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Abstract Pityriasis rubra pilaris (PRP) is an inflammatory papulosquamous dermatosis, characterized by hyperkeratotic follicular papules and erythematous desquamative plaques. The precise pathogenic mechanism underlying PRP remains incompletely understood. Herein, we conduct a case-control study involving a cohort of 102 patients with sporadic PRP and 800 healthy controls of Han Chinese population and identify significant associations (P = 1.73 × 10−6) between PRP and heterozygous mutations in the Keratin 32 gene (KRT32). KRT32 is found to be predominantly localized in basal keratinocytes and exhibits an inhibitory effect on skin inflammation by antagonizing the NF-κB pathway. Mechanistically, KRT32 binds to NEMO, promoting excessive K48-linked polyubiquitination and NEMO degradation, which hinders IKK complex formation. Conversely, loss-of-function mutations in KRT32 among PRP patients result in NF-κB hyperactivation. Importantly, Krt32 knockout mice exhibit a PRP-like dermatitis phenotype, suggesting compromised anti-inflammatory function of keratinocytes in response to external pro-inflammatory stimuli. This study proposes a role for KRT32 in regulating inflammatory immune responses, with damaging variants in KRT32 being an important driver in PRP development. These findings offer insights into the regulation of skin immune homeostasis by keratin and open up the possibility of using KRT32 as a therapeutic target for PRP.

Refractory high-entropy alloys (RHEAs) have good overall properties and potential high temperature applications, but they are not competitive in terms of light weight and wear and corrosion resistance, which severely limits the wide range of applications. In this paper, novel NbMoZrTi-X (Al, V) light refractory high entropy alloys (LRHEAs) were fabricated and their physical phase composition, microstructure, hardness, and wear and corrosion resistance were systematically investigated. The results show that NbMoZrTi LRHEA and NbMoZrTiV LRHEA are both single BCC structures, while NbMoZrTiAl LRHEA and NbMoZrTiAlV LRHEA are transformed into BCC, B2, and Zr5Al3 phase structures. The hardness increases as the volume fraction of the Zr5Al3 hard phase increases, with NbMoZrTiAl LRHEA having a maximum Vickers hardness of 811.29 HV. Room temperature dry friction tests showed that NbMoZrTiAl LRHEA had the lowest wear and coefficient of friction of 1.5 mg and 0.6713, respectively. Electrochemical tests performed in 3.5 wt% NaCl solution showed that NbMoZrTiAlV LRHEA has excellent corrosion resistance with the highest Ecorr (−0.142 V) and the lowest Icorr (2.149 × 10−7 A/cm2). Therefore, the addition of V and Al to NbMoZrTi-based LRHEA can effectively improve its wear and corrosion resistance due to the increase in hardness and dense passivation film formation. Our study provides a new strategy for designing LRHEAs with a combination of high hardness and excellent wear and corrosion resistance.

Abstract The integration of gray and green infrastructure has proven to be a feasible approach for managing stormwater in established urban areas. However, evaluating the specific contributions of such coupled strategies is challenging. This study introduced a novel integrated hydrological-hydrodynamic model that takes into account the layout of low-impact development (LID) facilities along with pipeline alignment and rehabilitation. Reliable results from modeling were used to assess the individual contribution of LID and improved drainage facilities to urban flooding mitigation. We selected a natural island in Guangzhou City, China, as the study site. The results indicate that combining three LID measures, namely green roofs, sunken green spaces, and permeable pavements, can reduce total runoff by 41.7% to 25.89% for rainfall recurrence periods ranging from 1 year to 100 years, and decrease the volume of nodal overflow by nearly half during rainfall events of less than 10-year return period. By integrating LID measures with the upgraded gray infrastructure, the regional pipeline overloading condition is substantially alleviated, resulting in a significant improvement in pipeline system resilience. For urban flooding control, it is recommended to integrate sufficient green space and avoid pipe-laying structural issues during urban planning and construction. The findings may assist stakeholders in developing strategies to best utilize gray and green infrastructure in mitigating the negative effects of urban flooding.

Pollution in wetland flows poses a significant challenge to ecosystem preservation, underscoring the importance of wetland restoration. Constructed wetlands have emerged as a widely embraced solution for contaminant mitigation. In this study, we focus on the contaminant removal process within the wetland flows to contribute to wetland restoration. A constructed wetland with ecological floating and bottom absorptive beds has been employed to enhance the capacity of contaminant removal within wetland flows. However, the environmental dispersion in constructed wetland flows is further complicated by the presence of irreversible first-order absorptive boundaries at the upper and bottom beds. Therefore, our work focuses on comprehending the expansion processes of contaminant clouds under absorptive boundaries through a multiscale analysis to demonstrate the removal effects of constructed wetlands. The findings highlight significant deviations in the spatial distribution of contaminant clouds, particularly in the vertical dimension, attributed to absorptive effects. To analyze the impact of removal mechanisms on the dispersion patterns of contaminant clouds, variations in the vertical concentration peak are examined. A predictive model is developed to estimate the position of the concentration crest in the vertical direction based on changes in absorptive ratios between the upper and bottom boundaries. Furthermore, in order to explore the key factor on removal capacity and efficiency within constructed wetland flows, we look into the process of contaminant depletion by examining variations in removed mass and local absorptive and removal efficiency along the streamwise direction in response to deviations in absorptive strengths at the upper and bottom beds. The ratios of the two boundary removal intensities play a significant role in the absorptive dynamics within wetland flows, particularly during the early stages of cloud expansion. By adjusting the absorption ratio between two absorptive beds to 1:1 with a certain total depletion strength in wetland flows, the enhancement ratio of depletion efficiency can increase by nearly 30%. It has been proven that employing identical absorption strengths at two absorptive beds is an economical and efficient means to amplify the absorption efforts within designed constructed wetland flows. This study provides guidelines for the design of constructed wetlands aimed at enhancing their capacity for sewage treatment.

Abstract Objective To identify the distinct profiles of work alienation among Chinese nurses, examine the demographic factors associated with profile memberships, and then explore the relationship between latent categories of work alienation and job embeddedness. Methods A cross-sectional survey of 523 nurses was conducted from July to August 2023. Latent profile analysis (LPA) was performed to identify distinct profiles of nurses based on three aspects: powerlessness, helplessness, and meaningfulness. A multinomial logistic regression analysis was conducted to explore the predictors of profile membership. Hierarchical regression analysis was carried out to examine the association between profile memberships and job embeddedness. Results Three subgroups of work alienation of nurses were identified: 23.1%, 57.8%, and 19.1% in the low work alienation group (profile 1), the moderate work alienation group (profile 3), and the high work alienation group (profile 2), respectively. Nurses with college degrees were more likely to be grouped into moderate work alienation. Nurses who did not work night shifts were more likely to have low or moderate levels of work alienation. Nurses earning 2,000–3,000 and 3,001–5,000 yuan per month were likely to be in the low work alienation group. The different categories of work alienation significantly predicted job embeddedness among nurses (ΔR 2 = 0.103, p

Abstract Objective Clinical approaches to analgesia following total shoulder arthroplasty include liposomal bupivacaine, local infiltration analgesia, single-shot interscalene block, and continuous interscalene block. However, the best method remains contentious. This study conducts a network meta-analysis comparing these four methods, aiming to identify the most effective analgesic approach. Methods Randomized controlled trials on analgesic regimens for total shoulder arthroplasty were identified through searches of PUBMED, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, and Scopus databases, covering their inception through November 2023. Network meta-analysis was performed using STATA 15.1, and the Cochrane Handbook version 5.1.0 risk of bias tool was employed for quality assessment of the literature. Results Twelve randomized controlled trials were included, comprising 1537 patients undergoing total shoulder arthroplasty. The interventions compared were ssISB, cISB, LIA, and LB. Regarding the quality of the literature, four studies were deemed low risk, one high risk, and seven moderate risk. The network meta-analysis revealed that in terms of VAS scores in the PACU, the ssISB group was the most effective, followed by cISB and LB, with LIA being the least effective. This pattern continued in VAS scores on the first and second postoperative days. Regarding morphine consumption, the cISB group showed the most significant reduction in the PACU and on the first postoperative day, while the LIA group performed best in total postoperative morphine consumption. The shortest average hospital stay was noted in the cISB group. Conclusion The ssISB method excels in controlling early postoperative pain, particularly during the PACU stage and early postoperative period. Additionally, the cISB method is notable for reducing postoperative morphine consumption and shortening average hospital stays. While the LIA method ranks first in reducing total morphine consumption, it is weaker in pain control. The LB method is underwhelming across most assessment parameters. These findings underscore the importance of selecting appropriate analgesic strategies for different postoperative recovery phases and provide valuable insights for clinicians to optimize postoperative pain management. Furthermore, they suggest a need for future research to explore the specific application and effectiveness of these methods in varying clinical contexts.

