighted regression, and analyzed its influencing factors and spatial heterogeneity. The results concluded that: (1) The spatial pattern of urban–rural integrated level is consistent with the level of regional economic development in Shandong province. The level of URI is higher along the Qingdao–Jinan railway and along the coast, whereas the level is lower in southwest Shandong and northwest Shandong. (2) The cities of Yantai and Weifang are High–High cluster areas of urban integration, and Jining is a Low–Low cluster area. The spatial agglomeration characteristics are not significant in other cities. (3) Among the main factors affecting URI, the explanatory power of the rural population with high school or technical secondary school education or above, the area of urban construction land, and the secondary and tertiary industry GDP to the spatial pattern of URI in Shandong province are 73.58%, 62.08%, and 58.66%, respectively. As the key factors, spatial heterogeneity, such as north–south differences, southwest-to-northeast differences, and east–west differences, is evident.

In order to reflect the creep characteristics of unsaturated silty clay, a triaxial compression consolidation drainage creep test was conducted under the condition of controlling the matric suction. According to the results of the creep test, combined with the empirical models, Mesri model and Log-modified model, the relationship between the initial tangent modulus and the matric suction was established, and two empirical models of unsaturated soil creep considering the effect of matric suction were constructed. The study confirmed the stress–strain through the ε/D–ε relationship curve, and determined the parameters F and n through power function. The methods for determining the strain–time relationship parameters of the two improved models are different. The improved Mesri model was obtained by fitting the ln ε–ln t relationship, while the improved Log-modified model was solved by the BFGS algorithm and the general global optimization method. By comparing the two improved models of unsaturated soil creep tests, it was found that the improved Mesri model can more accurately describe the creep characteristics of unsaturated soils, which confirms the rationality and feasibility of this model and method.

ObjectivesThis research aims to investigate if cataract extraction lowers the risk of all-cause dementia.MethodsOriginal literature on cataract surgery associated with all-cause dementia as of November 27, 2022, was searched in several commonly used databases. Manual review was used to include eligible studies. Stata software (version 16) was used to perform statistical analysis on pertinent data. Publication bias can be precisely evaluated using funnel plots and Egger's test.ResultsIn the meta-analysis of 4 cohort studies with 245,299 participants. Pooled analysis indicated that cataract surgery was linked to a lower incidence of all-cause dementia (OR = 0.77, 95%CI: 0.66–0.89; I2= 54.7%; P < 0.001). Cataract surgery was linked to a lower risk of AD (OR = 0.60, 95%CI: 0.35–1.02; I2= 60.2%; P < 0.001).ConclusionsCataract surgery is linked to a lower incidence of all-cause dementia and Alzheimer's disease. A cataract is a reversible visual impairment. Cataract surgery may be a protective factor against the onset of all-cause dementia and can reduce the economic and family burden caused by all-cause dementia worldwide. Given the restricted pool of included studies, our findings necessitate meticulous interpretation.Systematic review registrationhttp://www.crd.york.ac.uk/prospero retrieve registration details by searching CRD4202379371.

IntroductionTo investigate the effects of no-tillage with straw mulching on the absorption and utilization of soil nitrogen (N), fertilizer N, and straw N by rice under paddy-upland rotations.MethodsA field experiment with three cropping systems: fallow–rice rotation without straw mulching (FRN), wheat–rice rotation with wheat mulching in rice season (WRS), and oilseed rape–rice rotation with oilseed rape straw mulching in rice season (ORS) was conducted from 2015 to 2017, along with a mini-plot experiment with 15N-labeled urea and straws, which was conducted in 2017.ResultsNo-tillage with straw reduced rice N uptake up to 20 days after transplanting, the total amount of fertilizer N uptake of WRS and ORS rice plants was 46.33 and 61.67 kg/ha, respectively, which was 9.02 and 45.10% higher than that of FRN plants. Soil N was the main source for rice growth, followed by fertilizer N. Soil N uptake by WRS and ORS rice plants was 21.75 and 26.82% higher than that of FRN plants, accounting for 72.37 and 65.47%, respectively, of the total N accumulated in rice plants. Straw mulching increased the N utilization efficiency of tillering, panicle, and total fertilizer by 2.84–25.30%; however, base fertilizer was dependent on straw mulching. The total amount of N released from WRS and ORS straw mulching in the rice season was 34.97 and 24.82 kg/ha, respectively; however, only 3.04 and 4.82% of it was absorbed by the rice plants, accounting for only 0.62 and 0.66% of the total accumulated N.DiscussionNo-tillage with straw mulching under paddy-upland rotations increased the N utilization of rice, especially for the absorption of soil N. These results provide theoretical information for the effective utilization of straw and rational N application practices in rice-based cropping systems.

Inflammatory bowel disease (IBD) mainly includes Crohn’s disease and ulcerative colitis. These diseases have a progressive course of chronic relapse and remission and affect a large number of children and adults worldwide. The burden of IBD is rising worldwide, with levels and trends varying greatly in countries and regions. Like most chronic diseases, the costs associated with IBD are high, including hospitalizations, outpatient and emergency visits, surgeries, and pharmacotherapies. However, there is no radical cure for it yet, and its therapeutic targets still need further study. Currently, the pathogenesis of IBD remains unclear. It is generally assumed that the occurrence and development of IBD are related to the environmental factors, gut microbiota, immune imbalance, and genetic susceptibility. Alternative splicing contributes to a various diseases, such as spinal muscular atrophy, liver diseases, and cancers. In the past, it has been reported that alternative splicing events, splicing factors, and splicing mutations were associated with IBD, but there were no reports on the practical application for clinical diagnosis and treatment of IBD using splicing-related methods. Therefore, this article reviews research progress on alternative splicing events, splicing factors, and splicing mutations associated with IBD.

Abstract. Immunotherapies targeting cancer neoantigens are safe, effective, and precise. Neoantigens can be identified mainly by genomic techniques such as next-generation sequencing and high-throughput single-cell sequencing; proteomic techniques such as mass spectrometry; and bioinformatics tools based on high-throughput sequencing data, mass spectrometry data, and biological databases. Neoantigen-related therapies are widely used in clinical practice and include neoantigen vaccines, neoantigen-specific CD8+ and CD4+ T cells, and neoantigen-pulsed dendritic cells. In addition, neoantigens can be used as biomarkers to assess immunotherapy response, resistance, and prognosis. Therapies based on neoantigens are an important and promising branch of cancer immunotherapy. Unremitting efforts are needed to unravel the comprehensive role of neoantigens in anti-tumor immunity and to extend their clinical application. This review aimed to summarize the progress in neoantigen research and to discuss its opportunities and challenges in precision cancer immunotherapy.

