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The standard k–ε model coupled with the mixture model was used to study two-phase flow in a large dissolved air flotation (DAF) unit. The numerical results can simulate fairly well the velocity vectors and air volume fraction distribution data of a DAF unit from the literature. The typical DAF structure parameters were analyzed in detail to investigate their predicted influences on the internal flow structure and removal effect. The simulations indicated that the short length of the separation zone was not conducive to the formation of a stratified flow pattern, and the turbulent kinetic energy at the bottom of the separation zone increased as the length decreased. With the increase in the height of the DAF tank, the horizontal flow structure in the separation zone would be disrupted, and the distribution range and the intensity of the turbulence kinetic energy increased. Further analysis showed that the formation of horizontal stratified flow facilitated the removal of bubbles, and the formation of stratified flow is related to the size of the DAF unit. Detailed analyses showed that the reduction of DAF height and the increase of separation zone length were beneficial to improve the bubble removal efficiency. Finally, a theoretical analysis was carried out to study the relationship between DAF parameters and the removal effect. The results revealed that when the horizontal flow structure was not destroyed and stratified flow occurred, the bubble removal efficiency was positively linearly related to the length of the separation zone. The removal efficiency increases as DAF height decreases. HIGHLIGHTS The formation of horizontal stratified flow facilitated the removal of bubbles.; The stratified flow would be formed under the condition of appropriate structure parameters.; When the horizontal flow structure was not destroyed and stratified flow occurred, the bubble removal efficiency was positively linearly related to the length of the separation zone. And it changed in the opposite pattern when the DAF height varied.;

Cu-SSZ-13 zeolites are highly active for standard NH3-SCR, but their activity is unexpectedly inhibited in the presence of NO2. This work demonstrates that strong oxidation by NO2 forces Cu ions to exist mainly as CuII species with low mobility, which is responsible for this distinctive behavior.

The Berezinskii-Kosterlitz-Thouless topological phase transition has been observed in various systems, and involves vortex-antivortex pairs binding/un-binding. Here, such a transition is observed in a 2D ferromagnetic quantum anomalous Hall insulator film, revealed by temperature-dependent magneto-electrical transport measurements.

Abstract In this paper, a real cloud computing platform-oriented Low-rate Denial of Service (LDoS) attack detection method based on time-frequency characteristics of traffic data is proposed. All the traffic data flowing through the Web server is acquired by the collection and storage system, the original traffic data is divided into multiple flow segments by the preprocessing module, and the simple statistical features of several data packets in the flow are extracted by the analysis tool to form the detection sequence. The deep neural network is used to learn the potential time-frequency domain connection in the normal feature sequence and generate the reconstructed sequence. The discrimination module discriminates against the LDoS attack according to the difference between the reconstructed sequence and the input data in the time-frequency domain. The experimental results show that the proposed method can accurately detect the attack features in the stream segments in a very short time, and can achieve high detection accuracy for complex and diverse LDoS attacks. Because only the statistical characteristics of data packets are used, it is not necessary to analyze the data in the packets, which can be adapted to different network environments.

In this paper, the gel properties of sodium alginate with Y3+, Ce3+, La3+ and Er3+ were studied. By studying the mechanical properties, equilibrium water content, ion exchange rate and gel mechanism of seaweed rare earth gel, it was found that: The coordination form of rare earth ions and carboxyl group in sodium alginate was pseudo-bridged monodentate coordination and bridge coordination. At the same time, the special three-dimensional network structure of the rare earth gel was formed through the planar and non-planar geometry formed by intramolecular and intermolecular chelation, and the gel strength of the gel formed by La3+, Y3 +, Er3+, Ce3+ and sodium alginate M/G≈1 was between 32 and 41 N, the Young’s modulus was between 14 and 20 N, the elasticity was between 55% and 59%, the equilibrium water content was greater than 93%, the strength of the four gel was Ce3+> Er3+> Y3+> La3+, the elasticity was Ce3+1, the affinity of seaweed rare earth gel was in this order：Er3+>Ce3+>Y3+>La3+. When M/G=0.99≈1 and M/G=0.19 Er3+> Y3+> La3+. Among them, Ce3+, Y3+ and La3+ had a certain preference for G fragment of sodium alginate, and Er3+ had a certain preference for M fragment. This study would lay a theoretical foundation for the intensive processing and utilization of sodium alginate and the development of new functional materials of rare earth elements.

Abstract Soft, worm-like robots show promise in complex and constrained environments due to their robust, yet simple movement patterns. Although many such robots have been developed, they either rely on tethered power supplies and complex designs or cannot move external loads. To address these issues, we here introduce a novel, maggot-inspired, magnetically driven “mag-bot” that utilizes shape memory alloy-induced, thermoresponsive actuation and surface pattern-induced anisotropic friction to achieve locomotion inspired by fly larvae. This simple, untethered design can carry cargo that weighs up to three times its own weight with only a 17% reduction in speed over unloaded conditions thereby demonstrating, for the first time, how soft, untethered robots may be used to carry loads in controlled environments. Given their small scale and low cost, we expect that these mag-bots may be used in remote, confined spaces for small objects handling or as components in more complex designs.

Nanoscale porous building blocks hold great promise for a range of thermal management technologies but often porous nanoparticle assemblies are intrinsically brittle. Here, the authors report 3D printing of porous silica voxels with polymeric additives to enable the coupling between additive manufacturing and hierarchical assembly for superior machinability and structural controllability.

Thyroid-associated ophthalmopathy(TAO)is an organ-specific autoimmune disease, which will cause a series of symptoms to significantly reduce the health level and life quality of patients. The pathogenesis of TAO has not been fully clarified. At present, there is a lack of unified and mature treatment scheme of it. Indeed, T-helper 17 lymphocyte(Th17)cells, regulatory T(Treg)cells and their imbalance are closely related to the immunological pathogenesis of TAO. It is currently believed that the cytokines secreted by Th17 cells can not only promote the inflammatory response of TAO and the fibrosis of orbital connective tissue, but also inhibit the adipogenic differentiation of TAO orbital connective tissue. In addition, Treg cells mainly exert immunosuppressive effect on TAO and delay the disease progression. At the same time, there is a dynamic balance relationship between Th17 and Treg cells, the imbalance of Th17/Treg cells can trigger the occurrence and development of TAO. This paper mainly expounds the influence mechanism of Th17, Treg cells and their balance on TAO, and analyzes the reasons for the differences between different research results, so as to provide some reference for the study of the pathogenesis and clinical treatment of TAO.

BTB and CNC homologous (BACH) proteins, including BACH1 and BACH2, are transcription factors that are widely expressed in human tissues. BACH proteins form heterodimers with small musculoaponeurotic fibrosarcoma (MAF) proteins to suppress the transcription of target genes. Furthermore, BACH1 promotes the transcription of target genes. BACH proteins regulate physiological processes, such as the differentiation of B cells and T cells, mitochondrial function, and heme homeostasis as well as pathogenesis related to inflammation, oxidative-stress damage caused by drugs, toxicants, or infections; autoimmunity disorders; and cancer angiogenesis, epithelial-mesenchymal transition, chemotherapy resistance, progression, and metabolism. In this review, we discuss the function of BACH proteins in the digestive system, including the liver, gallbladder, esophagus, stomach, small and large intestines, and pancreas. BACH proteins directly target genes or indirectly regulate downstream molecules to promote or inhibit biological phenomena such as inflammation, tumor angiogenesis, and epithelial-mesenchymal transition. BACH proteins are also regulated by proteins, miRNAs, LncRNAs, labile iron, and positive and negative feedback. Additionally, we summarize a list of regulators targeting these proteins. Our review provides a reference for future studies on targeted drugs in digestive diseases.

BackgroundAlzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive progress and memory loss, which eventually develops into dementia. It can cause personality disorders and decreased quality of life of patients. Currently, AD patients account for 60–70% of global dementia patients and the incidence rate of AD is increasing annually. AD not only causes pain to patients but also brings a heavy burden to the entire family. Studies have found that there is a connection between mitochondrial dysfunction and other biochemical changes in AD like classical neuropathological hallmarks (β-amyloid and tau protein), inflammation pathways, oxidative stress, and so on. Evidence shows that early treatment targeted directly to mitochondria could extend the lifespan of model mice and decrease the relevant neuropathological markers. Therefore, research on the mitochondrial dysfunction of AD can be of potential significance for clinical treatment. To date, few bibliometric analysis articles related to mitochondrial dysfunction of AD have been published. Bibliometric analysis refers to quantitatively analyzing certain aspects of articles like publishers, authors, and countries by using statistical and mathematical methods. Combined with statistical software, a large number of papers can be converted to visualization figures and tables, which provide vital information such as keyword hotspots and the names of contributing authors. Through the bibliometric analysis method, our study aimed to provide study trends and keyword hotpots for researchers to conduct further relevant research in this field.MethodsWe used the Web of Science core collection database as a literature retrieval tool to obtain data related to mitochondrial changes in Alzheimer’s disease during the last 20 years. The retrieval type was [TS = (Alzheimer’s disease)] ND [TS = (mitochondrion)], ranging from January 1, 2000 to June 30, 2022. VOSviewer v1.6.18, Arcgis 10.8, and HistCite pro 2.1 were used to conduct data visualization analysis. VOSviewer v1.6.18 made relevant network visualization maps of the cooperative relationship between relevant countries, institutions, and authors (co-authorship), the frequency of different keywords appearing together (co-occurrence), and the frequency of different articles cited together (co-cited). Arcgis 10.8 created the world map of publications distribution in this field and Histcite pro 2.1 was used to count the local citation score (LCS) of references. In addition, Journal Citation Reports were used to consult the latest journal import factor and JCI quartile.ResultsAs of June 30, 2022, from the Web of Science core collection, we selected 2,474 original articles in English, excluding the document types of the news items, meeting abstracts, and some articles that had little relevance to our theme. The United States acted as the leader and enjoyed a high reputation in this field. The University of California System was the institution that made the greatest contribution (3.64% with 90 papers). Most articles were published in the Journal of Alzheimer’s Disease (8.21%, with 203 papers). The most frequently co-cited journal in Q1 was the Journal of Biological Chemistry (8,666 citations, TLS: 1039591). Russel H. Swerdlow (55 publications) was the most productive author and PH Reddy was the most co-cited author with 1,264 citations (TLS: 62971). The hotpots of mitochondrial dysfunction in AD were as follows: “oxidative stress,” “amyloid-beta-protein,” “tau,” “apoptosis,” “inflammation,” “autophagy,” “precursor protein,” “endoplasmic-reticulum,” “dynamics” and “mitochondrial unfolded protein response.”ConclusionThis bibliometric analysis research will help readers rapidly identify current hotpots and milestone studies related to directions of interest in AD research.

Background: mortality rates are usually influenced by the variations of environmental factors. However, there are few studies on the impact of sunlight duration induced mortality. In this study, we examine provincial level associations between the sunshine duration and crude mortality rates. Methods: we use China mortality data from the National Bureau of Statistics of China combined with China census data and data from the China Meteorological Data Service Centre. Annual mortality rates for 31 provinces, autonomous regions, and municipalities in China from 2005 to 19. Data are analyzed at the provincial level by using panel regression methods. The main outcome measures are the mortality rates associated with average daily sunshine duration. Then we perform a series of sentimental analyses. Results: the average daily sunshine duration ratio cubed is positively associated with provincial level mortality rates (β = 11.509, 95% confidence interval 1.869 to 21.148). According to this estimate, increasing 2.895 h of additional daily sunshine is associated with an estimated 1.15% increase in the crude mortality rates. A series of sensitivity analyses show a consistent pattern of associations between average daily sunshine duration ratio cubed and mortality rates. Conclusions: more sunshine duration is associated with increased mortality rates. While the associations documented cannot be assumed to be causal, they suggest a potential association between increased sunshine duration and increased mortality rates.

Introduction: Enhancing the green total factor productivity of dairy cows (GPDC) is crucial for fostering the low-carbon sustainable development of the dairy industry.Methods: This research utilizes the Minimum distance to weak efficient frontier–Meta frontier–Malmquist–Luenberger (MinDW-MML) index to examine the GPDC using the unbalanced panel data on dairy cows in 26 provinces of China from 2004 to 2020, taking into account regional heterogeneity and unexpected output.Results: The findings revealed that 1) from 2004 to 2020, China’s GPDC displayed a fluctuating and declining trend, with the steepest decrease occurring from 2007 to 2010 (2.26% at the common frontier and 1.81% at the group frontier). The fundamental cause of the low GPDC, as seen from the standpoint of efficiency decomposition, is technical advancement (technological change, or TC); 2) the GPDC exhibits a declining trend from east to west to central China for the two-level frontier. The eastern region benefits clearly from technological advancement (TC) and improved technical performance (EC), while the middle and western regions are mostly constrained by TC; and 3) the GPDC displayed regional heterogeneity at several scales. Although the efficiency values of medium- and small-scale aquaculture were low and large-scale aquaculture GPDC in the eastern and western regions was greater than 1, the GPDC did not reach the effective state in the central region.Discussion: Based on these findings, we propose policy recommendations such as promoting technological innovation and low-carbon technology in dairy farming, improving the technical system of dairy farming, and optimizing the industrial layout of dairy farming, which will serve as a model for future high-quality and sustainable dairy farming development in China, and provide an experience for green dairy farming development in other countries.

PurposeProsocial behavior (PSB) plays a critical role in everyday society, especially during the pandemic of COVID-19. Understanding the underlying mechanism will provide insight and advance its implementation. According to the theory of PSB, social interaction, family and individual characters all contribute to its development. The current study aimed to investigate the influencing factor of PSB among Chinese college students during COVID-19 outbreak. This is an attempt to understand the mechanism of PSB and to provide a reference for the formulation of policies aimed at promoting healthy collaborative relationships for college students.MethodThe online questionnaire was administered to 664 college students from 29 provinces of China via Credamo platform. There were 332 medical students and 332 non-medical students aged between 18 and 25 included for final study. The mediating role of positive emotion/affect (PA) and the moderating role of parental care in the association between social support and PSB during the pandemic of COVID-19 was explored by using Social Support Rate Scale (SSRS), Prosocial Tendencies Measurement Scale (PTM), The Positive and Negative Affect (PANAS), as well as Parental Bonding Instrument (PBI). The process macro model of SPSS was adopted for mediating and moderating analysis.ResultsThe results showed that social support positively predicted PSB among Chinese college students, even after adding PA as a mediation variable. PA during COVID-19 mediated the association between social support and PSB. PSB also revealed as a predictor of PA by regression analysis. Moreover, the moderating effect of parental care in the relationship between PA and PSB was detected.ConclusionPA under stress acts as a mediator between social support and PSB. This mediating effect was moderated by PC in childhood. In addition, PSB was observed to predict PA reversely. The promoting factors and path between the variables of PSB are complex and need to be explored extensively. The underlying factors and process should be further investigated for the development of intervention plans.