ObjectiveExisting literature has not clearly elucidated whether SARS-CoV-2 infection increases the incidence of Parkinson’s disease or if Parkinson’s disease patients are more susceptible to the effects of SARS-CoV-2 infection. To clarify the issue, this study employs a genetic epidemiological approach to investigate the association.MethodsThis study utilizes a two-sample Mendelian randomization analysis. The primary analysis employs the inverse variance-weighted (IVW) method, supplemented by secondary analyses including MR-Egger regression, weighted median, IVW radial method, and weighted mode, to evaluate the bidirectional causal relationship between Parkinson’s disease and SARS-CoV-2 infection.ResultsIVW results showed no genetic causality between SARS-CoV-2 susceptibility, hospitalization rate and severity and Parkinson’s disease. (IVW method: p = 0.408 OR = 1.10 95% CI: 0.87 ~ 1.39; p = 0.744 OR = 1.11 95% CI: 0.94 ~ 1.09; p = 0.436 OR = 1.05 95% CI: 0.93 ~ 1.17). Parkinson’s disease was not genetically associated with susceptibility to new crown infections, hospitalization rates, and severity (IVW method: p = 0.173 OR = 1.01 95% CI: 0.99 ~ 1.03; p = 0.109 OR = 1.05 95% CI: 0.99 ~ 1.12; p = 0.209 OR = 1.03 95% CI: 0.99 ~ 1.07). MR-Egger regression, weighted median, IVW radial method, and weighted mode results are consistent with the results of the IVW method.ConclusionThis study does not support a genetic link between Parkinson’s disease and SARS-CoV-2 infection, and the association observed in previous cohort studies and observational studies may be due to other confounding factors.

Typically, parasitic capacitances exist between the ground and the solar panel terminals in grid-connected PV systems. These parasitic capacitances provide a path for a leakage current, which leads to significant safety concerns, observable and seriously hazardous harmonic orders aligned with the injected grid current, and significant safety difficulties. In this research, a robust PWM controlling method that used competently in reducing the level of the leakage current and improving the power quality of a switched-capacitor Multilevel Inverter. This technique creates developed reference signals from the main signal to generate the switching scheme for the converter circuit. Additionally, the suggested control strategy only works with a small number of carrier signals, resulting in a quick system response and a simpler controller algorithm. Likewise, this controlling approach offers a stable way to maintain a constant output voltage in the suggested converter by adjusting the switching capacitors' voltages, which is not possible with traditional control techniques. MATLAB/Simulink is used to simulate the outcomes for both the suggested control approach and the traditional Phase Disposition (PD) PWM control method whereas the leakage current component reduces to 25 % compared to the captured component with the PDPWM. The simulation and the practical results based on the dSPACE-1103 hardware are quite similar.

In modern ecological systems, the overuse and misuse of antibiotics have escalated the prevalence of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs), positioning them as emerging environmental contaminants. Notably, composting serves as a sustainable method to recycle agricultural waste into nutrient-rich fertilizer while potentially reducing ARGs and MGEs. This study conducted a 47-day composting experiment using pig manure and corn straw, supplemented with chitin and N-Acetyl-D-glucosamine, to explore the impact of these additives on the dynamics of ARGs and MGEs, and to unravel the interplay between these genetic elements and microbial communities in pig manure composting. Results showed that adding 5% chitin into composting significantly postponed thermophilic phase, yet enhanced the removal efficiency of total ARGs and MGEs by over 20% compared to the control. Additionally, the addition of N-Acetyl-D-glucosamine significantly increased the abundance of tetracycline-resistant and sulfonamide-resistant genes, as well as MGEs. High-throughput sequencing revealed that N-Acetyl-D-glucosamine enhanced bacterial α-diversity, providing diverse hosts for ARGs and MGEs. Resistance mechanisms, predominantly efflux pumps and antibiotic deactivation, played a pivotal role in shaping the resistome of composting process. Co-occurrence network analysis identified the key bacterial phyla Proteobacteria, Firmicutes, Gemmatimonadota, and Myxococcota in ARGs and MGEs transformation and dissemination. Redundancy analysis indicated that physicochemical factors, particularly the carbon-to-nitrogen ratio emerged as critical variables influencing ARGs and MGEs. The findings lay a foundation for the developing microbial regulation method to reduce the risks of ARGs in animal manure composts.

Summary: Osteoporosis has gradually become a major public health problem. Further elucidation of the pathophysiological mechanisms that induce osteoporosis and identification of more effective therapeutic targets will have important clinical significance. Experiments in vitro on bone marrow stem cells (BMSCs) subjected to osteogenic and adipogenic differentiation and in vivo on surgical bilateral ovariectomy (OVX) mouse models revealed that exosomes of vascular endothelial cells (EC-EXOs) can promote osteogenic differentiation of BMSCs and inhibit BMSC adipogenic differentiation through miR-3p-975_4191. Both miR-3p-975_4191 and curcumin can target tumor necrosis factor (TNF) and act synergistically to regulate BMSCs fate differentiation and delay the progression of osteoporosis. Our findings suggest that EC-EXOs may exert a synergistic effect with curcumin in reversing the progression of osteoporosis by targeting TNF via miR-3p-975_4191. Our study may provide therapeutic options and potential therapeutic targets for osteoporosis and thus has important clinical implications.

Background: Immunotherapy has changed the treatment landscape for lung cancer. This study aims to construct a tumor mutation-related model that combines long non-coding RNA (lncRNA) expression levels and tumor mutation levels in tumor genomes to detect the possibilities of the lncRNA signature as an indicator for predicting the prognosis and response to immunotherapy in lung adenocarcinoma (LUAD). Methods: We downloaded the tumor mutation profiles and RNA-seq expression database of LUAD from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were extracted based on the cumulative number of mutations. Cox regression analyses were used to identify the prognostic lncRNA signature, and the prognostic value of the five selected lncRNAs was validated by using survival analysis and the receiver operating characteristic (ROC) curve. We used qPCR to validate the expression of five selected lncRNAs between human lung epithelial and human lung adenocarcinoma cell lines. The ImmuCellAI, immunophenoscore (IPS) scores and Tumor Immune Dysfunction and Exclusion (TIDE) analyses were used to predict the response to immunotherapy for this mutation related lncRNA signature. Results: A total of 162 lncRNAs were detected among the differentially expressed lncRNAs between the Tumor mutational burden (TMB)-high group and the TMB-low group. Then, five lncRNAs (PLAC4, LINC01116, LINC02163, MIR223HG, FAM83A-AS1) were identified as tumor mutation-related candidates for constructing the prognostic prediction model. Kaplan‒Meier curves showed that the overall survival of the low-risk group was significantly better than that of the high-risk group, and the results of the GSE50081 set were consistent. The expression levels of PD1, PD-L1 and CTLA4 in the low-risk group were higher than those in the high-risk group. The IPS scores and TIDE scores of patients in the low-risk group were significantly higher than those in the high-risk group. Conclusion: Our findings demonstrated that the five lncRNAs (PLAC4, LINC01116, LINC02163, MIR223HG, FAM83A-AS1) were identified as candidates for constructing the tumor mutation-related model which may serve as an indicator of tumor mutation levels and have important implications for predicting the response to immunotherapy in LUAD.