Abstract The mass production of disposable polyolefin products has led to serious plastic pollution and an imbalance between manufacturing and recycling. Given these challenges, the chemical upcycling of waste polyolefins has attracted extensive attention due to its high efficiency and economic benefits. Herein, we review the development of polyolefin chemical upcycling in heterogeneous catalysis. The status quo of polyolefin recycling is first discussed. We then introduce the advanced strategies for chemical upcycling in the view of different value‐added products and discuss their challenges and prospects. Our in‐depth analysis centers on the catalytic mechanism and the design principle of heterogeneous catalysts. Finally, we outlook the promising directions to facilitate the degradation process via polymer and catalyst design and optimized catalytic engineering. Innovative strategies are expected to promote the chemical upcycling of polyolefins, bringing great promise for the sustainable development of society.

Abstract Background The surveillance and therapy of early-stage cancer would be better for patients’ prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterization of early-stage cancer. Therefore, we focused on and presented comprehensive proteomic and phosphoproproteomic profiling of the trace FFPE samples from early-stage gastrointestinal cancer, and then explored the potential biomarkers of early-stage gastrointestinal cancer. Methods In this study, a quantitative proteomic method with chromatography with mass spectrometry (LC-MS/MS) was used to analyse the proteomic difference between the trace early-stage esophageal squamous cell carcinoma (EESCC) and early-stage duodenum adenocarcinoma cancer (EDAC). Results We identified ~ 6000 proteins and > 10,000 phosphosites in single trace FFPE samples. Comparative analysis disclosed the diverse proteomic features of tumor tissues compared with paired normal tissue of EESCC and EDAC, and revealed the difference of EESCC and EDAC was derived from their origin normal tissue. The distinct separation of EESCC and EDAC illustrated the functions of cell cycle (RB1 T373, EGFR T693) in EESCC, and the positive impacts of apoptosis, metabolic processes (MTOR and MTOR S1261) in EDAC. Furthermore, we deconvoluted the immune infiltration of early-stage gastrointestinal cancer, in which higher immune cell signatures were detected in EDAC, and showed the specific cytokines in EESCC and EDAC. We performed kinases-substates relationship analysis and elucidated the specific proteomic kinase characterization of EESCC and EDAC, and proposed the medicative effects and corresponding drugs for EESCC and EDAC at the clinic. Conclusion We disclosed the specific immune characterization of the early-stage gastrointestinal cancer, and presented potential makers of EESCC (EGFR, PDGFRB, CDK4, WEE1) and EDAC (MTOR, MAP2K1, MAPK3). This study represents a major stepping stone towards investigating the carcinogenesis mechanism of gastrointestinal cancer, and providing a rich resource for medicative strategy in the clinic. Graphical Abstract

Abstract Supramolecular polymers are materials that exhibit a range of functionalities and thus find wide applicability. In this study, two natural low‐molecular‐weight compounds, thioctic acid (TA) and phytic acid (PA), are used to fabricate polymeric supramolecular structures. The coexistence of dynamically covalently linked poly(TA) and hydrogen bond linked poly(PA) moieties result in copolymeric materials with different dynamic features. The obtained poly(TA‐PA)s show rapid and strong adhesion on a variety of natural and artificial surfaces, with high 180° peeling, lap‐shear, and pull‐off strengths over wide temperature (−18 °C to 60 °C) and humidity (20−99%) ranges. The poly(TA‐PA)s also display good stability and adhesion in the presence of water, even show stable and long‐lasting underwater adhesion. Hence, the synthesized poly(TA‐PA)s, which have high water resistance, are suitable for use as sealing materials in various applications, thus highlighting the applicability of supramolecular polymer materials in underwater surface coatings and adhesion.

Catalytic hydrogenolysis of end-of-life polyolefins can produce value-added liquid fuels and therefore holds great promises in plastic waste reuse and environmental remediation. The major challenge limiting the recycling economic benefit is the severe methanation (usually >20%) induced by terminal C–C cleavage and fragmentation in polyolefin chains. Here, we overcome this challenge by demonstrating that Ru single-atom catalyst can effectively suppress methanation by inhibiting terminal C–C cleavage and preventing chain fragmentation that typically occurs on multi-Ru sites. The Ru single-atom catalyst supported on CeO2 shows an ultralow CH4 yield of 2.2% and a liquid fuel yield of over 94.5% with a production rate of 314.93 gfuels gRu−1 h−1 at 250 °C for 6 h. Such remarkable catalytic activity and selectivity of Ru single-atom catalyst in polyolefin hydrogenolysis offer immense opportunities for plastic upcycling.

As a manned spacecraft operating in orbit for a long time, a space station embodies a country’s scientific and technological strength comprehensively. Building a space station is the final target of the 3-step strategy of China’s manned space program. This paper introduces the design of the Tiangong space station in terms of its design principles, overall scheme, building process, and special system design. On this basis, the paper analyzes and summarizes the technical characteristics of the Tiangong space station in the aspects of system design and optimization, the large proportion of new technologies, the excellent cost-effectiveness ratio, and the high safety and efficiency of the crew’s residence. Finally, it discusses the future application and development of the Tiangong space station.

Long noncoding RNAs (lncRNAs) play crucial roles in melanoma initiation and development, serving as potential therapeutic targets and prognostic markers for melanoma. lncRNA survival-associated mitochondrial melanoma-specific oncogenic noncoding RNA (SAMMSON) is upregulated in many types of human cancers. However, the functions of SAMMSON in melanoma have not been fully elucidated. This study is aimed at investigating the expression and functions of SAMMSON in melanoma development. Bioinformatics analysis was performed to determine the expression of SAMMSON and its correlation with the 10-year overall survival (OS) in melanoma patients. Cell proliferation, migration, invasion, and tumorigenesis were detected by MTT, colony formation, Transwell assays, and mouse xenograft model. The expression of cell cycle-related factors, epithelial-to-mesenchymal transition (EMT) makers, and matrix metalloproteinases (MMPs) was assessed by RT-qPCR and western blotting analysis. The results demonstrated that SAMMSON expression was upregulated in melanoma tissues and cells, and lower SAMMSON expression was correlated with longer 10-year OS. SAMMSON knockdown decreased the proliferation, migration, and invasion of melanoma cells by regulating the expression of proliferation-related genes, EMT factors, and MMPs, respectively. Additionally, Forkhead box protein A2 (FOXA2) was confirmed to be a target of SAMMSON, and the biological effects induced by FOXA2 overexpression were similar to those induced by SAMMSON silencing in melanoma cells. Further studies showed that SAMMSON downregulated FOXA2 expression in melanoma cells by modulating the EZH2/H3K27me3 axis. Taken together, our data indicate that SAMMSON plays an important role in melanoma progression and can be a valuable biomarker and therapeutic target in melanoma.