Background: The characteristics of patients with eosinophilia are heterogeneous and the outcomes can vary from asymptomatic to severe. Objective: To describe the feature of patients with eosinophilia in a single center. Design: Based on the electronic medical records from Yangjiang People's Hospital in China, the inpatients admitted between June 2018 and February 2021 with measured blood eosinophil counts were evaluated. Methods: Eosinophilia was defined as a peripheral blood eosinophil count of ≥0.5 × 109/L. Differences were compared by eosinophilia severity. The medical records of patients with moderate to severe eosinophilia were reviewed and summarized in terms of examination, diagnoses and management. And these patients were matched with patients without incidental eosinophilia by propensity score and the differences were compared. Results: A total of 7,835 patients with eosinophilia were identified out of 131,566 total inpatients. All types of eosinophilia were most common in males (8.2%; 5,351/65,615), and in patients aged 0–6 years (11.6%; 1,760/15,204), and in the pediatric (10.8%; 1,764/16,336) department, followed by dermatology (10.6%; 123/1,162), Oncology (7.5%; 394/5,239) and Intensive care unit (ICU) (7.4%; 119/1,608). Patients with moderate to severe eosinophilia were more likely to admit to ICU (moderate: 1.3%; severe: 0.50%). In patients with moderate to severe eosinophilia, only 205/621 (33%) had eosinophilia mentioned in their records, and only 63/621 (10.1%) underwent investigations for eosinophilia. The majority of patients with moderate to severe eosinophilia (372/621, 59.9%) had an infectious disease, and little examination (7.4%; 46/621) was taken to identify the cause of eosinophilia, and only 39/621 (6.3%) of patients had a discrete cause of eosinophilia identified. Patients with moderate to severe eosinophilia (24.3%; 151/621) exhibited certain chance to have organ dysfunction. Conclusion: Incidental eosinophilia in inpatients was frequently neglected and less investigated. Multidisciplinary consultation may improve outcomes of inpatients with moderate to severe eosinophilia.

Introduction Patients with a mediastinal mass are at risk of pulmonary complications in the perioperative period. Preoperative spirometry tests are recommended in patients scheduled for thoracic surgery. Our objective is to investigate the association between preoperative spirometry results and the incidence of postoperative pulmonary complications in patients following mediastinal mass resection, which may determine the usefulness of spirometry tests in the prediction of the perioperative respiratory risk.Methods and analysis This protocol describes a retrospective cohort study of patients with mediastinal masses in Shanghai Pulmonary Hospital between 1 September 2021 and 1 September 2022, with a planned sample size of 660 patients. The primary aim of this study is to explore the association between preoperative spirometry results and the occurrence of postoperative pulmonary complications after mediastinal mass resection. Logistic regression analysis will be used to calculate the adjusted incidence rate difference and incidence rate ratios (with 95% CIs).Ethics and dissemination The study was approved by the ethics committee of Shanghai Pulmonary Hospital (K21-372Y). The results of the study will be submitted to a peer-reviewed biomedical journal for publication and presented at relevant conferences.

BackgroundEnvironmental noise exposure is linked to neuroinflammation and imbalance of the gut microbiota. Promoting gut microbiota homeostasis may be a key factor in relieving the deleterious non-auditory effects of noise. This study aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) intervention on noise-induced cognitive deficits and systemic inflammation in rats.MethodsLearning and memory were assessed using the Morris water maze, while 16S rRNA sequencing and gas chromatography-mass spectrometry were used to analyze the gut microbiota and short-chain fatty acid (SCFA) content. Endothelial tight junction proteins and serum inflammatory mediators were assessed to explore the underlying pathological mechanisms.ResultsThe results indicated that Lactobacillus rhamnosus GG intervention ameliorated noise-induced memory deterioration, promoted the proliferation of beneficial bacteria, inhibited the growth of harmful bacteria, improved dysregulation of SCFA-producing bacteria, and regulated SCFA levels. Mechanistically, noise exposure led to a decrease in tight junction proteins in the gut and hippocampus and an increase in serum inflammatory mediators, which were significantly alleviated by Lactobacillus rhamnosus GG intervention.ConclusionTaken together, Lactobacillus rhamnosus GG intervention reduced gut bacterial translocation, restored gut and blood-brain barrier functions, and improved gut bacterial balance in rats exposed to chronic noise, thereby protecting against cognitive deficits and systemic inflammation by modulating the gut-brain axis.

Background Mismatch repair deficiency (dMMR) is a well-recognized biomarker for response to immune checkpoint blockade (ICB). Strategies to convert MMR-proficient (pMMR) to dMMR phenotype with the goal of sensitizing tumors to ICB are highly sought. The combination of bromodomain containing 4 (BRD4) inhibition and ICB provides a promising antitumor effect. However, the mechanisms underlying remain unknown. Here, we identify that BRD4 inhibition induces a persistent dMMR phenotype in cancers.Methods We confirmed the correlation between BRD4 and mismatch repair (MMR) by the bioinformatic analysis on The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium data, and the statistical analysis on immunohistochemistry (IHC) scores of ovarian cancer specimens. The MMR genes (MLH1,MSH2,MSH6,PMS2) were measured by quantitative reverse transcription PCR, western blot, and IHC. The MMR status was confirmed by whole exome sequencing, RNA sequencing, MMR assay and hypoxanthine-guanine phosphoribosyl transferase gene mutation assay. The BRD4i AZD5153 resistant models were induced both in vitro and in vivo. The transcriptional effects of BRD4 on MMR genes were investigated by chromatin immunoprecipitation among cell lines and data from the Cistrome Data Browser. The therapeutic response to ICB was testified in vivo. The tumor immune microenvironment markers, such as CD4, CD8, TIM-3, FOXP3, were measured by flow cytometry.Results We identified the positive correlation between BRD4 and MMR genes in transcriptional and translational aspects. Also, the inhibition of BRD4 transcriptionally reduced MMR genes expression, resulting in dMMR status and elevated mutation loads. Furthermore, prolonged exposure to AZD5153 promoted a persistent dMMR signature both in vitro and in vivo, enhancing tumor immunogenicity, and increased sensitivity to α-programmed death ligand-1 therapy despite the acquired drug resistance.Conclusions We demonstrated that BRD4 inhibition suppressed expression of genes critical to MMR, dampened MMR, and increased dMMR mutation signatures both in vitro and in vivo, sensitizing pMMR tumors to ICB. Importantly, even in BRD4 inhibitors (BRD4i)-resistant tumor models, the effects of BRD4i on MMR function were maintained rendering tumors sensitive to ICB. Together, these data identified a strategy to induce dMMR in pMMR tumors and further, indicated that BRD4i sensitive and resistant tumors could benefit from immunotherapy.

A 50-year-old male patient was admitted to the Cardiology Department of our hospital for intermittent chest pain for 9 days. Coronary angiography showed approximately 70% stenosis in the middle part of the left anterior descending branch. When the procedure was about to end, the patient experienced dyspnea, facial flushing and fall of blood pressure suddenly. At this time, the angiography showed severe spasm and stenosis of the left coronary artery. With antianaphylaxis, pressor therapy, fluid resuscitation and intracoronary administration of nitroglycerin, the left coronary spasm was relieved. A diagnosis of type II kounis syndrome induced by ioversol with cardiogenic shock was made.