NECP-SARAX is a neutronics analysis code system for advanced reactor developed by Nuclear Engineering Computational Physics Laboratory of Xi'an Jiaotong University. In past few years, improvements have been implemented in TULIP code which is the cross-section generation module of NECP-SARAX, including the treatment of resonance interface, considering the self-shielding effect in non-resonance energy range, hyperfine group method and nuclear library with thermal scattering law. Previous studies show that NECP-SARAX has high performance in both fast and thermal spectrum system analysis. The accuracy of TULIP code in fast and thermal spectrum system analysis is demonstrated preliminarily. However, a systematic verification and validation is still necessary. In order to validate the applicability of TULIP code for full energy range, 147 fast spectrum critical experiment benchmarks and 170 thermal spectrum critical experiment benchmarks were selected from ICSBEP and used for analysis. The keff bias between TULIP code and reference value is less than 300 pcm for all fast spectrum benchmarks. And that bias keeps within 200 pcm for thermal spectrum benchmarks with neutron-moderating materials such as polyethylene, beryllium oxide, etc. The numerical results indicate that TULIP code has good performance for the analysis of fast and thermal spectrum system.

Abstract Current research has demonstrated that extracellular vesicles (EVs) and circulating tumor cells (CTCs) are very closely related in the process of distant tumor metastasis. Primary tumors are shed and released into the bloodstream to form CTCs that are referred to as seeds to colonize and grow in soil-like distant target organs, while EVs of tumor and nontumor origin act as fertilizers in the process of tumor metastasis. There is no previous text that provides a comprehensive review of the role of EVs on CTCs during tumor metastasis. In this paper, we reviewed the mechanisms of EVs on CTCs during tumor metastasis, including the ability of EVs to enhance the shedding of CTCs, protect CTCs in circulation and determine the direction of CTC metastasis, thus affecting the distant metastasis of tumors.

Abstract A series of carbon nitride (CN) materials represented by graphitic carbon nitride (g‐C3N4) have been widely used in bioimaging, biosensing, and other fields in recent years due to their nontoxicity, low cost, and high luminescent quantum efficiency. What is more attractive is that the luminescent properties such as wavelength and intensity can be regulated by controlling the structure at the molecular level. Hence, it is time to summarize the related research on CN structural evolution and make a prospect on future developments. In this review, we first summarize the research history and multiple structural evolution of CN. Then, the progress of improving the luminescence performance of CN through structural evolution was discussed. Significantly, the relationship between CN structure evolution and energy conversion in the forms of photoluminescence, chemiluminescence, and electrochemiluminescence was reviewed. Finally, key challenges and opportunities such as nanoscale dispersion strategy, luminous efficiency improving methods, standardization evaluation, and macroscopic preparation of CN are highlighted.

Background: Depression is associated with lowered mood, anxiety, anhedonia, cognitive impairments, and even suicidal tendencies in severe cases. Yet few studies have directed acupuncture's mechanism toward enhancing axonal repair correlated with synaptic plasticity and anti-inflammatory effects related to oxidative stress in the hippocampus. Methods: Male Sprague-Dawley (SD) rats were randomly divided into control group (CON), chronic unpredictable mild stress (CUMS) group, CUMS + electroacupuncture group (EA), and CUMS + fluoxetine group (FLX) (n = 10/group). Rats were given a 28-day treatment at the Shangxing (GV23) and Fengfu (GV16) acupoints with electroacupuncture or fluoxetine (2.1 mg/kg). Results: Rats exposed to CUMS induced depression-like behaviors and spatial learning-memory impairment, changed the ionized calcium binding adaptor molecule 1 (IBA-1), Vglut1, myelin basic protein (MBP), and postsynaptic density protein 95 (PSD95) level of hippocampal, increased the Nod-like receptor protein 3 (NLRP3), atypical squamous cell (ASC), Caspase level and hippocampal reactive oxygen species (ROS), and prompted the activation of Epha4-mediated signaling and an inflammatory response. Conversely, electroacupuncture administration reduced these changes and prevented depression-like behaviors and cognitive impairment. Electroacupuncture also promoted hippocampal expression of Sirtuin1(SIRT1), Nuclear factor erythroid 2-like (Nrf2), Heme oxygenase-1 (HO-1); reduced the expression of interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-α); and prevented neural damage, particularly the synaptic myelin sheath, and neuroinflammation by regulating Eph receptor A4 (EphA4) in the hippocampal. Conclusion: These results indicate that electroacupuncture prevents depression-like behaviors with cognitive impairment and synaptic and neuronal damage, probably by reducing EphA4, which mediates ROS hyperfunction and the inflammatory response.

Documenting the joint probability of meteorological-hydrological, meteorological-agricultural, and hydrological-agricultural drought can be invaluable for understanding drought evolution under climate change in a high-diversity watershed of south China. Through constructing the edge and joint distribution functions of multi drought indices (SPEI, SPI, SSI, and SWI) based on SWAT and copula methods, we explored the evolution of multi droughts under climate change in the East River basin. During 1997–2017 and 2023–2099, we used logistic, generalized pareto, and normal distributions to construct edge distribution functions of SPEI, SPI, SWI, and SSI. For the four indices, the probability of slight drought increased with rcp2.6, 4.5, 6.0, and 8.5, and it was higher than moderate drought. Also, Clayton, Frank, Gumbel, and Gaussian copula functions were used to construct joint distribution functions of SPEI and SSI, SPEI and SWI, SSI and SWI to quantify their interactions. During 1997–2017, the probability of slight drought was 26.15 to 41.06 %, and the return period changed from 3.8 to 2.4 years. The joint probability of meteorological-hydrological, meteorological-agricultural, and hydrological-agricultural drought in slightly was 24.4 to 31.32 %, 14.95 to 22.63 %, and 6.18 to 22.05 %, respectively. During 2023–2099, the joint probability of droughts in moderately was 3.76 to 14.19 %, and the return period was 7 to 26.6 years. Our results provide a quantitative assessment of single and joint probability of meteorological, hydrological and agricultural drought, which could be used to support watershed water resource management.

Abstract Due to its unclear etiology, there is no specific medicine to cure the recurrent and incurable inflammatory bowel disease (IBD). Unhealthy dietary habits unconsciously contributed to the progression of IBD, for example a High-Salt-Diet (HSD) is the most neglected and frequently adopted habit. However, the molecular mechanism of how HSD aggravates the progression of IBD has yet to remain uncovered. Herein, we focus on the hypothesis that necroptosis pathway may be involved in the process of IBD exacerbated by HSD. To this end, different gene expression (DEGs) profiles of human epithelia under hypertonic culture conditions were applied to screen candidate pathways. What’s more, gene expression manipulation, immune microenvironment detection, RIPK3/MLKL gene knockout (KO), and wild-type (WT) mice were carried out to research the promotion of IBD progression under treatments of high salt intake. Based on our present results, gene expression profiles in human normal colon epithelia cell NCM460 were significantly changed under salt- or sucrose-induced hypertonic culture conditions. RIPK3 was significantly up-regulated under both conditions. Furthermore, mice colon epithelia cell CT26 growth was inhibited in a time- and dose-dependent manner by extra NaCl incubation. Autophagy, and Necroptosis pathways were activated and enhanced by LPS pretreatment. HSD significantly exacerbated DSS-induced IBD symptoms in vivo in a dose-dependent manner. Moreover, RIPK3-/- and MLKL-/- mice presented severe IBD symptoms in vivo. Overall, the results demonstrated that HSD aggravated the IBD progression via necroptosis activation, providing novel strategies and promising targets for the clinical treatment of IBD.

