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Abstract Objective This study aims to explore the effect of an extract of Atractylodes lancea (A. lancea) on antibiotics-induced intestinal tract disorder and the probable therapeutic mechanisms employed by this extract to ameliorate these disorders. Methods Three days after acclimatization, nine male and nine female specific-pathogen-free (SPF) mice were randomly assigned into three groups: Group C (normal saline), Group M (antibiotic: cefradine + gentamicin), and Group T (antibiotic + A. lancea extract). Each mouse in Groups M and T received intragastric (i.g.) gavage antibiotics containing cefradine and gentamicin sulfate (0.02 ml/g−1/D−1) for 7 days. A. lancea extract (0.02 ml/g−1/D−1) was administered by i.g. gavage to Group T mice for 7 days following the cessation of antibiotic therapy. Group M received an equivalent volume of normal saline for 7 days, while Group C received an equivalent volume of normal saline for 14 days. Afterwards, we collected mouse feces to assess changes in intestinal microbiota by 16S ribosomal ribonucleic acid (rRNA) sequencing and metabolomics. In addition, serum samples were gathered and analyzed using liquid chromatography–mass spectrometry (LS-MS). Finally, we performed a correlation analysis between intestinal microbiota and metabolites. Results After treatment with antibiotic, the richness and diversity of the flora, numbers of wall-breaking bacteria and Bacteroidetes, and the numbers of beneficial bacteria decreased, while the numbers of harmful bacteria increased. After i.g. administration of A. lancea extract, the imbalance of microbial flora began to recover. Antibiotics primarily influence the metabolism of lipids, steroids, peptides, organic acids, and carbohydrates, with lipid compounds ranking first. Arachidonic acid (AA), arginine, and proline have relatively strong effects on the metabolisms of antibiotic-stressed mice. Our findings revealed that A. lancea extract might restore the metabolism of AA and L-methionine. The content of differential metabolites detected in the serum of Group T mice was comparable to that in the serum of Group C mice, but significantly different from that of Group M mice. Compared to putative biomarkers in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, it was found that altered metabolites, such as amino acids, glycerol, and phospholipids, were primarily associated with the metabolism. Conclusions The effective mechanisms of A. lancea extract in regulating the disorder of intestinal flora in mice are related to the mechanisms of A. lancea. It could relate to lipid metabolism, bile acid metabolism, and amino acid metabolism. These results will provide a basis for further explaining the mechanism by which A. lancea regulats intestinal flora.

The presence of measurable residual disease (MRD) is strongly associated with treatment outcomes in acute myeloid leukemia (AML). Despite the correlation with clinical outcomes, MRD assessment has yet to be standardized or routinely incorporated into clinical trials and discrepancies have been observed between different techniques for MRD assessment. In 62 patients with AML, aged 18-60 years, in first complete remission after intensive induction therapy on the randomized phase III SWOG-S0106 clinical trial (clinicaltrials gov. Identifier: NCT00085709), MRD detection by centralized, high-quality multiparametric flow cytometry was compared with a 29-gene panel utilizing duplex sequencing (DS), an ultrasensitive next-generation sequencing method that generates double-stranded consensus sequences to reduce false positive errors. MRD as defined by DS was observed in 22 (35%) patients and was strongly associated with higher rates of relapse (68% vs. 13%; hazard ratio [HR] =8.8; 95% confidence interval [CI]: 3.2-24.5; P

Summary: Paneth cells (PC) play a key role in the innate immune response of intestine epithelium, and PC defects contribute to the pathogenesis of Crohn’s disease (CD). In this study, we utilized active CD tissues and advanced oxidation protein products (AOPP)-challenged C57BL/6 mouse model to investigate the effect of AOPP on PC defects in CD. We found that AOPP accumulated in active CD tissues and was negatively associated with lysozyme expression, while positively correlated with the presence of ER stress markers. Furthermore, AOPP treatment induced PC defects mainly through excessive ER stress in vivo, and AOPP also caused mitochondria-associated ER membranes formation and mitochondrial dysfunction. In addition, the effects of AOPP could be attenuated by the administration of ER stress inhibitor, TUDCA. These findings suggest a pathogenic role of AOPP contributing to PC defects and may provide the basis for developing new strategies to managing CD.