IntroductionDietary tryptophan (Trp) has been shown to influence fish feed intake, growth, immunity and inflammatory responses. The purpose of this study was to investigate the effect and mechanism of Trp on immune system of juvenile northern snakehead (Channa argus Cantor, 1842).MethodsA total of 540 fish (10.21 ± 0.11 g) were fed six experimental diets containing graded levels of Trp at 1.9, 3.0, 3.9, 4.8, 5.9 and 6.8 g/kg diet for 70 days, respectively.Results and DiscussionThe results showed that supplementation of 1.9-4.8 g/kg Trp in diets had no effect on the hepatosomatic index (HSI) and renal index (RI), while dietary 3.9 and 4.8 g/kg Trp significantly increased spleen index (SI) of fish. Dietary 3.9, 4.8, 5.9 and 6.8 g/kg Trp enhanced the total hemocyte count (THC), the activities of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD). Malondinaldehyde (MDA) levels in the blood were significantly decreased by consuming 3.9 and 4.8 g/kg Trp. Fish fed with 3.0 and 3.9 g/kg Trp diets up-regulated interleukin 6 (il-6) and interleukin 8 (il-8) mRNA levels. The expression of tumor necrosis factor α (tnf-α) was highest in fish fed with 3.0 g/kg Trp diet, and the expression of interleukin 1β (il-1β) was highest in fish fed with 3.9 g/kg Trp diet. Dietary 4.8, 5.9 and 6.8 g/kg Trp significantly decreased il-6 and tnf-α mRNA levels in the intestine. Moreover, Trp supplementation was also beneficial to the mRNA expression of interleukin 22 (il-22). Additionally, the mRNA expression levels of target of rapamycin (tor), toll-like receptor-2 (tlr2), toll-like receptor-4 (tlr4), toll-like receptor-5 (tlr5) and myeloid differentiation primary response 88 (myd88) of intestine were significantly up-regulated in fish fed 1.9, 3.0 and 3.9 g/kg Trp diets, and down-regulated in fish fed 4.8, 5.9 and 6.8 g/kg Trp diets. Dietary 4.8 and 5.9 g/kg Trp significantly increased the expression of inhibitor of nuclear factor kappa B kinase beta subunit (ikkβ) and decreased the expression of inhibitor of kappa B (iκbα), but inhibited nuclear transcription factor kappa B (nf-κb) mRNA level. Collectively, these results indicated that dietary 4.8 g/kg Trp could improve antioxidant capacity and alleviate intestinal inflammation associated with TOR and TLRs/MyD88/NF-κB signaling pathways.

Summary: Background: Faecal microbiota transplantation (FMT) has demonstrated efficacy in treating gastrointestinal (GI) diseases, such as Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). GI dysfunction is a frequent and occasionally dominating symptom of progressive supranuclear palsy-Richardson's syndrome (PSP-RS). However, it is not known whether FMT has clinical efficacy for PSP-RS. Methods: This 36-week, randomised, placebo-controlled, parallel-group, phase 2 clinical trial was performed at a university tertiary referral hospital in China. From August 15 2021 to December 31 2021, a total of 68 newly diagnosed patients with PSP-RS (male 40 [59%], female 28 [41%]) who had never received any antiparkinsonian medications were enrolled and randomly assigned to receive either healthy donor FMT (n = 34, FMT group) or a mixture of 0.9% saline and food colouring (E150c) as sham transplantation (n = 34, placebo group) through transendoscopic enteral tubing (TET). Two days after oral antibiotics, participants received 1 week of transplantation. After an interval of 4 weeks, retransplantation was performed. Then, the last transplantation was given after another interval of 4 weeks, and the participants were followed up for 24 weeks (week 36). Clinicaltrials.gov identifier: ChiCTR-2100045397. Findings: Among 68 patients who were randomised (mean age, 67.2 (SD 5.1); 40 [59%] were male, 28 [41%] were female), 63 participants completed the trial. Efficacy analyses were performed on the intention-to-treat (ITT) analysis set. At week 16, the mean PSP Rating Scale (PSPRS) scores (the primary outcome) improved from 40.1 (SD 7.6) to 36.9 (SD 5.9) in the FMT group, whereas the scores changed from 40.1 (SD 6.9) to 41.7 (SD 6.2) in the placebo group, for a treatment benefit of 4.3 (95% CI, 3.2–5.4) (P

The grain aphid Sitobion miscanthi is a serious pest of wheat that causes severe economic damage by sucking phloem sap and transmitting plant viruses. Here, two putative salivary effector homologs from S. miscanthi (Sm10 and SmC002) were selected based on sequence similarity to other characterized aphid candidate effectors. These effectors were then delivered into wheat cells separately via the type III secretion system of Pseudomonas fluorescens to elucidate their functions in the regulation of plant defenses and host fitness. The results showed that the delivery of either Sm10 or SmC002 into wheat plants significantly suppressed callose deposition and affected the transcript levels of callose synthase genes. The expression levels of salicylic acid (SA)-associated defense genes were upregulated significantly in wheat leaves carrying either Sm10 or SmC002. Moreover, LC-MS/MS analysis revealed that wheat SA levels significantly increased after the delivery of the two effectors. The results of aphid bioassays conducted on the wheat plants carrying Sm10 or SmC002 showed significant increases in the survival and fecundity of S. miscanthi. This study demonstrated that the Sm10 and SmC002 salivary effectors of S. miscanthi enhanced host plant susceptibility and benefited S. miscanthi performance by regulating wheat defense signaling pathways.

Abstract Antibody‐based therapies could be led astray when target receptors are expressed on nontarget sites, and the on‐target toxicity poses critical challenges to clinical applications. Here, a biomimetic indirect active targeting (INTACT) strategy is proposed based on receptor expression disparities between nontarget sites and the targets. By prebinding the antibodies using cell membrane vesicles with appropriate receptor expressions, the INTACT strategy could filter out the interactions on nontarget sites due to their inferior receptor expression, whereas ensure on‐demand release at the targets by competitive binding. The strategy is verified on CD47 antibody, realizing drastic alleviation of its clinically concerned hematotoxicity on a series of animal models including humanized patient‐derived xenograft platforms, accompanied by preferable therapeutic effects. Furthermore, the INTACT strategy proves extensive applicability for various systems including antibody, antibody–drug conjugate, and targeted delivery systems, providing a potential platform refining the specificity for frontier antibody‐related therapies.

IntroductionGeneralized anxiety disorder (GAD) is one of the most enduring anxiety disorders, being associated with increased systemic inflammation. However, the trigger and mechanisms underlying the activation of inflammatory cytokine responses in GAD remain poorly understood.Materials and methodsWe characterized the ear canal microbiome in GAD patients through 16S rRNA gene sequencing and metagenomic sequencing and identified the serum inflammatory markers in GAD patients. Spearman correlations were applied to test the relationship between the microbiota changes and systemic inflammation.ResultsOur findings showed the higher microbial diversity, accompanied with the significantly increased abundance of Proteobacteria, and decreased abundance of Firmicutes in the ear canal of GAD participants compared to that of the age- and sex-matched healthy controls (HC). Metagenomic sequencing showed that Pseudomonas aeruginosa were significantly increased at species-level in GAD patients. Furthermore, we observed the relative abundance of Pseudomonas aeruginosa was positively associated with elevated systemic inflammatory markers and the severity of disease, suggesting that these ear canal microbiota alterations might be correlated with GAD by activating the inflammatory response.ConclusionsThese findings indicate that microbiota-ear-brain interaction via upregulating inflammatory reaction involve in the development of GAD, as well as suggest that ear canal bacterial communities may be a target for therapeutic intervention.