The distribution of adipose tissue in the lungs is intricately linked to a variety of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Accurate detection and quantitative analysis of subcutaneous and visceral adipose tissue surrounding the lungs are essential for effectively diagnosing and managing these diseases. However, there remains a noticeable scarcity of studies focusing on adipose tissue within the lungs on a global scale. Thus, this paper introduces a ConvBiGRU model for localizing lung slices and a multi-module UNet-based model for segmenting subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), contributing to the analysis of lung adipose tissue and the auxiliary diagnosis of lung diseases. In this study, we propose a bidirectional gated recurrent unit (BiGRU) structure for precise lung slice localization and a modified multi-module UNet model for accurate SAT and VAT segmentations, incorporating an additive weight penalty term for model refinement. For segmentation, we integrate attention, competition, and multi-resolution mechanisms within the UNet architecture to optimize performance and conduct a comparative analysis of its impact on SAT and VAT. The proposed model achieves satisfactory results across multiple performance metrics, including the Dice Score (92.0% for SAT and 82.7% for VAT), F1 Score (82.2% for SAT and 78.8% for VAT), Precision (96.7% for SAT and 78.9% for VAT), and Recall (75.8% for SAT and 79.1% for VAT). Overall, the proposed localization and segmentation framework exhibits high accuracy and reliability, validating its potential application in computer-aided diagnosis (CAD) for medical tasks in this domain.

Abstract Background Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disease characterized by lymphocyte infiltration that destroys thyrocyte cells. The aim of the present study was to elucidate the role and mechanisms of tissue small extracellular vesicle (sEV) microRNAs (miRNAs) in the pathogenesis of HT. Methods Differentially expressed tissue sEV miRNAs were identified between HT tissue and normal tissue by RNA sequencing in the testing set (n = 20). Subsequently, using quantitative real-time polymerase chain reaction (qRT‒PCR) assays and logistic regression analysis in the validation set (n = 60), the most relevant tissue sEV miRNAs to HT were verified. The parental and recipient cells of that tissue sEV miRNA were then explored. In vitro and in vivo experiments were further performed to elucidate the function and potential mechanisms of sEV miRNAs that contribute to the development of HT. Results We identified that miR-142-3p encapsulated in T lymphocyte-derived tissue sEVs can induce Treg function defect and thyrocyte destruction through an intact response loop. Inactivation of miR-142-3p can effectively protect non-obese diabetic (NOD).H-2h4 mice from HT development display reduced lymphocyte infiltration, lower antibody titers, and higher Treg cells. Looking at the mechanisms underlying sEV action on thyrocyte destruction, we found that the strong deleterious effect mediated by tissue sEV miR-142-3p is due to its ability to block the activation of the ERK1/2 signaling pathway by downregulating RAC1. Conclusions Our findings highlight the fact that tissue sEV-mediated miR-142-3p transfer can serve as a communication mode between T lymphocytes and thyrocyte cells in HT, favoring the progression of HT.

Plant respiratory burst oxidase homologs (RBOHs) are key enzymes regulating superoxide production, which is important for plant development and responses to biotic and abiotic stresses. This study aimed to characterize the RBOH gene family in pea (Pisum sativum L.). Seven PsRBOH genes were identified in the pea genome and were phylogenetically clustered into five groups. Collinearity analyses of the RBOHs identified four pairs of orthologs between pea and soybean. The gene structure analysis showed that the number of exons ranged from 6 to 16. Amino acid sequence alignment, conserved domain, and conserved motif analyses showed that all seven PsRBOHs had typical features of plant RBOHs. The expression patterns of PsRBOH genes in different tissues provided suggested their roles in plant growth and organ development. In addition, the expression levels of PsRBOH genes under different abiotic stresses were analyzed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results demonstrated that PsRBOH genes exhibited unique stress-response characteristics, which allowed for functional diversity in response to different abiotic stresses. Furthermore, four PsRBOHs had a high probability of localization in the plasma membrane, and PsRBOH6 was localized to the plasma membrane and endoplasmic reticulum. The results of this study provide valuable information for further functional analysis of pea RBOH genes and their role in plant adaptation to climate-driven environmental constraints.

Significant advancements in Earth Observation (EO) technologies, encompassing global remote sensing and environment sensor networks, have greatly progressed the field of earth science. The management of EO sensors is crucial in collecting effective and changing EO data in real-time. Over the past few decades, Sensor Management (SM) and Multi-Sensor Management (MSM) have been extensively applied to EO research and reviewed in previous studies. The demands for EO have become highly complex with the advent of the EO sensor web era, necessitating Multi-Sensor Integration Management (MSIM), which is an advanced development of MSM. The concept of MSIM and its methods have been discussed worldwide, and the prototypes have exhibited remarkable potential for EO applications. However, MSIM is yet to be reviewed for a long time. This work provides a detailed overview of the emergence of MSIM and specifies its four key methods. This work also examines the typical MSIM prototypes and applications in EO. Then, this work identifies four future directions of MSIM in EO research. This review concludes that MSIM has emerged as a novel and indispensable sensor management paradigm set to play a significant role in the advancement of earth science research and practical applications in the future.

ABSTRACTSalmonella is a major cause of food poisoning, and its infection and antimicrobial resistance vary regionally due to different sanitary standards and the use of antimicrobials. The aim of this study is to evaluate the microbiological contamination and antimicrobial resistance of Salmonella in Shanghai, providing references for supervision over food safety and clinical treatment. This study analysed the distribution of serotypes, the distribution of antimicrobial resistance in different poultry meats and serotype of Salmonella, the correlation between different antimicrobial resistance, and multiple drug resistance (MDR) of 139 strains of Salmonella from poultry meats. The results showed that the proportion of Salmonella detected in pigeons was high, which could cause severe diseases to humans. The most common resistance was observed to TET (about 60%), and resistance was even found to IPM. Resistance to two or more antimicrobials was accounted for 75.5%, indicating a wide spreading MDR.

Bioremediation can be effective method for achieving polycyclic aromatic hydrocarbons (PAHs) degradation in soil contaminated with petroleum. The aim of this study was to compare the effect of Rhodococcus bioaugmentation (BIOE) and biostimulation (BIOS) on dibenzothiophene biodegradation and bacterial community interaction in petroleum-contaminated soils. The findings revealed that compared to natural degradation treatment (NAT) and BIOS, BIOE had the highest dibenzothiophene (DBT) and the majority of DBT degradation occurred within the first 30 days. BIOS had a positive impact in the early stage but an opposite effect in the later stages for degrading DBT. Beta diversity analysis revealed significant differences of bacterial composition among NAT, BIOS, and BIOE. Sequencing results indicated that Bacillus and Paenibacillus were dominant genera involved in DBT degradation. Network analysis revealed co-occurrence patterns and connectivity, with BIOE exhibiting higher connectivity and the highest number of links in BIOS. In summary, Rhodococcus bioaugmentation was the simplest and effective method to enhance the clustering degree of bacterial network and DBT degradation in petroleum-contaminated soil, compared to NAT and BIOS.

Drought is among the most common abiotic constraints of crop growth, development, and productivity. Integrating different omics approaches offers a possibility for deciphering the metabolic pathways and fundamental mechanisms involved in abiotic stress tolerance. Here, we explored the transcriptional and post-transcriptional changes in drought-stressed tomato plants using transcriptomic and proteomic profiles to determine the molecular dynamics of tomato drought stress responses. We identified 22467 genes and 5507 proteins, among which the expression of 3765 genes and 294 proteins was significantly changed under drought stress. Furthermore, the differentially expressed genes (DEGs) and differentially abundant proteins (DAPs) showed a good correlation (0.743). The results indicated that integrating different omics approaches is promising in exploring the multilayered regulatory mechanisms of plant drought resistance. Gene ontology (GO) and pathway analysis identified several GO terms and pathways related to stress resistance, including response to stress, abiotic stimulus, and oxidative stress. The plant hormone abscisic acid (ABA) plays pivotal roles in response to drought stress, ABA-response element binding factor (AREB) is a key positive regulator of ABA signaling. Moreover, our analysis indicated that drought stress increased the abscisic acid (ABA) content, which activated AREB1 expression to regulate the expression of TAS14, GSH-Px-1, and Hsp, ultimately improving tomato drought resistance. In addition, the yeast one-hybrid assay demonstrated that the AREB1 could bind the Hsp promoter to activate Hsp expression. Thus, this study involved a full-scale analysis of gene and protein expression in drought-stressed tomato, deepening the understanding of the regulatory mechanisms of the essential drought-tolerance genes in tomato.