Abstract Background Hepatocellular carcinoma is one of the most common and deadly cancers. The aim of this study was to elucidate the role of tRNA methyltransferase 6 (TRMT6) during HCC progression. Methods The role of TRMT6 in the progression and prognosis of HCC was confirmed by analysis of online databases and clinical human samples. The effects of up-regulation or down-regulation of TRMT6 on HCC cell proliferation and PI3K/AKT pathway-related protein expressions were verified. The molecular mechanism was investigated in vivo by constructing subcutaneous xenograft tumor model. Results TRMT6 was overexpressed in HCC tissues and associated with Tumour-Node-Metastasis (TNM) stage, primary tumor (T) and regional lymph node (N) classification. TRMT6 expressions in HCC cell lines were higher than that in normal liver cell. TRMT6 overexpression can promote HCC cell proliferation, increase the number of S phase cells. Interference with TRMT6 reduced the PI3K/AKT pathway-related protein expressions, and was reversed by the addition of IGF1. Interference with TRMT6 inhibited tumor growth in vivo and was related to PI3K/AKT pathway. Conclusions Overexpression of TRMT6 promote HCC cell proliferation in vivo and in vitro through PI3K/AKT/mTOR axis, which provides a potential choice for the treatment of HCC in clinical practice.

Teflon, polytetrafluorethylene (PTFE), is an important material in bioscience and medical application due to its special characteristics (bio-compatible, nonflammable, antiadhesive, and heat resistant). The advantages of ultrashort laser processing of Teflon include a minimal thermal penetration region and low processing temperatures, precision removal of material, and good-quality feature definition. In this paper, laser processing of PTFE in ambient air by a Ti:sapphire femtosecond laser (780 nm, 110 fs) is investigated. It is found that the pulse number on each irradiated surface area must be large enough for a clear edge definition and the ablated depth increases with the pulse number. The air ionization effect at high laser fluences not only degrades the ablated structures quality but also reduces the ablation efficiency. High quality microstructures are demonstrated with controlling laser fluence below a critical fluence to exclude the air ionization effect. The ablated microstructures show strong adhesion property to liquids and clear edges that are suitable for bio-implantation applications. Theoretical calculation is used to analyze the evolution of the ablated width and depth at various laser fluences. [ABSTRACT FROM AUTHOR]

We report a remarkably robust phenomenon in the HCN/HNC molecule where the population of a target state induced by a resonant multiphoton (MP) π-pulse along a strongly-coupled subset of states can leak to a background state only weakly coupled to this subset. This resonance leaking of population, which may be complete, is due to the overlap of the resonant MP transition to the target state with a resonant MP transition to the background state that includes the target state as an intermediate. We also demonstrate how the population leak can be fully controlled using fields of greater complexity compared to a single π-pulse, such as two overlapping, phase-adjusted Gaussian pulses. The robustness of resonance leaking in the HCN/HNC molecule suggests that the phenomenon have a significant probability of occurrence in other molecular systems as well. The implications of our findings for the viability of reduced basis set treatments in providing converged ab initio fields and the predictability of these fields in laser-controlled molecular processes are discussed. [ABSTRACT FROM AUTHOR]