IntroductionIn China and other Asian nations, Geum japonicum (GJ) is used as functional vegetables or as a type of folk medicine. Ellagic acid (EA) is one of the main active ingredients in GJ and has been utilized in food, cosmetics, and medicinal goods worldwide. Natural deep eutectic solvents (NADESs) have gradually replaced organic solvents for efficient extraction of plant-derived active compounds due to its environmental protection, low toxicity, low solubility, reusability, etc.MethodsNADES with the highest EA yield was selected and the extraction conditions were optimized by response surface methodology (RSM), the antioxidant activity of NADES extract was determined, and finally Fourier transform infrared (FT-IR) and scanning electron microscopy (SEM) were used to explain the mechanism for the increase of EA yield in GJ.ResultsIn this work, several NADESs were tailored for the ultrasound assisted extraction (UAE) of EA from GJ, among which choline chloride-oxalic acid (ChCl:Oa) was the most effective. In optimal conditions, ChCl:Oa extract produced higher EA yields than common organic solvents including methanol, ethanol, and acetone. In vitro antioxidant experiments showed that ChCl:Oa extract had stronger DPPH radical scavenging ability than other solvent extracts. Mechanically, FT-IR results indicated that ChCl:Oa could form a hydrogen bonding with EA, which enhanced the stability of EA. Meanwhile, ChCl:Oa-UAE treatment could destroy the tissue structure of GJ, thereby improving EA yield.DiscussionIn conclusion, these results imply that the ChCl:Oa-UAE method might be an environmentally friendly approach for extracting EA from GJ.

Abstract For now, Alzheimer’s disease (AD) is incurable. But if it can be diagnosed early, the correct treatment can be used to delay the disease. Most of the existing research methods use single or multi-modal imaging features for prediction, relatively few studies combine brain imaging with genetic features for disease diagnosis. In order to accurately identify AD, healthy control (HC) and the two stages of mild cognitive impairment (MCI: early MCI, late MCI) combined with brain imaging and genetic characteristics, we proposed an integrated Fisher score and multi-modal multi-task feature selection research method. We learned first genetic features with Fisher score to perform dimensionality reduction in order to solve the problem of the large difference between the feature scales of genetic and brain imaging. Then we learned the potential related features of brain imaging and genetic data, and multiplied the selected features with the learned weight coefficients. Through the feature selection program, five imaging and five genetic features were selected to achieve an average classification accuracy of 98% for HC and AD, 82% for HC and EMCI, 86% for HC and LMCI, 80% for EMCI and LMCI, 88% for EMCI and AD, and 72% for LMCI and AD. Compared with only using imaging features, the classification accuracy has been improved to a certain extent, and a set of interrelated features of brain imaging phenotypes and genetic factors were selected.

Abstract Background Whether smoking modifies the associations of diabetes and risk factor management with subsequent risk of cardiovascular disease (CVD), and whether the smoking related CVD risk differs among people with and without diabetes are unclear. This study aimed to examine the associations and interactions of smoking, diabetes, and risk factor management in relation to incident CVD. Methods This nationwide, population-based, prospective cohort study of 20 communities from various geographic regions recruited adults aged 40 years or older during 2011–2012. The follow-up survey was conducted between 2014 and 2016. This study included 126,181 participants who were free from CVD at baseline. Results Study participants included 19,397 current smokers (15.4%), 6,049 former smokers (4.8%), and 100,735 never smokers (79.8%). Mean (SD) age ranged from 55.8 (8.6) years to 60.7 (9.1) years. Compared with never smokers, heavy smokers exhibited a greater risk of CVD events among participants with diabetes (multivariable-adjusted hazard ratio [HR], 1.45; 95% CI, 1.17–1.78) than among participants without diabetes (HR, 1.20; 95% CI, 1.01–1.42; P for interaction = 0.006). Compared with participants without diabetes, participants with diabetes who were never smokers and had 5 or more controlled risk factors showed no significantly excess CVD risk (HR, 0.93; 95% CI, 0.71–1.22), but the cardiovascular benefits from risk factor management were counteracted among participants with diabetes who were current smokers (HR, 1.28; 95% CI, 0.77–2.14) or former smokers (HR, 1.22; 95% CI, 0.66–2.28). Conclusions Smoking and diabetes interacted with each other in relation to increased risk of CVD events, and the beneficial effect of risk factor management on CVD risk among participants with diabetes was attenuated by current or former smoking.

This paper proposes a modified model predictive control method with the virtual model (VM-MPC) to generate a virtual reference of the position loop. The dynamic deviation is introduced into the virtual reference as a position advance. Applying this virtual reference as the input of position controllers, the dynamic response is greatly improved without changing the gain of position controllers. Therefore, both the dynamic response and robustness of the position loop are improved when the response delay of the speed loop is uncertain. In order to reduce the influence of model mismatch on model predictive control, instead of the actual feedback, a virtual model feedback of the expected position response is used. With this approach, control parameters of VM-MPC are optimized offline to obtain the fast position response without overshoot. A model compensator is proposed to reduce the mismatch between the virtual model and the real system. The effectiveness and feasibility of the proposed method are verified by simulation and experiment results.

Based on proposed joint human connectome project multi-modal parcellation (JHCPMMP), the study on the binary classification of Alzheimer’s disease was conducted. We tried to build a novel classification model, which can be interpretative and have the ability to deal with the complexity and individual differences of brain networks. The subclass weighted logistic regression (SWLR) based on logistic regression was proposed in this paper. We conducted five groups of experiments, in which the accuracy of HC vs. AD was 95.8%, HC vs. EMCI was 91.6%, HC vs. LMCI was 93.7%, EMCI vs. LMCI was 89.5%, and LMCI vs. AD was 91.6%. In addition, we conducted a follow-up analysis of the coefficient matrix and found that the distribution of core deterioration brain regions in different stages is different in the development of Alzheimer’s disease. We located these brain regions in two-dimensional images and found that they generally show a trend of continuous counterclockwise migration.