Abstract Influences of photosynthesis of leaf and silique on seeds yield and quality of oilseed rape (Brassica napus L.) were explored in this study. A field comparing experiment with several rapeseed varieties was conducted and the results showed, that the leaf area index (LAI), silique surface area index (SAI), siliques number per plant, and biological yield were statistically classified as the first principal factors which greatly influenced seeds yield, the leaf net photosynthetic rate (P n) and silique P n were the second principal factors; the stomatal conductance (G s) and chlorophyll a (Chl a) content were the first principal factors which influenced leaf P n and silique P n. A shading experiment was conducted and the results showed that, under treatments of the ZH1, ZH2, and ZH3 (shading rapeseed plants during flowering stage, during time from initial flowering until seeds ripening, and during time from flowering ending until seeds ripening, respectively), respectively the seeds yield per plant was reduced by 34.6%, 84.3%, and 86.1%, the seed protein content was significantly increased. The treatment ZH1 Not, but the ZH2 and ZH3 caused significant decrease in both seed oil content and oleic acid (C18:1) content in seed oil, and the contents of linoleic acid (C18:2), linolenic acid (C18:3) in oil were significantly increased, gene expression of the ACCase (Acetyl-CoA carboxylase), FAD2 (fatty acid desaturase), and FAD3 (ω-3 fatty acid dehydrogenase) in green seeds was restrained/changed. Thus the LAI, SAI, siliques number per plant, biological yield per plant, leaf P n, silique P n, and the G s, Chl a content of leaf and silique formed an indexes system to be used in screening rapeseed variety with higher light efficiency and seeds yield; the silique photosynthesis inhibition and the photosynthates deficiency in rapeseed plant after flowering stage predominately influenced seeds yield and quality.

Abstract Background Intrauterine adhesion (IUA) is a frequent acquired endometrial condition, for which there is no effective preventive or treatment. Previous studies have found that vaginal microbiota dysregulation is closely related to endometrial fibrosis and IUA. Therefore, we wondered whether restoration of vaginal microbiota by vaginal administration of L. crispatus could prevent endometrial fibrosis and ameliorate IUA. Results First, we created a mechanically injured mouse model of IUA and restored the mice’s vaginal microbiota by the addition of L. crispatus convolvulus. The observations suggested that intrauterine injections of L. crispatus significantly decreased the degree of uterine fibrosis, the levels of IL-1β and TNF-α in blood, and downregulated the TGF-β1/SMADs signaling pathway in IUA mice. A therapy with L. crispatus considerably raised the abundance of the helpful bacteria Lactobacillus and Oscillospira and restored the balance of the vaginal microbiota in IUA mice, according to high-throughput sequencing. Then we conducted a randomized controlled trial to compare the therapeutic effect of L. crispatus with estrogen after transcervical resection of adhesion (TCRA). And the results showed that vaginal probiotics had a better potential to prevent intrauterine adhesion than estrogen. Conclusions This study confirmed that L. crispatus could restore vaginal microbiota after intrauterine surgery, inhibit endometrial fibrosis, and finally play a preventive and therapeutic role in IUA. At the same time, it is a new exploration for the treatment of gynecological diseases with vaginal probiotics. Clinical trial registration : http://www.chictr.org.cn/ , identifier (ChiCTR1900022522), registration time: 15/04/2019.

Abstract Background The importance of multidisciplinary team (MDT) centred on pregnant women with pulmonary hypertension (PH) has been highlighted. However, rare studies have explored its effects on pregnancy outcomes. This study seeks to investigate whether and how the MDT has an effect on the treatment and outcomes of PH pregnant women. Methods A pre- and post-intervention study was conducted based on an interrupted time series design to compare the treatment and outcomes of patients with PH before (pre-MDT) and after (post-MDT) implementation of the MDT. PH was defined as pulmonary artery systolic pressure (sPAP) ≥ 35 mmHg measured by echocardiography or right heart catheterization and sPAP at 35–60 mmHg and over 60 mmHg was defined as mild and severe PH, respectively. All results were analyzed by T-tests, Chi square tests or Fisher exact test and two-sided p value

The electrified hybrid shipboard power system with high-level integration of renewable energy resources and energy storage system has become the new trend for the all-electric ship (AES) configuration. However, the traditional rule-based energy management system (EMS) is not able to fulfill the increasingly complex control requirements, and a more advanced EMS control algorithm is required to handle the multiple power sources and even achieve optimal energy management control. This paper proposes a supervisory-level EMS with an improved adaptive model predictive control (AMPC) strategy to optimize the power split among the hybrid power sources and to reduce the total cost of ownership (TCO) of vessel operation, which considers not only the fuel and emission costs but also the power source degradation. In order to achieve real-time implementation, the AMPC-based EMS software has been developed and deployed to a programmable logic controller (PLC) hardware. The prototyping controller verification tests have been performed with a hybrid fuel cell-fed shipboard power system hardware-in-the-loop (HIL) plant in the lab environment. Three typical tugboat load profiles with power fluctuations are implemented as case studies. Lastly, a cost study was performed to compute the economic benefits for a ten-year long-term vessel operational cycle. The proposed AMPC-based EMS is robust and effective, which can achieve up to 12.19% TCO savings compared to those of a traditional rule-based control strategy.

The quality and safety of edible vegetable oils are closely related to human life and health, meaning it is of great significance to explore the rapid detection methods of pesticide residues in edible vegetable oils. This study explored the applicability potential of substrate-assisted laser-induced breakdown spectroscopy (LIBS) for quantitatively determining fenthion in soybean oils. First, we explored the impact of laser energy, delay time, and average oil film thickness on the spectral signals to identify the best experimental parameters. Afterward, we quantitatively analyzed soybean oil samples using these optimized conditions and developed a full-spectrum extreme learning machine (ELM) model. The model achieved a prediction correlation coefficient (RP2) of 0.8417, a root mean square error of prediction (RMSEP) of 167.2986, and a mean absolute percentage error of prediction (MAPEP) of 26.46%. In order to enhance the prediction performance of the model, a modeling method using the Boruta algorithm combined with the ELM was proposed. The Boruta algorithm was employed to identify the feature variables that exhibit a strong correlation with the fenthion content. These selected variables were utilized as inputs for the ELM model, with the RP2, RMSEP, and MAPEP of Boruta-ELM being 0.9631, 71.4423, and 10.06%, respectively. Then, the genetic algorithm (GA) was used to optimize the parameters of the Boruta-ELM model, with the RP2, RMSEP, and MAPEP of GA-Boruta-ELM being 0.9962, 11.005, and 1.66%, respectively. The findings demonstrate that the GA-Boruta-ELM model exhibits excellent prediction capability and effectively predicts the fenthion contents in soybean oil samples. It will be valuable for the LIBS quantitative detection and analysis of pesticide residues in edible vegetable oils.

This paper proposes a hybrid control scheme that combines fractional-order sliding-mode control (FOSMC) with radial basis function neural network adaptive damping passivity-based control (RBFPBC) for modular multilevel converters (MMC) under non-ideal operating conditions. According to the passive control theory, we establish the Euler–Lagrange (EL) models of positive and negative sequences based on the unbalanced grid. A passivity-based controller that satisfies the energy dissipation law is designed. To enable rapid convergence of the system energy storage function, a radial basis function neural network (RBFNN) is introduced to adjust the injection damping adaptively. Additionally, a fractional-order sliding-mode controller (FOSMC) is designed. The fractional-order sliding mode surface used can improve tracking performance, and effectively suppressed the undesirable chattering phenomenon compared to the traditional sliding-mode control (SMC). Finally, combining the two control methods can effectively solve the issue of passivity-based control (PBC) being too dependent on parameters. The proposed hybrid control scheme enhances the ability of the system to resist disturbances, and improves its overall robustness. Simulation results demonstrate the feasibility and effectiveness of this control method.