In order to further strengthen the operation protection measures of the optical cable and realize real-time monitoring of the hidden danger of external force damage in the optical cable line area, this paper uses the principle of Rayleigh backscattering and coherent detection to design and construct an optical cable external damage event monitoring based on distributed optical fiber vibration sensing early warning system. Using Phase Sensitive Optical Time Domain Reflectometer (Φ-OTDR) technology, the optical fiber vibration signal is collected in real time. The key characteristics of vibration sensing are extracted, and the type of hidden danger is sent to the operation and maintenance staff to locate and warn the hidden danger of external force damage in real time. Field verification results show that the system can simultaneously detect and locate multiple vibration sources along the sensing fiber, and can identify various types of disturbance signals. The monitoring and early warning system has a complete system and a simple structure. The recognition rate of various construction signals is as high as 95%. It realizes double early warning of the type of external breakage and precise location, which can effectively prevent and stop external damage events and improve the work efficiency of anti-external breakage of optical cables.

Rheumatoid arthritis (RA) is a type of chronic autoimmune and inflammatory disease. In the pathological process of RA, the alteration of fibroblast-like synoviocyte (FLS) and its related factors is the main influence in the clinic and fundamental research. In RA, FLS exhibits a uniquely aggressive phenotype, leading to synovial hyperplasia, destruction of the cartilage and bone, and a pro-inflammatory environment in the synovial tissue for perpetuation and progression. Evidently, it is a highly promising way to target the pathological function of FLS for new anti-RA drugs. Based on this, we summed up the pathological mechanism of RA-FLS and reviewed the recent progress of small molecule drugs, including the synthetic small molecule compounds and natural products targeting RA-FLS. In the end, there were some views for further action. Compared with MAPK and NF-κB signaling pathways, the JAK/STAT signaling pathway has great potential for research as targets. A small number of synthetic small molecule compounds have entered the clinic to treat RA and are often used in combination with other drugs. Meanwhile, most natural products are currently in the experimental stage, not the clinical trial stage, such as triptolide. There is an urgent need to unremittingly develop new agents for RA.

Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease worldwide, without any Food and Drug Administration-approved pharmacological intervention in clinic. Trim38, as an important member of the TRIM (tripartite motif-containing) family, was largely reported to be involved in the regulation of innate immune and inflammatory responses. However, the functional roles of TRIM38 in NAFLD remain largely unknown. Here, the expression of TRIM38 was first detected in liver samples of both NAFLD mice model and patients diagnosed with NAFLD. We found that TRIM38 expression was downregulated in NAFLD liver tissues compared with normal liver tissues. Genetic Trim38-KO in vivo showed that TRIM38 depletion deteriorated the high-fat diet and high fat and high cholesterol diet-induced hepatic steatosis and high fat and high cholesterol diet-induced liver inflammation and fibrosis. In particular, we found that the effects of hepatocellular lipid accumulation and inflammation induced by palmitic acid and oleic acid were aggravated by TRIM38 depletion but mitigated by TRIM38 overexpression in vitro. Mechanically, RNA-Seq analysis demonstrated that TRIM38 ameliorated nonalcoholic steatohepatitis progression by attenuating the activation of MAPK signaling pathway. We further found that TRIM38 interacted with transforming growth factor-β-activated kinase 1 binding protein 2 and promoted its protein degradation, thus inhibiting the transforming growth factor-β-activated kinase 1-MAPK signal cascades. In summary, our study revealed that TRIM38 could suppress hepatic steatosis, inflammatory, and fibrosis in NAFLD via promoting transforming growth factor-β-activated kinase 1 binding protein 2 degradation. TRIM38 could be a potential target for NAFLD treatment.

Since the first Immune Checkpoint Inhibitor was developed, tumor immunotherapy has entered a new era, and the response rate and survival rate of many cancers have also been improved. Despite the success of immune checkpoint inhibitors, resistance limits the number of patients who can achieve a lasting response, and immune-related adverse events complicate treatment. The mechanism of immune-related adverse events (irAEs) is unclear. We summarize and discuss the mechanisms of action of immune checkpoint inhibitors, the different types of immune-related adverse events and their possible mechanisms, and describe possible strategies and targets for prevention and therapeutic interventions to mitigate them.