The electrocatalytic conversion of biomass into high-value-added chemicals is one of the effective methods of green chemistry. Conventional metal catalysts have disadvantages, such as low atomic utilization and small surface areas. Catalyst materials derived from metal–organic frameworks (MOFs) have received much attention due to their unique physicochemical properties. Here, an MOF-derived non-precious metal CoxNiyS electrocatalyst was applied to the oxidation of biomass-derivative 5-hydroxymethylfurfural (HMF). The HMF oxidation reaction activities were modulated by regulating the content of Co and Ni bimetals, showing a volcano curve with an increasing proportion of Co. When the Co:Ni ratio was 2:1, the HMF conversion rate reached 84.5%, and the yield of the main product, 2,5-furandicarboxylic acid (FDCA), was 54%. The XPS results showed that the presence of high-valent nickel species after electrolysis, which further proved the existence and reactivity of NiOOH, as well as the synergistic effect of Co and Ni promoted the conversion of HMF. Increasing the content of Ni could increase the activity of HMF electrochemical oxidation, and increasing the content of Co could reduce the increase in the anodic current. This study has important significance for designing better HMF electrochemical catalysts in the future.

The spatial distribution pattern of urban spatial structure affects air flow and local meteorological conditions, which in turn influence the diffusion of air pollutants. This study built the urban spatial structure index system based on DEM, urban road networks, and big data. The ordinary kriging interpolation method was used to analyze the spatial distribution of gaseous pollutant concentrations in Jinan City. Correlation analysis, stepwise regression analysis, and bivariate global spatial autocorrelation analysis were used to study the influence of the urban spatial structure index on the spatial distribution of gaseous pollutant concentration. The main conclusions were as follows: (1) Evident spatial and temporal differences were observed in the concentration distribution of gaseous pollutants in Jinan. The spatial distribution of NO2 and CO concentrations showed a gradual decrease from north to south. Spatial heterogeneity was observed in the distribution of SO2 and O3 concentrations. (2) The urban spatial structure indicators had varying effects on the spatial distribution of different gaseous pollutant concentrations. The important factors that influenced the spatial distribution of urban gaseous pollutant concentrations included terrain elevation, building density, building volume, and floor area ratio. The greater the terrain undulation, the denser the building distribution, the greater the difference in building volume, and the greater the plot ratio, the greater the impact on the diffusion and spatial distribution of urban gaseous pollutants. (3) The spatial distribution of urban gaseous pollutant concentrations was significantly affected by the urban spatial structure indicators in the surrounding areas. Furthermore, the spatial distributions of NO2, SO2, CO, and O3 concentrations had a significant negative spatial correlation with the average DEM and standard deviation of the surrounding adjacent areas and a significant positive spatial correlation with the average and standard deviation of building height, standard deviation of building area, and building density in the surrounding adjacent areas (in June).

Abstract Background Irisin is a novel myokine associated with obesity, which is a traditional cardiovascular risk factor (CVRF). The present study aimed to investigate the association between serum irisin and a single CVRF as well as the clustering of CVRFs among Chinese overweight/obese population. Methods A total of 98 overweight and 93 obese subjects without clinical treatments were enrolled in this study. Subjects were then divided into two groups, based on the serum irisin level: a low irisin group (1.10–13.44 ng/ml) and a high irisin group (13.49–29.9 ng/ml). The clustering of CVRFs, smoking, diabetes mellitus, dyslipidemia and hypertension, was classified as 0, 1, 2 and ≥ 3 CVRFs. The demographic and baseline clinical characteristics of all participants were collected and serum irisin was measured. Results The high serum irisin group had significantly higher high-density lipoprotein cholesterol but lower fasting plasma glucose than the low serum irisin group. Additionally, the high serum irisin group had a significantly lower prevalence of smoking, diabetes mellitus and dyslipidemia than the low serum irisin group. Increased serum irisin was significantly associated with a reduced risk of smoking and dyslipidemia in both the unadjusted and adjusted models. Furthermore, high serum irisin significantly reduced the risk of the prevalence of 1, 2 and ≥ 3 CVRFs. Conclusions among the Chinese overweight/obese populations, high serum irisin is negatively associated with smoking, dyslipidemia and the clustering of CVRFs. Thus, high serum irisin is potentially associated with a low risk of cardiovascular diseases in the Chinese overweight/obese population.

Background: There is an increasing trend of Metabolic syndrome (MetS) prevalence, which has been considered as an important contributor for cardiovascular disease (CVD), cancers and diabetes. However, there is often a long asymptomatic phase of MetS, resulting in not diagnosed and intervened so timely as needed. It would be very helpful to explore tools to predict the probability of suffering from MetS in daily life or routinely clinical practice. Objective: To develop models that predict individuals’ probability of suffering from MetS timely with high efficacy in general population. Methods: The present study enrolled 8964 individuals aged 40–75 years without severe diseases, which was a part of the REACTION study from October 2011 to February 2012. We developed three prediction models for different scenarios in hospital (Model 1, 2) or at home (Model 3) based on LightGBM (LGBM) technique and corresponding logistic regression (LR) models were also constructed for comparison. Model 1 included variables of laboratory tests, lifestyles and anthropometric measurements while model 2 was built with components of MetS excluded based on model 1, and model 3 was constructed with blood biochemical indexes removed based on model 2. Additionally, we also investigated the strength of association between the predictive factors and MetS, as well as that between the predictors and each component of MetS. Results: In this study, 2714 (30.3%) participants suffer from MetS accordingly. The performances of the LGBM models in predicting the probability of suffering from MetS produced good results and were presented as follows: model 1 had an area under the curve (AUC) value of 0.993 while model 2 indicated an AUC value of 0.885. Model 3 had an AUC value of 0.859, which is close to that of model 2. The AUC values of LR model 1 and 2 for the scenario in hospital and model 3 at home were 0.938, 0.839 and 0.820 respectively, which seemed lower than that of their corresponding machine learning models, respectively. In both LGBM and logistic models, gender, height and resting pulse rate (RPR) were predictors for MetS. Women had higher risk of MetS than men (OR 8.84, CI: 6.70–11.66), and each 1-cm increase in height indicated 3.8% higher risk of suffering from MetS in people over 58 years, whereas each 1- Beat Per Minute (bpm) increase in RPR showed 1.0% higher risk in individuals younger than 62 years. Conclusion: The present study showed that the prediction models developed by machine learning demonstrated effective in evaluating the probability of suffering from MetS, and presented prominent predicting efficacies and accuracies. Additionally, we found that women showed a higher risk of MetS than men, and height in individuals over 58 years was important factor in predicting the probability of suffering from MetS while RPR was of vital importance in people aged 40–62 years.