Abstract Considerable evidence suggests that insulin resistance is closely linked to Parkinson's disease (PD), leading to agents aiming at treating diabetes can be regarded as new neuroprotective strategies in PD, notably glucagon‐like peptide‐1 (GLP‐1). However, the extremely short half‐life of GLP‐1 due to degradation by the ubiquitous proteolytic enzyme limits its clinical application. In this study, we engineered the recombinant integrant probiotic strain Escherichia coli Nissle 1917 (EcN) to create a strain EcN‐GLP‐1 that effectively delivers the heterologous GLP‐1 molecule. Subsequently, we assessed its neuroprotective effects on 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP)‐induced PD mice. We demonstrated that EcN‐GLP‐1 treatment could improve motor deficits, increase tyrosine hydroxylase‐positive neurons, suppress microglia and astrocyte activation, reduce brain and colon inflammation, and ameliorate colonic barrier function damaged by MPTP induction. Meanwhile, we confirmed that the oral administration of EcN‐GLP‐1 could restore the disturbance of gut microbiota in the MPTP‐induced PD mice, by reducing the relative abundances of Akkermansia and Oscillospira, and increasing the level of Prevotella in the gut. These results support further development of an engineered probiotic platform in which production of GLP‐1 for gut‐brain disorders, such as PD.

Background: Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease that negatively impacts quality of life, exercise capacity, and mortality. This study sought to investigate the relationship between serum uric acid (UA) level and the disease severity and treatment response of patients with PAH and congenital heart disease (PAH-CHD).Methods: This study included 225 CHD patients and 40 healthy subjects. Serum UA was measured in all patients, and UA levels and haemodynamic parameters were re-evaluated in 20 patients who had received PAH-specific drug treatment for at least 7 ± 1 month.Results: Serum UA levels were significantly higher in PAH-CHD patients than in CHD patients with a normal pulmonary artery pressure and normal subjects (347.7 ± 105.7 μmol/L vs. 278.3 ± 84.6 μmol/L; 347.7 ± 105.7 μmol/L vs. 255.7 ± 44.5 μmol/L, p < 0.05). UA levels in the intermediate and high risk groups were significantly higher than those in the low-risk group (365.6 ± 107.8 μmol/L vs. 311.2 ± 82.8 μmol/L; 451.6 ± 117.6 μmol/L vs. 311.2 ± 82.8 μmol/L, p < 0.05). Serum UA levels positively correlated with mean pulmonary arterial pressure, WHO functional class, pulmonary vascular resistance, and NT-proBNP (r = 0.343, 0.357, 0.406, 0.398; p < 0.001), and negatively with mixed venous oxygen saturation (SvO2) and arterial oxygen saturation (SaO2) (r = −0.293, −0.329; p < 0.001). UA significantly decreased from 352.7 ± 97.5 to 294.4 ± 56.8 μmol/L (p = 0.001) after PAH-specific drug treatment for at least 6 months, along with significant decreases in mean pulmonary arterial pressure and pulmonary vascular resistance and increases in cardiac index and mixed SvO2.Conclusion: Serum UA can be used as a practical and economic biomarker for risk stratification and the evaluation of PAH-specific drug treatment effects for patients with PAH-CHD.

BackgroundM. leprae preferentially infects Schwann cells (SCs) in the peripheral nerves leading to nerve damage and irreversible disability. Knowledge of how M. leprae infects and interacts with host SCs is essential for understanding mechanisms of nerve damage and revealing potential new therapeutic strategies.Methodology/principal findingsWe performed a time-course single-cell sequencing analysis of SCs infected with M. leprae at different time points, further analyzed the heterogeneity of SCs, subpopulations associated with M. leprae infection, developmental trajectory of SCs and validated by Western blot or flow cytometry. Different subpopulations of SCs exhibiting distinct genetic features and functional enrichments were present. We observed two subpopulations associated with M. leprae infection, a stem cell-like cell subpopulation increased significantly at 24 h but declined by 72 h after M. leprae infection, and an adipocyte-like cell subpopulation, emerged at 72 h post-infection. The results were validated and confirmed that a stem cell-like cell subpopulation was in the early stage of differentiation and could differentiate into an adipocyte-like cell subpopulation.Conclusions/significanceOur results present a systematic time-course analysis of SC heterogeneity after infection by M. leprae at single-cell resolution, provide valuable information to understand the critical biological processes underlying reprogramming and lipid metabolism during M. leprae infection of SCs, and increase understanding of the disease-causing mechanisms at play in leprosy patients as well as revealing potential new therapeutic strategies.

BackgroundAssociations between trace elements and nasopharyngeal carcinoma (NPC) have been speculated but not thoroughly examined.MethodsThis study registered a total of 225 newly diagnosed patients with NPC and 225 healthy controls matched by sex and age from three municipal hospitals in Guangdong Province, southern China between 2011 and 2015. Information was collected by questionnaire on the demographic characteristics and other possibly confounding lifestyle factors. Eight trace elements and the level of Epstein–Barr virus (EBV) antibody were measured in casual (spot) serum specimens by inductively coupled plasma–mass spectrometry (ICP-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. Restricted cubic splines and conditional logistic regression were applied to assess the relationship between trace elements and NPC risk through single-and multiple-elements models.ResultsSerum levels of chromium (Cr), cobalt (Co), nickel (Ni), arsenic (As), strontium (Sr) and molybdenum (Mo) were not associated with NPC risk. Manganese (Mn) and cadmium (Cd) were positively associated with NPC risk in both single-and multiple-element models, with ORs of the highest tertile compared with the reference categories 3.90 (95% CI, 1.27 to 7.34) for Mn and 2.30 (95% CI, 1.26 to 3.38) for Cd. Restricted cubic splines showed that there was a linear increasing trend between Mn and NPC risk, while for Cd there was a J-type correlation.ConclusionSerum levels of Cd and Mn was positively related with NPC risk. Prospective researches on the associations of the two trace elements with NPC ought to be taken into account within the future.

Background: Idiopathic pulmonary arterial hypertension (PAH) is a potentially fatal pulmonary vascular disease with an extremely poor natural course. The limitations of current treatment and the unclear etiology and pathogenesis of idiopathic PAH require new targets and avenues of exploration involved in the pathogenesis of PAH. tRNA-derived small RNAs (tsRNAs), a new type of small non-coding RNAs, have a significant part in the progress of diverse diseases. However, the potential functions behind tsRNAs in idiopathic PAH remain unknown.Methods: Small RNA microarray was implemented on three pairs of plasma of idiopathic PAH patients and healthy controls to investigate and compare tsRNAs expression profiles. Validation samples were used for real-time polymerase chain reaction (Real-time PCR) to verify several dysregulated tsRNAs. Bioinformatic analysis was adopted to determine potential target genes and mechanisms of the validated tsRNAs in PAH.Results: Microarray detected 816 statistically significantly dysregulated tsRNAs, of which 243 tsRNAs were upregulated and 573 were downregulated in PAH. Eight validated tsRNAs in the results of Real-time PCR were concordant with the small RNA microarray: four upregulated (tRF3a-AspGTC-9, 5’tiRNA-31-GluCTC-16, i-tRF-31:54-Val-CAC-1 and tRF3b-TyrGTA-4) and four downregulated (5’tiRNA-33-LysTTT-4, i-tRF-8:32-Val-AAC-2, i-tRF-2:30-His-GTG-1, and i-tRF-15:31-Lys-CTT-1). The Gene Ontology analysis has shown that the verified tsRNAs are related to cellular macromolecule metabolic process, regulation of cellular process, and regulation of cellular metabolic process. It is disclosed that potential target genes of verified tsRNAs are widely involved in PAH pathways by Kyoto Encyclopedia of Genes and Genomes.Conclusion: This study investigated tsRNA profiles in idiopathic PAH and found that the dysregulated tsRNAs may become a novel type of biomarkers and possible targets for PAH.