BackgroundThis study aims to assess the prevalence of atrial cardiomyopathy (ACM) in patients with new-onset metabolic syndrome (MetS) and investigate whether ACM could be a predictor of hospital admission for cardiovascular (CV) events.MethodsPatients with MetS who were free of clinically proven atrial fibrillation and other CV diseases (CVDs) at baseline were included in the present study. The prevalence of ACM was compared between MetS patients with and without left ventricular hypertrophy (LVH). The time to first hospital admission for a CV event between subgroups was assessed using the Cox proportional hazard model.ResultsA total of 15,528 MetS patients were included in the final analysis. Overall, LVH patients accounted for 25.6% of all newly diagnosed MetS patients. ACM occurred in 52.9% of the cohort and involved 74.8% of LVH patients. Interestingly, a significant percentage of ACM patients (45.4%) experienced MetS without LVH. After 33.2 ± 20.6 months of follow-up, 7,468 (48.1%) patients had a history of readmission due to CV events. Multivariable Cox regression analysis revealed that ACM was associated with an increased risk of admission for CVDs in the MetS patients with LVH [hazard ratio (HR), 1.29; 95% confidence interval (CI), 1.142–1.458; P

The integration of advanced sensor technology and control technology has gradually improved the operational efficiency of traditional power systems. Due to the undetectability of these attacks using traditional chi-square detection techniques, the state estimation of power systems is vulnerable to cyber–physical attacks, For this reason, this paper presents a novel detection and identification framework for detecting malicious attacks in power systems from the perspective of cyber–physical symmetry. To consider the undetectability of cyber–physical attacks, a physical dynamics detection model using the unknown input observers (UIOs) and cosine similarity theorem is proposed. Through the design of UIO parameters, the influence of attacks on state estimation can be eliminated. A cosine similarity value-based detection criterion is proposed to replace the traditional detection threshold. To further cut down the effects caused by malicious attacks, an observer combination-based attack identification framework is established. Finally, simulations are given to demonstrate that the proposed security method can detect and identify the injected malicious attacks quickly and effectively.

BackgroundPathological cardiac hypertrophy is commonly resulted from sustained pressure overload and/or metabolic disorder and eventually leads to heart failure, lacking specific drugs in clinic. Here, we aimed to identify promising anti-hypertrophic drug(s) for heart failure and related metabolic disorders by using a luciferase reporter-based high-throughput screening.MethodsA screen of the FDA-approved compounds based on luciferase reporter was performed, with identified luteolin as a promising anti-hypertrophic drug. We systematically examined the therapeutic efficacy of luteolin on cardiac hypertrophy and heart failure in vitro and in vivo models. Transcriptome examination was performed to probe the molecular mechanisms of luteolin.ResultsAmong 2,570 compounds in the library, luteolin emerged as the most robust candidate against cardiomyocyte hypertrophy. Luteolin dose-dependently blocked phenylephrine-induced cardiomyocyte hypertrophy and showed extensive cardioprotective roles in cardiomyocytes as evidenced by transcriptomics. More importantly, gastric administration of luteolin effectively ameliorated pathological cardiac hypertrophy, fibrosis, metabolic disorder, and heart failure in mice. Cross analysis of large-scale transcriptomics and drug-target interacting investigations indicated that peroxisome proliferator activated receptor γ (PPARγ) was the direct target of luteolin in the setting of pathological cardiac hypertrophy and metabolic disorders. Luteolin can directly interact with PPARγ to inhibit its ubiquitination and subsequent proteasomal degradation. Furthermore, PPARγ inhibitor and PPARγ knockdown both prevented the protective effect of luteolin against phenylephrine-induced cardiomyocyte hypertrophy in vitro.ConclusionOur data clearly supported that luteolin is a promising therapeutic compound for pathological cardiac hypertrophy and heart failure by directly targeting ubiquitin-proteasomal degradation of PPARγ and the related metabolic homeostasis.