BackgroundOpportunely screening for diabetes is crucial to reduce its related morbidity, mortality, and socioeconomic burden. Machine learning (ML) has excellent capability to maximize predictive accuracy. We aim to develop ML-augmented models for diabetes screening in community and primary care settings.Methods8425 participants were involved from a population-based study in Hubei, China since 2011. The dataset was split into a development set and a testing set. Seven different ML algorithms were compared to generate predictive models. Non-laboratory features were employed in the ML model for community settings, and laboratory test features were further introduced in the ML+lab models for primary care. The area under the receiver operating characteristic curve (AUC), area under the precision-recall curve (auPR), and the average detection costs per participant of these models were compared with their counterparts based on the New China Diabetes Risk Score (NCDRS) currently recommended for diabetes screening.ResultsThe AUC and auPR of the ML model were 0·697and 0·303 in the testing set, seemingly outperforming those of NCDRS by 10·99% and 64·67%, respectively. The average detection cost of the ML model was 12·81% lower than that of NCDRS with the same sensitivity (0·72). Moreover, the average detection cost of the ML+FPG model is the lowest among the ML+lab models and less than that of the ML model and NCDRS+FPG model.ConclusionThe ML model and the ML+FPG model achieved higher predictive accuracy and lower detection costs than their counterpart based on NCDRS. Thus, the ML-augmented algorithm is potential to be employed for diabetes screening in community and primary care settings.

PurposeThe aim of this study was to assess the safety and efficacy of microwave ablation combined with apatinib [vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor] and camrelizumab [anti-programmed death-1 (PD-1) antibody] in patients with advanced hepatocellular carcinoma (HCC).Patients and methodsPatients (age, >18 years) with histologically confirmed HCC and refractory to at least the standard first-line therapy were enrolled from 2 September 2018 to 17 January 2022. They first received ultrasound-guided subtotal microwave ablation. Then, beginning at 7–14 days after ablation, they were given apatinib (250 mg once daily) and camrelizumab (200 mg once every 2 weeks) until unacceptable toxicity or disease progression or death. The coprimary end points were progression-free survival (PFS) and overall survival (OS).ResultsFourteen HCC patients with Barcelona Clinic of Liver Cancer (BCLC) B and C stages were retrospectively enrolled. At data cutoff, follow-up period ranged from 3.8 to 41.3 months (median, 17.4 months), and the median (95% confidence interval) duration of exposure (DE) was 6.4 (4.0–8.9) months. The PFS and OS were 10.8 (0–23.5) months and 19.3 (2.4–36.2) months, respectively. Three (21.4%) patients achieved a confirmed complete response (CR). Confirmed partial response (PR), stable disease (SD), and progression of disease (PD) were achieved in four (28.6%), four (28.6%), and three (21.4%) patients, respectively. The objective response rate (ORR) and disease control rate (DCR) were 50.0% (20.0%-80.0%) and 78.6% (54.0%-100%), respectively. The serious treatment-related adverse events included one (7.1%) case with reactive capillary hemangiomas (grade 4), one (7.1%) with hypertension (grade 3), two (14.3%) with elevated transaminase and bilirubin (grade 4), one (7.1%) with platelet count decrease (grade 4), one (7.1%) with hepatic failure (grade 4), and two (14.3%) with gastrointestinal bleeding (grades 3 and 4).ConclusionsMicrowave ablation combined with apatinib and camrelizumab treatment in advanced HCC patients demonstrated intriguing clinical activity and resulted in durable antitumor responses and significantly improved PFS and OS. The combination therapy is well tolerated, enabling further clinical studies.

Lung cancer is the malignant tumor with high invasion and metastasis, which seriously threatens public health. Previous study showed that NLRP3 could promote the occurrence of lung tumors in B(a)P-induced mice. MicroRNAs are closely related to the progression and metastasis of lung cancer by regulating target genes. However, which miRNAs affect the migration and invasion of lung cancer cells through regulating NLRP3 remains poorly defined. In this study, the miRNAs targeting NLRP3 were selected from TargetScan and miRDB database and finally miR-223-3p was chosen due to the consistent expression in both A549 and H520 cells. Then, the migration and invasion of lung cancer cells were detected with miR-223-3p mimic and inhibitor using Transwell assay, at the same time the expression of NLRP3, cleaved caspase-1, IL-1β and IL-18 was determined using Western Blot and immunohistochemistry assay. Our data demonstrated that miR-223-3p was upregulated in both A549 and H520 cells. Furthermore, the migration and invasion of A549 and H520 cells were promoted after inhibiting miR-223-3p. Besides, the levels of NLRP3, cleaved caspase-1, IL-1β and IL-18 were increased in the two lung cancer cells. And the corresponding results were contrary in miR-223-3p mimic group. Taken together, miR-223-3p attenuates the migration and invasion of NSCLC cells by regulating NLRP3, which provides evidence for the prevention and targeted treatment of NSCLC.

Background Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged

Background Intravenous thrombolysis with alteplase is widely used in patients with acute ischemic stroke presenting early after symptom onset. Recent phase II trials have suggested that intravenous tenecteplase may be safer and associated with higher early reperfusion rates as compared with alteplase. This study investigates whether intravenous tenecteplase is noninferior to intravenous alteplase for the treatment of acute ischemic stroke. Methods This is a pragmatic, registry‐linked, prospective, randomized (1:1) controlled, open‐label parallel group clinical trial (AcT [Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke]) with blinded end point assessment of 1600 patients to test if intravenous tenecteplase (0.25 mg/kg body weight, maximum dose 25 mg) is noninferior to intravenous alteplase (0.9 mg/kg body weight; maximum dose, 90 mg) in patients with acute ischemic stroke eligible for intravenous thrombolysis in clinical routine. Patients are recruited from comprehensive and primary stroke centers and enrolled using deferral of consent. The proposed sample has at least 90% power with a noninferiority margin of 5%, assuming incidence of the 90‐day modified Rankin Scale score of 0 to 1 is 38% in the tenecteplase and 35% in the alteplase groups, and a loss to follow‐up rate

Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is the first enzyme in the de novo purine nucleotide synthesis pathway and is essential for cell development. However, the effect of PRPS1 on melanoma proliferation and metastasis remains unclear. This study aimed to investigate the regulatory mechanism of PRPS1 in the malignant progression of melanoma. Here, we found PRPS1 was upregulated in melanoma and melanoma cells. In addition, our data indicated that PRPS1 could promote the proliferation and migration and invasion of melanoma both in vitro and in vivo. PRPS1 also could inhibit melanoma cell apoptosis. Furthermore, we found NRF2 is an upstream transcription factor of PRPS1 that drive malignant progression of melanoma.