Microcystin-LR (MC-LR), one of aquatic environmental contaminants with reproductive toxicity produced by cyanobacterial blooms, but its toxic effects and mechanisms on the ovary are not fully understood. Here, proteomic techniques and molecular biology experiments were performed to study the potential mechanism of MC-LR-caused ovarian toxicity. Results showed that protein expression profile of ovarian granulosa cells (KK-1) was changed by 17 μg/mL MC-LR exposure. Comparing with the control group, 118 upregulated proteins as well as 97 downregulated proteins were identified in MC-LR group. Function of differentially expressed proteins was found to be enriched in pathways related to adherent junction, such as cadherin binding, cell-cell junction, cell adhesion and focal adherens. Furthermore, in vitro experiments, MC-LR significantly downregulated the expression levels of proteins associated with adherent junction (β-catenin, N-cadherin, and α-catenin) as well as caused cytoskeletal disruption in KK-1 cells (P

Abstract The use of systems‐based pharmacological modeling approaches to characterize mode‐of‐action and concentration‐effect relationships for drugs on specific hemodynamic variables has been demonstrated. Here, we (i) expand a previously developed hemodynamic system model through integration of cardiac output (CO) with contractility (CTR) using pressure‐volume loop theory, and (ii) evaluate the contribution of CO data for identification of system‐specific parameters, using atenolol as proof‐of‐concept drug. Previously collected experimental data was used to develop the systems model, and included measurements for heart rate (HR), CO, mean arterial pressure (MAP), and CTR after administration of atenolol (0.3–30 mg/kg) from three in vivo telemetry studies in conscious Beagle dogs. The developed cardiovascular (CVS)‐contractility systems model adequately described the effect of atenolol on HR, CO, dP/dtmax, and MAP dynamics and allowed identification of both system‐ and drug‐specific parameters with good precision. Model parameters were structurally identifiable, and the true mode of action can be identified properly. Omission of CO data did not lead to a significant change in parameter estimates compared to a model that included CO data. The newly developed CVS‐contractility systems model characterizes short‐term drug effects on CTR, CO, and other hemodynamic variables in an integrated and quantitative manner. When the baseline value of total peripheral resistance is predefined, CO data was not required to identify drug‐ and system‐specific parameters. Confirmation of the consistency of system‐specific parameters via inclusion of data for additional drugs and species is warranted. Ultimately, the developed model has the potential to be of relevance to support translational CVS safety studies.

Coenzyme Q10 is a fat-soluble vitamin-like benzoquinone compound, which is synthesized endogenously from tyrosine in human body. It has many physiological functions, such as participating in ATP production capacity, scavenging free radicals and anti-oxidantion, enhancing immunity, stabilizing cell membranes and so on. Since the first coenzyme Q10 health food was approved in 2003, and by 2020, coenzyme Q10 was used as raw material for record management. China has approved 171 coenzyme Q10 health foods. In order to better understand the current situation of approved coenzyme Q10 health foods, the author took the research work of coenzyme Q10 health food raw materials list project which I participated in tracking as the starting point, based on the original China Food and Drug Administration website and the date of approved products from 1996 to 2020 published on the website of the State Administration of Market Supervision, combined with the actual registration review work and related research status, comprehensively analyzed the review and approval of coenzyme Q10 health foods in the past 20 years from the aspects of safety, function claims, and quality control. The author also proposed some opinions and suggestions on strengthening the study of the published coenzyme Q10 raw material catalogue, and to explore the inclusion of amino acids, probiotics, protein and other dietary nutrients into the raw material catalogue management, pay attention to the construction of the exclusive quality standard system of dietary supplement raw materials.

Engineering a complete, physiologically functional, periodontal complex structure remains a great clinical challenge due to the highly hierarchical architecture of the periodontium and coordinated regulation of multiple growth factors required to induce stem cell multilineage differentiation. Using biomimetic self-assembly and microstamping techniques, we construct a hierarchical bilayer architecture consisting of intrafibrillarly mineralized collagen resembling bone and cementum, and unmineralized parallel-aligned fibrils mimicking periodontal ligament. The prepared biphasic scaffold possesses unique micro/nano structure, differential mechanical properties, and growth factor-rich microenvironment between the two phases, realizing a perfect simulation of natural periodontal hard/soft tissue interface. The interconnected porous hard compartment with a Young's modulus of 1409.00 ± 160.83 MPa could induce cross-arrangement and osteogenic differentiation of stem cells in vitro, whereas the micropatterned soft compartment with a Young's modulus of 42.62 ± 4.58 MPa containing abundant endogenous growth factors, could guide parallel arrangement and fibrogenic differentiation of stem cells in vitro. After implantation in critical-sized complete periodontal tissue defect, the biomimetic bilayer architecture potently reconstructs native periodontium with the insertion of periodontal ligament fibers into newly formed cementum and alveolar bone by recruiting host mesenchymal stem cells and activating the transforming growth factor beta 1/Smad3 signaling pathway. Taken together, integration of self-assembly and microstamping strategies could successfully fabricate a hierarchical bilayer architecture, which exhibits great potential for recruiting and regulating host stem cells to promote synergistic regeneration of hard/soft tissues.

Households represent a large share of flexibility on the demand side for assisting the smooth operation of the highly renewable grid. The stochastic nature of activities and various appliance usage patterns of household occupants affects the flexibility potential greatly, but is usually oversimplified in the existing research. This paper aims to propose a novel method for simulating the dynamics of household energy-related activities and appliance usage, which provides realistic synthetic load profiles for smart energy management. To this aim, a highly resolved multi-agent system model is proposed, which comprises an Agent-Based Activity Chain Model (ABACM) and 34 types of common household appliance models. Firstly, the patterns of various occupant behaviors are obtained through mining of real-world residential time-of-use data. Then, the stochastic activity profiles of occupants are generated using the ABACM, with a root mean square error of 0.95%. Finally, the electricity consumption profiles of household appliances are simulated based on specific energy-related activities. The proposed method is validated and proved to be able to capture stochastic occupant behaviors and represent the dynamics of residential energy consumption. The future work will focus on using the proposed model for exploring the potential of residential demand response.

Abstract Two-dimensional (2D) molybdenum disulfide (MoS2) has been recognized as a potential substitution of platinum (Pt) for electrochemical hydrogen evolution reaction (HER). However, the broad adoption of MoS2 is hindered by its limited number of active sites and low inherent electrical conductivity. In this work, we employed a one-step solvothermal synthesis technique to construct a ternary hybrid structure consisting of dual-phase MoS2, titanium carbide (Ti3C2) MXene, and carbon nanotubes (CNTs), and demonstrated synergistic effects for active site exposure, surface area enlargement, and electrical conductivity improvement of the catalyst. The dual-phase MoS2 (DP-MoS2) is directly formed on the MXene with CNTs acting as crosslinks between 2D islands. The existence of edge-enriched metallic phase MoS2, the conductive backbone of MXene along with the crosslink function of CNTs clearly improves the overall HER performance of the ternary nanocomposite. Moreover, the integration of MoS2 with MXene not only increases the interlayer distance of the 2D layers but also partially suppresses the MXene oxidation and the 2D layer restacking, leading to good catalytic stability. As a result, an overpotential of 169 mV and a low Tafel slope of 51 mV/dec was successfully achieved. This work paves a way for 2D-based electrocatalyst engineering and sheds light on the development of the next-generation noble metal-free HER electrocatalysts.

As the deficiency of learning ability of traditional semi-supervised depth anomaly detection model to unbalanced multidimensional data distribution and the difficulty of model training, a multi-dimensional time series anomaly detection method based on VAE-WGAN architecture was proposed.VAE was used as a generator of WGAN.The Wasserstein distance was used as a measure between the model fitting distribution and the real distribution of the data to be measured, complex and high-dimensional data distributions could be learned.A sliding window was applied to divide the time series, the normal sequence data were used to train the model.According to the abnormal score of the waiting test sequence in the trained model, the anomaly was judged with adaptive threshold technology.The experimental results show that the model is easy to train and stable, and has obvious improvement over the existing generative anomaly detection model in accuracy, recall rate, F1 score and other anomaly detection performance indicators.