The Laguerre-Gaussian (LG) and Hermite-Gaussian (HG) modes can be interconverted with an astigmatism phase. In this paper, based on the single beam, the interconversion of LG and HG beams array with the astigmatism phase is analyzed theoretically and the spatial mapping relationship is derived. In the experiment, 1 × 3, 2 × 2, 3 × 3 LG beams arrays are generated and converted into HG beams array via employing a spatial light modulator loaded with 0°, 90°, 45°, −45° astigmatism phases. The experimental results are in great agreement with the theoretical analyses. Moreover, from the number and direction of the dark fringe of converted HG beams array, the orbital angular momentum information of LG beams array can be obtained. This work theoretically perfects the theoretical model of the interconversion between LG and HG beams based on an astigmatism phase, and also provides a theoretical support for measuring the LG beams array.

Recurrent gene fusions are common drivers of disease pathophysiology in leukemias. Identifying these structural variants helps stratify disease by risk and assists with therapy choice. Precise molecular diagnosis in low-and-middle-income countries (LMIC) is challenging given the complexity of assays, trained technical support, and the availability of reliable electricity. Current fusion detection methods require a long turnaround time (7-10 days) or advance knowledge of the genes involved in the fusions. Recent technology developments have made sequencing possible without a sophisticated molecular laboratory, potentially making molecular diagnosis accessible to remote areas and low-income settings. We describe a long-read sequencing DNA assay designed with CRISPR guides to select and enrich for recurrent leukemia fusion genes, that does not need a priori knowledge of the abnormality present. By applying rapid sequencing technology based on nanopores, we sequenced long pieces of genomic DNA and successfully detected fusion genes in cell lines and primary specimens (e.g., BCR::ABL1, PML::RARA, CBFB::MYH11, KMT2A::AFF1) using cloud-based bioinformatics workflows with novel custom fusion finder software. We detected fusion genes in 100% of cell lines with the expected breakpoints and confirmed the presence or absence of a recurrent fusion gene in 12 of 14 patient cases. With our optimized assay and cloud-based bioinformatics workflow, these assays and analyses could be performed in under 8 hours. The platform's portability, potential for adaptation to lower-cost devices, and integrated cloud analysis make this assay a candidate to be placed in settings like LMIC to bridge the need of bedside rapid molecular diagnostics.

Ganoderma lucidum (G. lucidum, Lingzhi) is a well-known herbal medicine with a variety of pharmacological effects. Studies have found that G. lucidum has pharmacological effects such as antioxidant, antitumor, anti-aging, anti-liver fibrosis, and immunomodulation. The main active components of G. lucidum include triterpenoids, polysaccharides, sterols, peptides and other bioactive components. Among them, the triterpenoids and polysaccharide components of G. lucidum have a wide range of anti-liver fibrotic effects. Currently, there have been more reviews and studies on the antioxidant, antitumor, and anti-aging properties of G. lucidum. Based on the current trend of increasing number of liver fibrosis patients in the world, we summarized the role of G.lucidum extract in anti-liver fibrosis and the effect of G. lucidum extract on liver fibrosis induced by different pathogenesis, which were discussed and analyzed. Research and development ideas and references are provided for the subsequent application of G. lucidum extracts in anti-liver fibrosis treatment.

PI3K/Akt, an essential signaling pathway widely present in cells, has been shown to be relevant to neurological disorders. As an important class of natural products, terpenoids exist in large numbers and have diverse backbones, so they have a great chance to be identified as neuroprotective agents. In this review, we described and summarized recent research for a range of terpenoid natural products associated with the PI3K/Akt pathway by classifying their basic chemical structures of the terpenes, identified by electronic searches on PubMed, Web of Science for research, and Google Scholar websites. Only articles published in English were included. Our discussion here concerned 16 natural terpenoids and their mechanisms of action, the associated diseases, and the methods of experimentation used. We also reviewed the discovery of their chemical structures and their derivatives, and some compounds have been concluded for their structure–activity relationships (SAR). As a result, terpenoids are excellent candidates for research as natural neuroprotective agents, and our content will provide a stepping stone for further research into these natural products. It may be possible for more terpenoids to serve as neuroprotective agents in the future.