From January 2020 to early 2022, for the first time, several Greater Spotted Eagles were recorded wintering in Xinjiang between the Tien Shan and Kunlun mountains.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. The development of biomarkers for early detection and monitoring of HCC has not shown significant progress. Meanwhile, the second adenomatous polyposis-related gene, MUTYH, which encodes a DNA glycosylase, has been observed in its contribution to oxidative DNA damage repair. Abnormal expression of MUTYH can reduce cell survival rate. Therefore, this study investigated the usefulness of MUTYH in diagnosing and prognosis HCC. Materials and methods: Using The Cancer Genome Atlas (TCGA) data, we analyzed the prognostic value of MUTYH in HCC. We used logistic regression, Wilcoxon signed-rank test, and Kruskal–Wallis test to examine MUTYH expression concerning clinical-pathologic characteristics. Univariate and multivariate Cox regression methods and Kaplan-Meier analysis were applied to determine the related prognostic factors of HCC. The enrichment analysis (GSEA) was used to determine the critical pathways associated with MUTYH. The single-sample gene set enrichment analysis (ssGSEA) was conducted to examine the correlation between MUTYH expression and cancer immune infiltration. Results: The higher expression of MUTYH in HCC patients was associated with a poorer overall survival rate and a shorter disease-specific survival rate. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that all differentially expressed genes (DEGs) between the high and low expression levels of MUTYH significantly enriched in the trace ligand-receptor interaction, cell cycle, oocyte meiosis, gap junction, and DNA replication. Group analysis revealed the signals of their open access. The neuron system, M phase, DNA repair, Rho GTPase effector, and cell cycle checkpoints were significantly enriched. ssGSEA showed a positive correlation between MUTYH expression and the infiltration levels of Th2 cells, NK cells, and T helper cells. Moreover, a negative correlation was found between MUTYH expression and the infiltration levels of dendritic cells (DCs) and cytotoxic cells. Conclusions: MUTYH expression levels were positively correlated with immune checkpoint gene expression levels in HCC tissues. The expression level of MUTYH was related to the prognosis of HCC and the immune infiltration of HCC.

K1/K2 hvKP strains acquire carbapenem-resistance plasmids, known as CR-hvKp, and carbapenem-resistant Klebsiella pneumoniae (CRKP) strains obtain virulence plasmids, recognized as hv-CRKP. The two different evolution patterns of hypervirulent combined carbapenem-resistant Klebsiella pneumoniae may lead to their different prevalence in hospitals. Our study aimed to investigate the prevalence of hv-CRKP and CR-hvKp strains and to analyze factors influencing their evolution and prevalence. We collected 890 K. pneumoniae genomes from GenBank and 530 clinical K. pneumoniae isolates from nine hospitals. Our study found that hv-CRKP strains were more prevalent than CR-hvKp strains and both were dominated by blaKPC-2 gene. The blaKPC-2-carrying plasmids could mobilize non-conjugative virulence plasmids from hvKp strains to CRKP strains. The conserved oriT of virulence plasmids and the widespread of conjugative helper plasmids were potential factors for the mobilization of non-conjugative virulence plasmids. HvKp strains with KPC plasmid could hardly simultaneously exhibit hypervirulence and carbapenem resistance as CRKP strains with virulence plasmid, and we found that rfaH mutation reduced capsular synthesis and increased carbapenem resistance of the CR-hvKp strain. In summary, this study revealed that hv-CRKP strains were more suitable for survival in hospital settings than CR-hvKp strains and the widespread conjugative KPC-producing plasmids contributed to the emergence and prevalence of hv-CRKP strains.

Immunosuppression as a result of severe infection impairs pathogen clearance and can increase susceptibility to secondary infection. Here, the authors dissect how T cell aging and the thymic involution that occurs during this process contribute to immunosuppression and find a key role for IL-33.

To ensure the reliability of the Wireless Power Transfer (WPT), the simultaneous wireless power and data transmission technology has gained more attention to realize real-time information exchange between the transmitter and receiver sides. In this paper, the shared channel technology and 2FSK modulation method are proposed to accomplish data and power transmission simultaneously. The theoretical analysis of the series-series compensation network is established, and the data modulation method through frequency-shifted modulation is analyzed. In order to reduce the bit error rate of transmitted data, a communication data format containing start and stop bits is proposed in this proposed system. Finally, an experimental prototype is constructed to validate the correctness and effectiveness of the proposed design and approach.

Air handling units (AHUs) are essential for the regulation and circulation of indoor air in modern buildings and for providing a comfortable environment. However, the performance of AHUs can be easily affected by various sensor faults during long-term operation. To precisely detect and diagnose AHU faults, many researchers have applied model-based and data-driven approaches based on existing centralized architectures. However, such methods require comprehensive knowledge of physical constraints or sufficient labeled data and thus are impractical in real scenarios. Inspired by the merits of emerging decentralized systems, we implement insect intelligent building (I2B), a fully decentralized architecture, for intelligent buildings to improve building operation performance. In addition, to ensure the AHU efficiency, we optimize the process of AHU fault detection and diagnosis and propose a fully distributed voting strategy using only adjacent computing process nodes (CPNs) in a decentralized architecture. Extensive experiments were conducted to analyze the performance of the proposed method in different real scenarios. Based on a comparison with related state-of-the-art methods, the experimental results highlight the superiority of our method, which provides high accuracy, plug-in capability and strong adaptability.

Abstract Background Crohn's disease (CD) is a chronic non-specific inflammatory bowel disease. Current CD therapeutics cannot fundamentally change the natural course of CD. Therefore, it is of great significance to find new treatment strategies for CD. Preclinical and clinical studies have shown that mesenchymal stromal cells (MSCs) are a promising therapeutic approach. However, the mechanism by which MSCs alleviate CD and how MSCs affect gut microbes are still unclear and need further elucidation. Methods We used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in mice and analysed the microbiota in faecal samples from the control group, the TNBS group and the TNBS + MSC group with faecal 16S rDNA sequencing. Subsequent analyses of alpha and beta diversity were all performed based on the rarified data. PICRUStII analysis was performed on the 16S rRNA gene sequences to infer the gut microbiome functions. Results MSC Treatment improved TNBS-induced colitis by increasing survival rates and relieving symptoms. A distinct bacterial signature was found in the TNBS group that differed from the TNBS + MSC group and controls. MSCs prevented gut microbiota dysbiosis, including increasing α-diversity and the amount of Bacteroidetes Firmicutes and Tenericutes at the phylum level and decreasing the amount of Proteobacteria at the phylum level. MSCs alleviated the increased activities of sulphur and riboflavin metabolism. Meanwhile some metabolic pathways such as biosynthesis of amino acids lysine biosynthesis sphingolipid metabolism and secondary bile acid biosynthesis were decreased in the TNBS group compared with the control group and the TNBS + MSC group Conclusions Overall, our findings preliminarily confirmed that colitis in mice is closely related to microbial and metabolic dysbiosis. MSC treatment could modulate the dysregulated metabolism pathways in mice with colitis, restoring the abnormal microbiota function to that of the normal control group. This study provides insight into specific intestinal microbiota and metabolism pathways linked with MSC treatment, suggesting a new approach to the treatment of CD.

Abstract Background To investigate the epidemiology of Klebsiella pneumoniae (K. pneumoniae) inducing pyogenic liver abscess (PLA) in east China and the role of hypervirulent carbapenem-resistant K. pneumoniae (Hv-CRKP). Methods Forty-three K. pneumoniae strains were collected from 43 patients with PLA at Hangzhou, China in 2017. Antimicrobial susceptibility tests, string test, multilocus sequence typing, pulsed-field gel electrophoresis, mobile genetic elements typing, regular PCR and sequencing, and Galleria mellonella (G. mellonella) lethality test were used to elucidate the epidemiology. Clinical data were collected. Results K. pneumoniae strains with serotypes K1 and K2 accounted for 69.8%, which shared 46.5% and 23.3% respectively. K. pneumoniae strains with clonal group 23 were predominant with a rate of 34.9%. Such antimicrobials showed susceptible rates over 80.0%: cefuroxime, cefotaxime, gentamycin, ticarcillin/clavulanate, ceftazidime, cefoperazone/tazobactam, cefepime, aztreonam, imipenem, meropenem, amikacin, tobramycin, ciprofloxacin, levofloxacin, doxycycline, minocycline, tigecycline, chloramphenicol, and trimethoprim-sulfamethoxazole. PFGE dendrogram showed 29 clusters for the 43 K. pneumoniae strains. Three Hv-CRKP strains were confirmed by G. mellonella lethality test, showing a constituent ratio of 7.0% (3/43). Totally three deaths were found, presenting a rate of 7.0% (3/43). The three died patients were all infected with Hv-CRKP. Conclusions K1 and K2 are the leading serotypes of K. pneumoniae causing PLA, which show highly divergent genetic backgrounds. Aminoglycosides, Generation 2nd to 4th cephalosporins, β-lactamase/β-lactamase inhibitors, carbapenems, fluoroquinolones are empirical choices. Hv-CRKP may confer an urgent challenge in the future.