Ultraviolet (UV)-induced photoaging skin has become an urgent issue. The functional foods and cosmetics aiming to improve skin photoaging are developing rapidly, and the demand is gradually increasing year by year. Collagen peptides have been proven to display diverse physiological activities, such as excellent moisture retention activity, hygroscopicity, tyrosinase inhibitory activity and antioxidant activity, which indicates that they have great potential in amelioration of UV-induced photoaging. The main objective of this article is to recap the main mechanisms to improve photoaging skin by collagen peptides and their physiological activities in photo-protection. Furthermore, the extraction and structural characteristics of collagen peptides are overviewed. More importantly, some clinical trials on the beneficial effect on skin of collagen peptides are also discussed. In addition, prospects and challenges of collagen peptides are emphatically elucidated in this review. This article implies that collagen peptides have great potential as an effective ingredient in food and cosmetics industry with a wide application prospect.

Abstract In the application of internet of vehicles system, it is particularly important to obtain real-time and effective vehicle information and provide personalized functional services for vehicle operation. This algorithm combines knowledge graph technology with convolutional network and presents a new algorithm model, that is, when calculating the representation of a given entity in the knowledge graph, the information of the neighboring entity is combined with the deviation. Through the integration of neighbor entity information, the local neighborhood structure can be better captured and stored in each entity, and the weight of different neighbor entities depends on the relationship between them and the specific user, which can better reflect the user's personalized interests, in order to fully demonstrate the characteristics of the entity. Compared with the traditional coordinated filtering technology SVD model, this model has improved accuracy and F1 value.

Abstract Dynamic regulation of QTLs remains mysterious. Single segment substitution lines (SSSLs) and conditional QTL mapping and functional QTL mappings are ideal materials and methods to explore dynamics of QTLs for complex traits. This paper analyzed the dynamics of QTLs on plant height with SSSLs in rice. Five SSSLs were verified with plant height QTLs first. All five QTLs had significant positive effects at one or more developmental stages except QTL1. They interacted each other, with negative effects before 49 d after transplanting and positive effects since then. The five QTLs selectively expressed in specific periods, mainly in the periods from 35 to 42 d and from 49 to 56 d after transplanting. Expressions of epistasis were dispersedly in various periods, negative effects appearing mainly before 35 d. The five QTLs brought the inflexion point ahead of schedule, accelerated growth and degradation, and changed the peak plant height, while their interactions had the opposite effects. The information will be helpful to understand the genetic mechanism for developmental traits.

This paper proposes an active–reactive power collaborative scheduling model with cluster division for the flexible distributed energy resources (DERs) of smart-building systems to resolve the high complexity of the centralized optimal scheduling of massive dispersed DERs in the distribution network. Specifically, the optimization objective of each cluster is to minimize the operational cost, the power-loss cost, and the penalty cost for flexibility deficiency, and the second-order cone-based branch flow method is utilized to convert the power-flow equations into linearized cone constraints, reducing the nonlinearity and heavy computation burden of the scheduling model. Customized virtual battery models for building-integrated flexible DERs are developed to aggregate the power characteristics of flexible resources while quantifying their regulation capacities with time-shifting power and energy boundaries. Moreover, a cluster division algorithm considering the module degree index based on the electrical distance and the flexible balance contribution index is formulated for cluster division to achieve information exchange and energy interaction in the distribution network with a high proportion of building-integrated flexible DERs. Comparative studies have demonstrated the superior performance of the proposed methodology in economic merits and voltage regulation.

Sheep and goat meats are increasingly popular worldwide due to their superior nutritional properties and distinctive flavor profiles. In recent decades, substantial progress in meat science has facilitated in-depth examinations of ovine and caprine muscle development during the antemortem phase, as well as post-mortem changes influencing meat attributes. To elucidate the intrinsic molecular mechanisms and identify potential biomarkers associated with meat quality, the methodologies employed have evolved from traditional physicochemical parameters (such as color, tenderness, water holding capacity, flavor, and pH) to some cutting-edge omics technologies, including transcriptomics, proteomics, and metabolomics approaches. This review provides a comprehensive analysis of multi-omics techniques and their applications in unraveling sheep and goat meat quality attributes. In addition, the challenges and future perspectives associated with implementing multi-omics technologies in this area of study are discussed. Multi-omics tools can contribute to deciphering the molecular mechanism responsible for the altered the meat quality of sheep and goats across transcriptomic, proteomic, and metabolomic dimensions. The application of multi-omics technologies holds great potential in exploring and identifying biomarkers for meat quality and quality control, thereby promoting the optimization of production processes in the sheep and goat meat industry.

Cattleyak, the interspecies hybrid from cattle (males) and yak (females), displays a faster growth rate and higher feeding efficiency than yak with usually one-year shorter raising cycle. This study aimed to assess the carcass characteristics and meat quality attributes of cattleyak by compared to yak at a similar bodyweight. Results showed that cattleyak exhibited an elevated dressing percentage (58.33%) and a significantly higher content of healthy fatty acids, including eicosapentaenoic acid (5.64%) and docosahexaenoic acid (0.46%) (P < 0.05). Compared to yak meat, the tenderness of cattleyak meat was significantly enhanced (P < 0.05), with the lower Warner-Bratzler shear force (59.53 N) and hardness value (580.92 g), as well as the significant reduction of more than 20% of muscle fiber diameter (P < 0.05). Additionally, myofibrillar proteins in cattleyak, including desmin, tropomyosin, and troponin-T, degraded faster than those in yak (P < 0.05), indicating their role in tenderization improvement in cattleyak. These findings suggest that, in comparison to yaks of the similar bodyweight, cattleyaks with less than one year of the raising cycle have improved meat quality and economic efficiency.

In order to solve the safety problems that exist in traditional charging technology, a new visible light-curing 3D printing platform and energetic slurry formula were designed. Within them, the formula of light-curing slurry is 60.46% EA/PUA (prepolymer), 37.21% PETA/HDDA/BA (active diluent monomer), 0.47% CQ (visible light initiator), 0.93% DMT (curing accelerator), and 0.93% additive. The curing time of visible light-curing paste is 7.5 s, the viscosity is 22 6 mPa·s, the curing hardness is 2 H, the gel rate is 96.67%, the shrinkage rate is 98.35%, and the curing depth is 9.41 mm. The optimal formulation of energetic slurry is 20% visible light-curing slurry, 57.72% AP, 15.28% Al and 7% RDX. The 3D printing energetic powder column has a smooth surface, uniform filler distribution, a flat surface, no protrusions or other defects, and good matching. The average burning rate is 1.165 mm·s−1, the combustion is stable, and the maximum burning light intensity is 2.053 cd.