IntroductionLow back pain (LBP) is the most prevalent form of chronic pain in active-duty military personnel worldwide. Electroacupuncture (EA) and neuromuscular electrical stimulation (NMES) are the two most widely used treatment methods in the military, while evidence for their benefits is lacking. The aim of this randomized clinical trial is to investigate the effectiveness of EA vs. NMES in reducing pain intensity among active-duty navy personals with chronic LBP.MethodsThe study is designed as a single-center, randomized controlled trial. The primary outcome is a positive categorical response for treatment success in the first-time follow-up, which is predesignated as a two-point or greater decrease in the NRS score and combined with a score > 3 on the treatment satisfaction scale. The secondary outcomes include pain intensity, rate of treatment success, and Oswestry Disability Index (ODI) fear-avoidance beliefs questionnaire (FABQ) score along with muscular performance. The first follow-up starts on the first day after completing the last treatment session, and then the 4-weeks and 12-weeks follow-up are applied via telephone visit.ResultsEighty-five subjects complete the treatment diagram and are included in the analysis. For the primary outcome, no difference has been found between EA and NMES, with 65.1% (28 in 43) individuals reporting a positive response to EA treatment, while 53.5% (23 in 43) in NMES. However, for longer follow-ups, superiority in positive response of EA has been found in 4-weeks (26 in 39, 66.7% vs. 16 in 40, 40%; P = 0.018) and 12-weeks (24 in 36, 66.7% vs. 12 in 36, 33.3%; P = 0.005) follow-up. In the regression analysis, baseline pain intensity and FABQ score are identified to be highly associated with positive treatment outcomes. Finally, the subgroup analysis suggests that EA treatment is associated with better long-term outcomes in patients with LBP with a severe pain score (NRS score >4, Figure 4B) and stronger fear-avoidance beliefs.ConclusionBoth the EA and NMES are associated with a positive response in treating military LBP, and the former offers lasting benefits in the later follow-ups. Thus, electroacupuncture is a more recommended treatment for military LBP. A lot of research is needed to verify an efficient and standardized treatment session, with more information and evidence about indications for these treatments.Trial registrationChiCTR, (ChiCTR2100043726); registered February 27, 2021.

Mitochondrion and ferroptosis are related to tumorigenesis and tumor progression of hepatocellular carcinoma (HCC). Therefore, this study focused on exploring the participation of lncRNAs in mitochondrial dysfunction and ferroptosis using public datasets from The Cancer Genome Atlas (TCGA) database. We identified the mitochondrion- and ferroptosis-related lncRNAs by Pearson’s analysis and lasso-Cox regression. Moreover, real-time quantitative reverse transcription PCR (RT-qPCR) was utilized to further confirm the abnormal expression of these lncRNAs. Based on eight lncRNAs, the MF-related lncRNA prognostic signature (LPS) with outstanding stratification ability and prognostic prediction capability was constructed. In addition, functional enrichment analysis and immune cell infiltration analysis were performed to explore the possible functions of lncRNAs and their impact on the tumor microenvironment. The pathways related to G2M checkpoint and MYC were activated, and the infiltration ratio of regulatory T cells and M0 and M2 macrophages was higher in the high-risk group. In conclusion, these lncRNAs may affect mitochondria functions, ferroptosis, and immune cell infiltration in HCC through specific pathways, which may provide valuable insight into the progression and therapies of HCC.