Abstract The information on crustal thickness in Antarctica can provide significant constraints on its crustal deformation and tectonic evolution. To generate reliable images of crustal features, we investigate the model of Moho depth and crustal thickness beneath Antarctica by applying the Bott‐Parker's formulas based on the Gauss‐fast Fourier transform method through a comprehensive analysis of gravity data, ice and sediment thicknesses and bedrock elevation, combined with seismic constraints. Tests with synthetic data indicate that the iterative inversion algorithm can yield a highly accurate Moho topography. Ultimately, inverted crustal thickness reveals a more detailed crustal image by clearly identifying more tectonic elements at different scales than previous results and correlates well with major tectonic provinces. Airy isostasy and flexural isostasy models are used to assess the crustal isostatic compensation. The distinctive negative isostatic anomalies are observed in the Transantarctic Mountains and the East Antarctic areas of the great escarpment in the Dronning Maud Land and Aurora and Wilkes Subglacial Basin, indicating that the low density of the uppermost mantle and lithospheric strength may play important roles in compensating for their elevations. Variations in crustal thickness in interior East Antarctica are analyzed; the thickened crust from Dronning Maud Land to the Gamburtsev Subglacial Mountains may be associated with the collision of continental blocks and is interpreted as the fossil sutures. We compare the relationship between the Moho and Curie interfaces and find that the uppermost mantle is magnetized in some areas of East Antarctica, which may indicate preserved Precambrian cratonic roots.

Single atom catalysts (SACs) are constituted by isolated active metal centers, which are heterogenized on inert supports such as graphene, porous carbon, and amorphous carbon. The thermal stability, electronic properties, and catalytic activities of the metal center can be controlled via manipulating the neighboring heteroatoms such as nitrogen, oxygen, and sulfur. Due to the atomical dispersion of the active catalytic centers, the amount of metal required for catalysis can be decreased. Furthermore, new possibilities are offered to easily control the selectivity of a given transformation process as well as to improve turnover frequencies and turnover numbers of target reactions. Among them, Fe–N–C single atom catalysts own special electronic structure, and have been widely used in many fields of electrocatalysis. This review aims to summarize the synthesis of Fe–N–C based on anchoring individual iron atoms on carbon/graphene. The spin-related properties of Fe–N–C catalysts are described, including the relation between spin and electron structure of Fe–Nx as well as the coupling between electronic structure of Fe–Nx and electronic (orbit) of CO2, N2 and O2. Next, mechanistic investigations conducted to understand the specific behavior of Fe–N–C catalysts are highlighted, including C, N, O electro-reduction. Finally, some issues related to the future developments of Fe–N–C are put forward and corresponding feasible solutions are offered.

Leuprolide acetate microspheres developed by Shanghai Livzon Pharmaceutical Co., Ltd. (T) have been marketed in China for more than 10 years, benefiting a large number of patients, and will continue to play an important role in China. However, as a generic drug, it is unclear whether there is a difference in efficacy between T and the original product Enantone® (R). This study compared the differences in efficacy and safety of two 1-month depot formulations in 48 healthy Chinese male subjects by comparing multiple pharmacokinetic (PK) and pharmacodynamic (PD) parameters. The main research indicators were the PK parameters of leuprolide (Cmax, AUC0-t, AUC0-D7, and AUCD7-t) and the PD parameters of testosterone (Emax, AUEC0-t, AUEC0-D7, and AUECD7-t) after 42 days of administration. The Cmax, AUC0-t, AUC0-D7 and AUCD7-t of leuprolide were slightly higher in the T group than in the R group with 90% confidence intervals (CIs) of 94.43–118.53%, 109.13–141.88%, 109.53–139.54%, and 105.17–145.74%, respectively. No significant differences in the PD parameters (Emax, AUEC0-t, AUEC0-D7, and AUECD7-t) existed between the T and R groups, and 90% CIs were 62.80–93.57%, 88.17–110.55, 95.72%–118.50%, and 79.77–105.63, respectively. At 672 h (D28), the castration rate of T was 91.30% (21/23) and that of R was 60.87% (14/23). The PK characteristics were consistent and the inhibitory effects on testosterone levels were similar in both T and R groups; further, clinical safety was observed for both T and R formulations, suggesting that these two products can replace each other in clinical practice.Clinical Trial Registration:http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml, identifier CTR20200641.

The objective of this study is to explore the effect and mechanism of ultrasound on chitin extraction from shrimp shells powder (SSP) by the co-fermentation of Bacillus subtilis and Acetobacter pasteurianus. After pre-treating the SSP with high-intensity ultrasound (HIU) at 800 W, the protease activity in the fermentation solution reached 96.9 U/mL on day 3, which was significantly higher than for SSP that had not been pre-treated with ultrasound (81.8 U/mL). The fermentation time of the chitin extraction process was 5.0 d without ultrasound pre-treatment, while it was shortened to 4.5 d when using ultrasound at 800 W to treat SSP. However, there were no obvious differences when we applied ultrasound at low power (200 W, 400 W). Furthermore, chitin purified from shrimp shells pre-treated with HIU at 800 W exhibited lower molecular weight (11.2 kDa), higher chitin purity (89.8%), and a higher degree of deacetylation (21.1%) compared to SSP with no ultrasound pre-treatment (13.5 kDa, 86.6%, 18.5%). Results indicate that HIU peels off the protein/CaCO3 matrix that covers the SSP surface. About 9.1% of protein and 4.7% of Ca2+ were released from SSP pre-treated with HIU at 800 W. These figures were both higher than with no ultrasound pre-treatment (4.5%, 3.2%). Additionally, the amount of soluble protein extracted from SSP through HIU at 800 W was 50% higher than for the control sample. SDS-PAGE analysis indicated that the soluble protein was degraded to the micromolecule. It also revealed that HIU (600, 800 W) induced the secondary and tertiary structure destruction of protein extracted from SSP. In conclusion, HIU-induced degradation and structural damage of protein enhances the protein/CaCO3 matrix to be peeled off from SSP. Also, in the co-fermentation process, an increase of protease activity further accelerates deproteinization.