Objective The study aim was to evaluate the clinical outcomes, functional outcomes, and postoperative complications of anchor and Krackow‐“8” suture fixation (AS) and K‐wire fixation in patients with distal pole patellar fractures. Methods Twenty‐eight patients with distal pole patella fractures between January 2011 and December 2014 were reviewed retrospectively. The anchor and Krackow‐“8” suture fixation (AS group) was applied in 10 patients and 18 patients underwent K‐wire fixation (K‐wire group). The average age of patients was 46.000 ± 19.476 years in the AS group and 47.556 ± 15.704 years in the K‐wire group, with comparable demographic characteristics. All patients underwent regular follow‐up the operative data and postoperative functional and clinical outcomes were recorded. Complications were recorded by clinical and radiographic assessment. Bostman patellar fracture functional score was used to evaluate knee function after patellar fracture. Results A total of 28 eligible patients were included in this study. The mean follow‐up was similar for the AS and the K‐wire groups (P > 0.05). The incision length of AS group was significantly smaller than that of K‐wire group (P < 0.05). The incision length of AS group was significantly smaller than that of K‐wire group (P < 0.05). The final follow‐up on the range of motion of the knee: the average extension lag was similar in two groups (P > 0.05); flexion and flexion–extension angle was slightly better in the AS group than in the K‐wire group. The Bostman patella fracture functional score of AS group were better than K‐wire group at 3 and 6 months after operation. Four kinds of postoperative complications in two groups, one patient (10%) in the AS group and two patients (11.1%) in the K‐wire group had infections. Two (11.1%) cases of nonunion in group K and three patients (16.7%) required re‐operation: one due to infection and two due to early implant failure. In the AS group, all distal pole fractures of the patella showed bony union, without loosening, falling, pulling out and nonunion of the fractures 6 months after operation. Conclusions Anchor and Krackow‐“8” suture fixation is an easily executed surgical procedure that can significantly reduce incision length and achieve better surgical outcomes than traditional procedures with regard to postoperative complications, knee function and without requiring a second operation. This technique is an effective operation method for the treatment of inferior patellar pole fractures.

The marine environmental observing data play an important role on the scientific research, environment safety, rights maintenance and synthetic decision support.The most widely used marine environmental observing data in the world are produced, shared and updated by the marine science and technology developing countries.However, few are produced by our country.Taking the marine environmental observing data as examples, the characteristics, quality control workflow, management, application and sharing of the representative datasets were systematically reviewed.In addition, the present status of the domestic research and the existing problems were introduced.Moreover, related suggestions were also put forward on the sharing mechanism, platform development and data producing.

Abstract Background Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, most of which are caused by atherosclerosis. Discerning processes that participate in macrophage-to-foam cell formation are critical for understanding the basic mechanisms underlying atherosclerosis. To explore the molecular mechanisms of foam cell formation, differentially expressed proteins were identified. Methods Human peripheral blood mononuclear cells were stimulated with macrophage colony-stimulating factor, and obtained macrophages were transformed into foam cells by oxidized low-density lipoprotein. Tandem mass tag (TMT) labeling combined with mass spectrometry was performed to find associations between foam cell transformation and proteome profiles. Results Totally, 5146 quantifiable proteins were identified, among which 1515 and 182 differentially expressed proteins (DEPs) were found in macrophage/monocyte and foam cell/macrophage, respectively. Subcellular localization analysis revealed that downregulated DEPs of macrophages/monocytes were mostly located in the nucleus, whereas upregulated DEPs of foam cells/macrophages were mostly extracellular or located in the plasma membrane. Functional analysis of DEPs demonstrated that cholesterol metabolism-related proteins were upregulated in foam cells, whereas immune response-related proteins were downregulated in foam cells. The protein interaction network showed that the DEPs with the highest interaction scores between macrophages and foam cells were mainly concentrated in lysosomes and the endoplasmic reticulum. Conclusions Proteomics analysis suggested that cholesterol metabolism was upregulated, while the immune response was suppressed in foam cells. KEGG enrichment analysis and protein-protein interaction analysis indicated that DEPs located in the endoplasmic reticulum and lysosomes might be key drivers of foam cell formation. These data provide a basis for identifying the potential proteins associated with the molecular mechanism underlying macrophage transformation to foam cells.

Abstract Background In preimplantation genetic testing for aneuploidy (PGT-A), appropriate evaluation of mosaic embryos is important because of the adverse implications of transferring embryos with high-level mosaicism or discarding those with low-level mosaicism. Despite the availability of multiple reliable techniques for PGT-A, data comparing the detection of mosaicism using these techniques are scarce. To address this gap in the literature, we compared the detection ability of the two most commonly used PGT-A platforms, next-generation sequencing (NGS) and the single-nucleotide polymorphism (SNP) array, for mosaic embryos. Results We retrospectively reviewed the data of PGT-A or preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) conducted at our center from January 2018 to October 2020, and selected blastocysts that underwent aneuploidy screening with both an SNP array and NGS. Trophectoderm biopsy, multiple displacement amplification (MDA), and aneuploidy screening with an SNP array were conducted on the enrolled blastocysts. When the SNP array indicated mosaicism, NGS was performed on the corresponding MDA product for verification. Among the 105 blastocysts diagnosed with mosaicism with the SNP array, 80 (76.19%) showed mosaicism in NGS, with complete and partial concordance rates of 47.62% (50/105) and 18.10% (19/105), respectively. The complete discordance rate of the two platforms was 34.29% (36/105). That is, 10.48% (11/105) of the blastocysts were diagnosed with completely different types of mosaicism with the two platforms, while 13.33% (14/105) and 10.48% (11/105) of the embryos diagnosed as showing mosaicism with SNP were detected as showing aneuploidy and euploidy with NGS, respectively. Conclusions The consistency of NGS and the SNP array in the diagnosis of embryo mosaicism is extremely low, indicating the need for larger and well-designed studies to determine which platform is more accurate in detecting mosaic embryos.

Abstract Background Canine distemper virus (CDV), which is highly infectious, has caused outbreaks of varying scales in domestic and wild animals worldwide, so the development of a high-efficiency vaccine has broad application prospects. Currently, the commercial vaccine of CDV is an attenuated vaccine, which has the disadvantages of a complex preparation process, high cost and safety risk. It is necessary to develop a safe and effective CDV vaccine that is easy to produce on a large scale. In this study, sequences of CDV haemagglutinin (HA) from the Yanaka strain were aligned, and three potential linear sequences, termed YaH3, YaH4, and YaH5, were collected. To increase the immunogenicity of the epitopes, ferritin was employed as a self-assembling nanoparticle element. The ferritin-coupled forms were termed YaH3F, YaH4F, and YaH5F, respectively. A full-length HA sequence coupled with ferritin was also constructed as a DNA vaccine to compare the immunogenicity of nanoparticles in prokaryotic expression. Result The self-assembly morphology of the proteins from prokaryotic expression was verified by transmission electron microscopy. All the proteins self-assembled into nanoparticles. The expression of the DNA vaccine YaHF in HEK-293T cells was also confirmed in vitro. After subcutaneous injection of epitope nanoparticles or intramuscular injection of DNA YaHF, all vaccines induced strong serum titres, and long-term potency of antibodies in serum could be detected after 84 days. Strong anti-CDV neutralizing activities were observed in both the YaH4F group and YaHF group. According to antibody typing and cytokine detection, YaH4F can induce both Th1 and Th2 immune responses. The results of flow cytometry detection indicated that compared with the control group, all the immunogens elicited an increase in CD3. Simultaneously, the serum antibodies induced by YaH4F and YaHF could significantly enhance the ADCC effect compared with the control group, indicating that the antibodies in the serum effectively recognized the antigens on the cell surface and induced NK cells to kill infected cells directly. Conclusions YaH4F self-assembling nanoparticle obtained by prokaryotic expression has no less of an immune effect than YaHF, and H4 has great potential to become a key target for the easy and rapid preparation of epitope vaccines. Graphical Abstract

Abstract The upper sandy loess unit L9 on the Chinese Loess Plateau (CLP) corresponds to marine isotope stages 22–24, and it represents aeolian deposition under conditions of extreme aridification. However, the forcing mechanism remains controversial. Numerous paleomagnetic studies in the eastern CLP show that the coarsest part of L9 is remagnetized and has a normal geomagnetic polarity. However, our results show that in loess sections in the western CLP the coarsest part of L9 records a primary reverse polarity. This spatially inconsistent magnetization pattern originates mainly from the different magnetic carriers of the characteristic remanent magnetization (hematite in the western CLP and magnetite in the eastern CLP), which suggests a different dust provenance between the western and eastern CLP. We ascribe this spatial contrast in dust provenance to the episodic uplift of the northeastern Tibetan Plateau, which also led to the extreme aridification of the East Asian interior at ∼900 ka.