The goal of this study was to examine driver performance under different combinations of horizontal and vertical alignment in rural two-lane roads. The SHRP2 roadway information database (RID) was used to identify study sites on rural two lane roads from New York and Pennsylvania that included tangent sections, straight grades, horizontal curves, vertical curves, and combinations. The study included the development of an algorithm that used the RID to identify vertical curves. For these study sites, time series data, forward video, and eye glance data were extracted for a sample of drivers and trips from the SHRP2 Naturalistic Driving Study (NDS). The time series data included kinematics variables such as speed, acceleration, lane position, distance from left and right lane markings, and steering wheel position. The forward video provided the driver's viewpoint, and was used to record events such as presence of lead vehicle, presence of vehicle in the opposing lane, and intrusions from vehicles and other road users. The eye glance data provided information on where a driver was looking every fraction of a second. The analysis of the NDS data showed that the alignment categories that include a horizontal curve have the worst performance in terms of the lane deviation measures. In addition, sharper horizontal curves are associated with the higher absolute values of lane deviation. The analysis was conducted using both disaggregate and aggregate methods. Comparison of the CMFs from a recent study by the Federal Highway Administration [1] with the performance measures indicates a good match with the lane deviation measures, indicating that the lane deviation measures could serve as good surrogates for crash propensity. [ABSTRACT FROM AUTHOR]

Post-translational modifications of tubulins regulate microtubule properties and neural development. Here, the authors report that one such post-translational modification, α-TubK40me3, is required for neuronal polarization and migration by promoting microtubule formation.

Although epidemiological studies suggest that periodontitis is tightly associated with ischemic stroke, its impact on ischemic stroke and the underlysing mechanisms are poorly understood. Recent studies have shown that alteration in gut microbiota composition influences the outcomes of ischemic stroke. In the state of periodontitis, many oral pathogenic bacteria in the saliva are swallowed and transmitted to the gut. However, the role of periodontitis microbiota in the pathogenesis and progression of ischemic stroke is unclear. Therefore, we hypothesized that the periodontitis salivary microbiota influences the gut immune system and aggravates ischemic stroke. Mice receiving gavage of periodontitis salivary microbiota showed significantly worse stroke outcomes. And these mice also manifested more severe neuroinflammation, with higher infiltration of inflammatory cells and expression of inflammatory cytokines in the ischemic brain. More accumulation of Th17 cells and IL-17+ γδ T cells were observed in the ileum. And in Kaede transgenic mice after photoconversion. Migration of CD4+ T cells and γδ T cells from the ileum to the brain was observed after ischemic stroke in photoconverted Kaede transgenic mice. Furthermore, the worse stroke outcome was abolished in the IL-17A knockout mice. These findings suggest that periodontitis salivary microbiota increased IL-17A-producing immune cells in the gut, likely promoted the migration of these cells from the gut to the brain, and subsequently provoked neuroinflammation after ischemic stroke. These findings have revealed the role of periodontitis in ischemic stroke through the gut and provided new insights into the worse outcome of ischemic stroke coexisting with periodontitis in clinical trials.

Abstract Sharing logistics platform can effectively realize the sharing of idle logistics resources and maximize the utility of logistics resources utilization by publishing and matching the supply and demand information of logistics resource. For sharing logistics platform, subsidy strategy plays a significant role in winning market competition. Therefore, how to establish an effective subsidy scheme is a burning issue. By analyzing the problems in the transaction orders of drivers and consignor on the sharing logistics platform, this paper estimates the subsidy strategy on the following three aspects: (1) establish a dynamic model of freight supply and demand matching according to the freight cost and determine the impact of different subsidy policies on the platform usage; (2) evaluate the solution of different subsidy policies to the matching problem of vehicles and goods, and determine the optimal subsidy scheme based on the evaluation results; (3) establish the subsidy model based on platform maximum benefit and social welfare optimization and analyze a practical case of "Huochebang" (a Sharing logistics platform). The analysis results show that the model constructed in this paper can be well applied to the subsidy problem of sharing logistics platform and assist the platform to establish the most suitable subsidy policy to achieve the optimal economic benefits.