The permanent magnet synchronous motor (PMSM) has been widely used in the field of ship electric propulsion due to its advantages of a small size, light weight, low loss, and high efficiency. In this paper, a 100 kW ship-side thruster motor was taken as the research object, and the problem of the high harmonic content of the air gap magnetic flux density in the motor was addressed by designing a rotor eccentricity. On this basis, the hybrid Taguchi method of genetic algorithm was used to optimize the rotor structural parameters with increasing the efficiency and reducting the cost of the motor as the optimization objectives. The results show that the performance and economy of the motor have been greatly improved after optimization. Finally, the motor weight reduction hole was designed, and a prototype was manufactured and tested. The test data are within the allowable range compared with the simulation data, verifying the effectiveness of the multiobjective optimization algorithm proposed in this paper.

In order to explore the fracture law and structural evolution characteristics of overlying strata in deep high-stress mining, according to the geometric characteristics and mechanical causes of overlying strata in different mining stages of the stope, four stages of overlying strata structure model are established and analyzed in turn. According to the characteristics of the overburden load transfer path in the deep high-stress stope, the fracture law and macroscopic mechanical response of overburden are analyzed by MATLAB and PFC2D numerical simulation method. The evolution model of overburden structure and load transfer in ‘four stages and three modes’ of the deep high-stress stope is constructed, and the stage fracture effect of ‘beam, plate and arch’ is put forward. The results show that the overburden rock is a fixed beam structure before the initial weighting. After the initial weighting, it evolves into a plate structure with three sides fixed and one side simply supported. After the periodic weighting, the overburden rock structure further evolves into a plate structure with one side fixed and three sides simply supported. After full mining, the overburden rock forms an arch structure, and the load is transmitted by the beam–plate–arch path. The findings of the study provide an important basis for exploring the nature of overburden transport and load transfer in deep high-stress quarries and strengthening overburden prevention and control.

Abstract Background As a new type of molecular marker, microRNAs (miRNAs) can be used for early diagnosis and prognosis prediction of malignant tumors, and has broad clinical application prospects. This paper mainly studies the important role of miR-889 in the occurrence and development of hepatocellular carcinoma and the prognostic significance of miR-889 in hepatocellular carcinoma. Methods Quantitative real-time PCR analysis detected the expression levels of miR-889 in hepatocellular carcinoma tissues and cell lines. Kaplan-Meier curve and Cox regression analysis were used to explore the prognostic significance of miR-889 in hepatocellular carcinoma. The CCK-8 and Transwell assays assay were used to assess cell proliferation, migration, and invasion abilities ability. Results The expression of miR-889 in hepatocellular carcinoma tissues was significantly higher than that in adjacent tissues. Overexpression of miR-889 was significantly associated with TNM stage, hepatitis B virus infection, and cirrhosis. Patients with high miR-889 expression had shorter overall survival than those with low miR-889 expression. And functional studies in two hepatocellular carcinoma cell lines have shown that overexpression of miR-889 significantly promoted cell proliferation, migration, and invasion in vitro. Conclusions Overall, miR-889 was upregulated in hepatocellular carcinoma tissues and cell lines, and overexpression of miR-889 promoted cell proliferation, migration, and invasion in hepatocellular carcinoma cells. Based on our findings, high expression of miR-889 may promote the progression of hepatocellular carcinoma, and high expression of miR-889 is also forecasted for an unfavorable prognosis in hepatocellular carcinoma.

Abstract Background Despite recent advances in diagnostic and therapeutic approaches for gastric cancer (GC), the survival of patients with advanced GC remains very low. Islet-1 (ISL1) is a LIM-homeodomain transcription factor, which is upregulated and promotes cell proliferation in GC. The exact mechanism by which ISL1 influences GC development is unclear. Methods Co-immunoprecipitation (co-IP) and glutathione S-transferase (GST)-pulldown assays were employed to evaluate the interaction of ISL1 with CDK1. Western blot and immunohistochemistry analyses were performed to evaluate the ability of CDK1 to phosphorylate ISL1 at Ser 269 in GC cell and tissue specimens. Chromatin immunoprecipitation (ChIP), ChIP re-IP, luciferase reporter, and CCK-8 assays were combined with flow cytometry cell cycle analysis to detect the transactivation potency of ISL1-S269-p and its ability to promote cell proliferation. The self-stability and interaction with CDK1 of ISL1-S269-p were also determined. Results ISL1 is phosphorylated by CDK1 at serine 269 (S269) in vivo. Phosphorylation of ISL1 by CDK1 on serine 269 strengthened its binding on the cyclin B1 and cyclin B2 promoters and increased its transcriptional activity in GC. Furthermore, CDK1-dependent phosphorylation of ISL1 correlated positively with ISL1 protein self-stability in NIH3T3 cells. Conclusions ISL1-S269-p increased ISL1 transcriptional activity and self-stability while binding to the cyclinB1 and cyclinB2 promoters promotes cell proliferation. ISL1-S269-p is therefore crucial for tumorigenesis and potentially a direct therapeutic target for GC.

Abstract Generalized auto-calibrating partially parallel acquisitions (GRAPPA) and other parallel Magnetic Resonance Imaging (pMRI) methods restore the unacquired data in k-space by linearly calculating the undersampled data around the missing points. In order to obtain the weight of the linear calculation, a small number of auto-calibration signal (ACS) lines need to be sampled at the center of the k-space. Therefore, the sampling pattern used in this type of method is to full sample data in the middle area and undersample in the outer k-space with nominal reduction factors. In this paper, we propose a novel reconstruction method with a multiple variable density sampling (MVDS) that is different from traditional sampling patterns. Our method can significantly improve the image quality using multiple reduction factors with fewer ACS lines. Specifically, the traditional sampling pattern only uses a single reduction factor to uniformly undersample data in the region outside the ACS, but we use multiple reduction factors. When sampling the k-space data, we keep the ACS lines unchanged, use a smaller reduction factor for undersampling data near the ACS lines and a larger reduction factor for the outermost part of k-space. The error is lower after reconstruction of this region by undersampled data with a smaller reduction factor. The experimental results show that with the same amount of data sampled, using NL-GRAPPA to reconstruct the k-space data sampled by our method can result in lower noise and fewer artifacts than traditional methods. In particular, our method is extremely effective when the number of ACS lines is small.