Background: Osteosarcoma is one of the most prevalent bone malignancies with a poor prognosis. The N7-methylguanosine (m7G) modification facilitates the modification of RNA structure and function tightly associated with cancer. Nonetheless, there is a lack of joint exploration of the relationship between m7G methylation and immune status in osteosarcoma. Methods: With the support of TARGET and GEO databases, we performed consensus clustering to characterize molecular subtypes based on m7G regulators in all osteosarcoma patients. The least absolute shrinkage and selection operator (LASSO) method, Cox regression, and receiver operating characteristic (ROC) curves were employed to construct and validate m7G-related prognostic features and derived risk scores. In addition, GSVA, ssGSEA, CIBERSORT, ESTIMATE, and gene set enrichment analysis were conducted to characterize biological pathways and immune landscapes. We explored the relationship between risk scores and drug sensitivity, immune checkpoints, and human leukocyte antigens by correlation analysis. Finally, the roles of EIF4E3 in cell function were verified through external experiments. Results: Two molecular isoforms based on regulator genes were identified, which presented significant discrepancies in terms of survival and activated pathways. Moreover, the six m7G regulators most associated with prognosis in osteosarcoma patients were identified as independent predictors for the construction of prognostic signature. The model was well stabilized and outperformed traditional clinicopathological features to reliably predict 3-year (AUC = 0.787) and 5-year (AUC = 0.790) survival in osteosarcoma cohorts. Patients with increased risk scores had a poorer prognosis, higher tumor purity, lower checkpoint gene expression, and were in an immunosuppressive microenvironment. Furthermore, enhanced expression of EIF4E3 indicated a favorable prognosis and affected the biological behavior of osteosarcoma cells. Conclusions: We identified six prognostic relevant m7G modulators that may provide valuable indicators for the estimation of overall survival and the corresponding immune landscape in patients with osteosarcoma.

IntroductionHypervirulent Klebsiella pneumoniae produce an increased amount of capsular substance and are associated with a hypermucoviscous phenotype. Capsule production is regulated by capsular regulatory genes and capsular gene cluster variations. In the present study, we focus on the effect of rmpA and wcaJon capsule biosynthesis.MethodsPhylogenetic trees were constructed to analyze wcaJ and rmpA sequence diversity in different serotypes hypervirulent strains. Then mutant strains (K2044ΔwcaJ, K2044K1wcaJ, K2044K2wcaJand K2044K64wcaJ) were used to verify the effects of wcaJ and its diversity on capsule synthesis and strain virulence. Furthmore, the role of rmpA in capsular synthesis and its mechanisms were detected in K2044ΔrmpA strain.ResultsRmpA sequences are conversed in different serotypes. And rmpA promoted the production of hypercapsules by simultaneously acting on three promoters in cps cluster. Whereas wcaJ, its sequences are different in different serotypes, and its loss result in the termination of capsular synthesis. Moreover, the results verified that K2 wcaJ could form hypercapsule in K2044 strains (K1 serotype), but K64 wcaJ could not.DiscussionThe interaction of multiple factors is involved in capsule synthesis, including wcaJ and rmpA. RmpA, an known conserved capsular regulator gene, acts on cps cluster promoters to promote the production of the hypercapsule. WcaJ as initiating enzyme of CPS biosynthesis, its presence determines the synthesis of capsule. Besides, different from rmpA, wcaJ sequence consistency is limited to the same serotype, which cause wcaJ functioning in different serotype strains with sequence recognition specificity.

Gefitinib (GEF) is a clinical medication for the treatment of lung cancer targeting the epidermal growth factor receptor (EGFR). However, its efficacy is remarkably limited by low solubility and dissolution rates. In this study, two cocrystals of GEF with co-formers were successfully synthesized using the recrystallization method characterized via Powder X-ray Diffraction, Fourier Transform Infrared Spectroscopy, and 2D Nuclear Overhauser Effect Spectroscopy. The solubility and dissolution rates of cocrystals were found to be two times higher than those of free GEF. In vitro cytotoxicity studies revealed that the cocrystals enhanced the inhibition of cell proliferation and apoptosis in A549 and H1299 cells compared to free GEF. In mouse models, GEF@TSBO demonstrated targeted, safe, and effective antitumor activity with only one-dose administration. Mechanistically, the GEF cocrystals were shown to increase the cellular levels of damaged DNA, while potentially downregulating PARP, thereby impairing the DNA repair machinery and leading to an imbalance between DNA damage and restoration. These findings suggest that the cocrystallization of GEF could serve as a promising adjunct to significantly enhance the physicochemical and biopharmaceutical performance for lung cancer treatment, providing a facial strategy to improve GEF anticancer efficiency with high bioavailability that can be orally administrated with only one dose.

Abstract Power flow controller (PFC), fault current limiter (FCL) and DC circuit breaker (DCCB) are important equipment in the DC grid. There are a large number of power electronic components in these equipment, resulting in high cost. In order to reduce the use of additional components, a current‐limiting DC circuit breaker with power flow control capability is proposed here, which integrates the PFC, FCL, and DCCB into one equipment. Further, the main breaker in the proposed circuit breaker is shared by all lines connected to a DC bus to reduce cost. The topology and operating principle of the circuit breaker are introduced. Theoretical analysis and parameter design are carried out. Besides, the proposed circuit breaker is verified in PSCAD/EMTDC. Finally, the performance and cost are compared with existing schemes. The simulation results show that the proposed circuit breaker can effectively realize power flow control, current limiting and fault isolation at a lower cost.

PurposeTo investigate the mechanisms of Klebsiella pneumoniae-induced pyogenic liver abscess (PLA).MethodsForty-three K. pneumoniae strains from PLAs and 436 from non-PLAs were collected. Their differences were compared for virulence genes and factors, sequence types, and serotypes. Virulence genes wzi, wzy-K1, and wzi+wzy-K1 were deleted in K. pneumoniae NTUH-K2044. Various analyses, such as transmission electron microscopy, neutrophil killing tests, and mouse lethality tests, were used to confirm the consequent changes.ResultsDifferences were found between K. pneumoniae strains from PLA and non-PLA samples for virulence genes and factors, including metabolism genes (allS and peg-344), capsular polysaccharide (CPS)-synthesis channel gene (wzy-K1), CPS-regulating genes (p-rmpA, p-rmpA2, and c-rmpA), and siderophore genes (iucA and iroN). When wzy-K1 was positive, the difference between PLA and non-PLA samples was only observed with c-rmpA. Δwzi, Δwzy-K1, and ΔwziΔwzy-K1 strains reverted to hypovirulence. In the Kupffer cell stimulation assay, interleukin (IL)-6, IL-12, IL-10, and transforming growth factor-β secretions were found to be equivalent in NTUH-K2044, Δwzi, Δwzy-K1, and ΔwziΔwzy-K1 groups. Lower IL-1β and higher tumor necrosis factor-α secretions were observed for Δwzi, Δwzy-K1, and ΔwziΔwzy-K1.ConclusionsHypercapsule production is the cornerstone of hypervirulence, regardless of exopolysaccharides. K1 K. pneumoniae-induced PLA may decrease core inflammatory cytokines rather than increase anti-inflammatory cytokines. Exopolysaccharides could also attenuate the inflammatory response to aid in the immune escape of K. pneumoniae.