BackgroundCompared with the traditional pressurized water reactor (PWR), the core design of large advanced PWR CAP1400 has significant changes, such as the increase in the number of fuel assemblies, the increase in reactor power, the increase in the average temperature of core coolant, etc. These changes have an important impact on the results of rod ejection accident, and then affect the safety of reactor.PurposeThis study aims to verify the safety of large advanced PWR under rod ejection accident condition and the influence of key input parameters on accident analysis results.MethodsBased on the neutron dynamics software TWINKLE and fuel performance analysis program FACTRAN, the typical four types of operating conditions, including the beginning of life the hot full power and the hot zero power, the end of life the hot full power and the hot zero power, were selected to carry out the simulation calculation of the control rod ejection accident analysis for large advanced PWR, and the sensitivity analysis of key input parameters of rod ejection accident conditions was performed by using the direct numerical perturbation method.Results & ConclusionsSimulation results show that the power peak is the most sensitive to the worth of rod ejection, but less sensitive to shutdown reactivity. The consequences of the control rod ejection accident designed for CAP1400 can meet the requirements of acceptance criteria and the reactor is in the safe and controllable state.

Canine models are increasingly being used in metabolic studies due to their physiological similarity with humans. The present study aimed to identify changes in metabolic pathways and biomarkers with potential clinical utility in a canine model of obesity and metabolic disorders induced by a high-fat diet (HFD). Eighteen male beagles were included in this study, 9 of which were fed a HFD for 24 weeks, and the remaining 9 were fed normal chow (NC) during the same period. Plasma and urine samples were collected at weeks 12 and 24 for untargeted metabolomic analysis. Dogs fed a HFD showed a gradual body weight increase during the feeding period and had hyperlipidemia, increased leukocyte counts, and impaired insulin sensitivity at week 24. Plasma and urine metabonomics analysis displayed clear separations between the HFD-fed and NC-fed dogs. A total of 263 plasma metabolites varied between the two groups, including stearidonic acid, linolenic acid, carnitine, long-chain ceramide, 3-methylxanthine, and theophylline, which are mainly engaged in fatty acid metabolism, sphingolipid metabolism, and caffeine metabolism. A total of 132 urine metabolites related to HFD-induced obesity and metabolic disorders were identified, including 3-methylxanthine, theophylline, pyridoxal 5’-phosphate, and harmine, which participate in pathways such as caffeine metabolism and vitamin digestion and absorption. Eight metabolites with increased abundance (e.g., 3-methylxanthine, theophylline, and harmine) and 4 metabolites with decreased abundance (e.g., trigonelline) in both the plasma and urine of the HFD-fed dogs were identified. In conclusion, the metabolomic analysis revealed molecular events underlying a canine HFD model and identified several metabolites as potential targets for the prevention and treatment of obesity-related metabolic disorders.

Increasing evidence suggests that periodontitis, characterized by oral dysbiosis, is a critical player in the progression of multiple systemic diseases in humans. However, there is still a lack of a proper mouse model of periodontitis with the colonization of human periodontitis-associated bacteria. We here established a new mouse periodontitis model by combining ligation of the second molars with application of subgingival plaques from periodontitis patients. Using 16S rRNA gene sequencing and Taxonomic classification, we found that human periodontitis-associated bacteria efficiently colonized in the mouse model and were enriched in both ligature silk and mouse saliva. Furthermore, the well-recognized periodontal pathogens including Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia, and Tannerella forsythia were enriched in the new model, but not in ligature-induced periodontitis model or Sham mice. The human periodontitis-associated bacteria potently aggravated mouse periodontitis, as demonstrated by more severe bone resorption and higher expression of inflammatory and osteoclastogenesis genes. In summary, the new mouse periodontitis model paves the way for studying human periodontitis-associated bacteria in oral diseases and systemic diseases.