Chalkiness, which is highly affected by nitrogen (N) management during grain filling, is critical in determining rice appearance quality and consumer acceptability. We investigated the effects of N application rates 75 (N1), 150 (N2), and 225 (N3) kg ha−1 on the source-sink carbohydrate accumulation and grain filling characteristics of two indica hybrid rice cultivars with different chalkiness levels in 2019 and 2020. We further explored the relationship between grain filling and formation of chalkiness in superior and inferior grains. In this study, carbohydrates in the functional leaves and grains of the two varieties, and grain filling parameters, could explain 66.2%, 68.0%, 88.7%, and 91.6% of the total variation of total chalky grain rate and whole chalkiness degree, respectively. They were primarily concentrated in the inferior grains. As the N fertilizer application rate increased, the chalky grain rate and chalkiness degree of both the superior and inferior grains decreased significantly. This interfered with the increase in total chalky grain rate and chalkiness. Moreover, the carbohydrate content in the functional leaves increased significantly in N2 and N3 compared with that in N1. The transfer of soluble sugar from the leaves to the grains decreased the soluble sugar and increased total starch contents, accelerated the development of grain length and width, increased grain water content, and effectively alleviated the contradiction between source and sink. These changes promoted the carbohydrate partition in superior and inferior grains, improved their average filling rate in the middle and later stages, optimized the uniformity of inferior grain fillings, and finally led to the overall reduction in rice chalkiness.

BackgroundThe status of circulating tumor cells (CTCs) is related to the recurrence of hepatocellular carcinoma (HCC), which is also one of the reasons for the poor prognosis of HCC. The purpose of this study was to explore whether CTCs can help guide the choice of treatment methods for HCC.MethodsThis study is a multicenter retrospective study, including 602 patients with HCC. CTCs were detected in the overall cohort before operation. There were 361 patients in the training cohort and 241 patients in the validation cohort. Patients were divided into CTC-negative group (CTCs = 0/5 mL) and the CTC-positive group (CTCs ≥ 1/5 mL) according to CTCs status. Subgroup analysis was performed according to CTCs status. We compared overall survival, and recurrence outcomes for HCC patients with different CTC statuses after undergoing radiofrequency ablation (RFA) or surgical resection (SR)ResultsThere was no significant difference in overall survival (OS) and recurrence-free survival (RFS) between the RFA group and SR group for CTC-negative patients in both the training cohort and the validation cohort (P > 0.05). However, among CTC-positive patients, the clinical outcome of patients in the SR group was significantly better than those in the RFA group. CTC-positive patients who underwent RFA had increased early recurrence compared to those who underwent SR. RFA is an independent risk factor for survival and recurrence in CTC-positive HCC patientsConclusionsThe CTC status could serve as an indicator to guide the choice between surgical resection or radiofrequency ablation for early hepatocellular carcinoma. Surgical resection is recommended for CTC-positive patients.

Regulation of chromatin structure and accessibility determines the transcription activities of genes, which endows the host with function-specific patterns of gene expression. Upon viral infection, the innate immune responses provide the first line of defense, allowing rapid production of variegated antiviral cytokines. Knowledge on how chromatin accessibility is regulated during host defense against viral infection remains limited. Our previous work found that the nuclear matrix protein SAFA surveilled viral RNA and regulated antiviral immune genes expression. However, how SAFA regulates the specific induction of antiviral immune genes remains unknown. Here, through integration of RNA-seq, ATAC-seq and ChIP-seq assays, we found that the depletion of SAFA specifically decreased the chromatin accessibility, activation and expression of virus induced genes. And mutation assays suggested that the RNA-binding ability of SAFA was essential for its function in regulating antiviral chromatin accessibility. RIP-seq results showed that SAFA exclusively bound with antiviral related RNAs following viral infection. Further, we combined the CRISPR-Cas13d mediated RNA knockdown system with ATAC-qPCR, and demonstrated that the binding between SAFA and according antiviral RNAs specifically mediated the openness of the corresponding chromatin and following robust transcription of antiviral genes. Moreover, knockdown of these associated RNAs dampened the accessibility of related genes in an extranuclear signaling pathway dependent manner. Interestingly, VSV infection cleaved SAFA protein at the C-terminus which deprived its RNA binding ability for immune evasion. Thus, our results demonstrated that SAFA and the interacting RNA products collaborated and remodeled chromatin accessibility to facilitate antiviral innate immune responses.

Damage-associated molecular patterns (DAMPs) are the primary promoter of progressive neuroinflammation and are associated with chronic stress-related emotional disorders. The present study investigated the role and mechanism of extracellular nucleosomes and histones, the newly defined DAMPs, in mice with chronic stress. C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) and corticosterone drinking, respectively, for 4 weeks. Negative emotional behaviors were comprehensively investigated. Microglial morphology, oxidative stress, and inflammation, as well as C-type lectin receptor 2D (Clec2d) and Toll-like receptor 9 (TLR9) expression in medial prefrontal cortex (mPFC) were assessed with flow cytometer and cell sorting. Specifically, microglial pro-inflammatory activation and inflammation were further investigated with stereotactic injection of recombinant nucleosomes and histones in mPFC and further evaluated with AAV-Clec2d knocking-down, DNase I, and activated protein C (APC) pretreatment. Moreover, the rescue effect by AAV-Clec2d knocking-down was observed in mice with chronic stress. Mice with chronic stress were presented as obviously depressive- and anxiety-like behaviors and accompanied with significant microglial oxidative stress and inflammation, indicating by reactive oxygen species (ROS) production, primed nuclear factor-κB (NF-κB) signaling pathway, activated NACHT, LRR, and PYD domain–containing protein 3 (NLRP3) inflammasome, and upregulated Clec2d and TLR9 in mPFC, together with histones dictation in cerebrospinal fluid and extracellular trap formation. Stereotactic injection of nucleosomes was contributed to promote microglial inflammation rather than histones in mPFC, indicating that the pro-inflammatory role was derived from extracellular histones-bound DNA but not freely histones. AAV-Clec2d knocking-down, DNase I, and APC were all effective to inhibit nucleosome-induced microglial oxidative stress and inflammation. Moreover, AAV-Clec2d knocking-down in mice with chronic stress exhibited reduced microglial inflammation and improved negative emotional behaviors. Our findings reveal a novel mechanism of DAMP-associated inflammation that extracellular nucleosomes accelerate microglial inflammation via Clec2d and TLR9, and then contribute to chronic stress-induced emotional disorders.