BackgroundHypertension, sleep disorders, and depression are highly prevalent in the elderly population and are all associated with cognitive impairment, but the role that sleep quality and depression play in the association between hypertension and cognitive impairment is unclear. The aim of this study was to investigate whether sleep quality and depression have a mediating role in the association between hypertension and cognitive impairment.MethodsA cross-sectional study was conducted to collect data from the Tongji Hospital Comprehensive Geriatric Assessment Database. Sleep quality, depression and cognitive function were measured by the Pittsburgh Sleep Quality Index (PSQI), the Geriatric Depression Scale (GDS-15) and the Mini-Mental State Examination (MMSE), respectively. Correlation analysis, regression analysis and Bootstrap analysis were used to examine correlations between key variables and mediating effects of sleep quality and depression. Adjustments for multiple comparisons were performed using Benjamini-Hochberg adjustment for multiple testing.ResultsA total of 827 participants were included, hypertension was present in 68.3% of the sample. After correcting for covariates, hypertensive patients aged 65 years or older had worse cognitive function, poorer-sleep quality and higher levels of depression. Sleep quality was significantly negatively associated with depression and cognitive function, while depression was negatively associated with cognitive function. Mediation analysis revealed that hypertension can affect cognitive function in older adults through a single mediating effect of sleep quality and depression and a chain mediating effect of sleep quality and depression.ConclusionThis study found that sleep quality and depression can mediate the relationship between hypertension and cognitive function in elderly. Enhanced supervision of sleep quality and depression in elderly patients with hypertension may be beneficial in maintaining cognitive function.

Introduction Opioid prescribing rates are disproportionately high in the North of England. In addition to patients’ complex health needs, clinician prescribing behaviour is also a key driver. Although strategies have been initiated to reduce opioid prescribing nationally, the COVID-19 pandemic has interrupted service provision and created challenges for the system and health professionals to tackle this complex issue. A pilot intervention using smartphone video messaging has been developed to remotely explain the rationale for opioid reduction and facilitate self-initiation of support. The aim of this study is to evaluate the potential benefits, risks and economic consequences of ‘at scale’ implementation.Methods and analysis This will be a mixed-methods study comprising a quasi-experimental non-randomised before-and-after study and qualitative interviews. The intervention arm will comprise 50 General Practitioner (GP) Practices using System 1 (a clinical computer system hosting the intervention) who will deliver the video to their patients via text message. The control arm will comprise 50 practices using EMIS (a different computer system) who will continue usual care. Monthly practice level prescribing and consultation data will be observed for 6 months postintervention. A general linear model will be used to estimate the association between the exposure and the main outcome (opioid prescribing; average daily quantity (ADQ)/1000 specific therapeutic group age-sex related prescribing unit). Semi-structured interviews will be undertaken remotely with purposively selected participants including patients who received the video, and health professionals involved in sending out the videos and providing additional support. Interviews will be audio recorded, transcribed and analysed thematically.Ethics and dissemination Ethics approval has been granted by the NHS Health Research Authority Research Ethics Committee (22/PR/0296). Findings will be disseminated to the participating sites, participants, and commissioners, and in peer-reviewed journals and academic conferences.Trial registration number NCT05276089.

Aspartokinase (AK) is synergistically suppressed by Thr and Lys in the Corynebacterium metabolic pathway. Site-directed mutations can significantly improve AK inhibition. Our previous studies confirmed that sites 379 and 380 were important sites affecting enzyme activity, so we further screen the double mutants with excellent enzymatic properties from sites 379 and 380, and discuss the difference of enzyme activity between the double mutants and single mutants. Here, a double mutant, T379L/A380 M, with improved enzyme activity (2.74-fold) was obtained. Enzymatic property experiments showed that the optimum temperature of T379L/A380 M increased from 26 °C (recombinant Escherichia coli; WT-AK) to 45 °C and that the optimal pH decreased from 8.0 (WT-AK) to 7.5. Further, the half-life decreased from 4.5 to 3.32 h. These enzymatic properties were better than other mutant strains. Inhibition was diminished with low concentrations of Lys, and Lys + Thr presented an activating role. Subsequently, the reasons for the improved AK enzyme activity were illustrated with microscale thermophoresis (MST) experiments and molecular dynamic (MD) simulation by measuring ligand affinity and AK conformational changes. MST showed that the affinity between T379L/A380 M and Lys decreased, but the affinity between T379L/A380 M and Asp increased, promoting T379L/A380 M enzyme activity. MD experiments showed that T379L/A380 M enhanced the Asp-ATP affinity and catalyzed the transfer of residues S192 and D193 to Asp, promoting T379L/A380 M enzyme activity. However, the mutation did not cause fluctuations in the substrate Asp and ATP pockets. This might be why the enzyme activity was inferior to that of the single mutants (T379L and A380 M).

Mechanoluminescence (ML) sensors offer full-field strain/stress measurements and have the advantages of easy implementation, non-invasiveness, and low cost. However, knowledge of the mechanism of carrier detrapping owing to mechanical forces remains elusive as it may include one or more complicated processes. Several attempts to develop calibration models for converting the light emitted by ML sensors into mechanical stress have been reported, but few studies have tested the ML response under static or quasi-static loading rates. In this study, we built a real-time measurement system to evaluate the constitutive strain-luminescence relationship of ML sensors. The ML response was investigated at loading rates as low as 5 µm/s (i.e., strain rates as low as 16.2 μst/s). The results showed that the light of ML sensors was still excited under quasi-static loading rates. A double-exponential function was applied to describe nonlinear changes in light intensity over time. We used this function to modify the previous model and predict the ML responses under variable loading rate conditions. The results predicted by the model proposed in this paper are in good agreement with the experimental results.

This study aimed to improve the aroma quality of blueberry wine by employing cultivar selection and precise berry sorting. We conducted a comprehensive analysis of volatile profiles in blueberry wines derived from nine cultivars commonly cultivated in the middle region of China. ‘Misty’ and ‘V3’ blueberry wines exhibited pronounced floral aromas, closely linked to elevated terpenoid and phenylacetaldehyde content. ‘Legacy’ and ‘Star’ displayed a distinct fruity aroma profile attributed to the presence of ethyl 2-methylbutyrate, ethyl phenylacetate, and diethyl succinate. ‘Jewel’ featured an intense buttery aroma, correlated with higher concentrations of ethyl dodecanoate, ethyl decanoate, and ethyl octanoate. Subsequently, ‘Misty’ and ‘Star’, with distinct aroma profiles, were selected to further unravel the impact of berry size on blueberry wine aroma. The findings revealed that small berries significantly enhanced ‘Misty’ blueberry wines, increasing higher alcohol, ester, and terpenoid content, resulting in a more intense fruity and floral aroma. Interestingly, berry size had no discernible influence on ‘Star’ blueberry wine aroma. This study provides valuable insights into the enhancement of blueberry wine production, shedding light on the intricate interplay of cultivar selection, berry sorting, and their impact on the aromatic attributes of the final product.