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Serving as the guardians of small intestine, Paneth cells (PCs) play an important role in intestinal homeostasis maintenance. Although PCs uniquely exist in intestine under homeostasis, the dysfunction of PCs is involved in various diseases not only in intestine but also in extraintestinal organs, suggesting the systemic importance of PCs. The mechanisms under the participation of PCs in these diseases are multiple as well. The involvements of PCs are mostly characterized by limiting intestinal bacterial translocation in necrotizing enterocolitis, liver disease, acute pancreatitis and graft-vs-host disease. Risk genes in PCs render intestine susceptible to Crohn’s disease. In intestinal infection, different pathogens induce varied responses in PCs, and toll-like receptor ligands on bacterial surface trigger the degranulation of PCs. The increased level of bile acid dramatically impairs PCs in obesity. PCs can inhibit virus entry and promote intestinal regeneration to alleviate COVID-19. On the contrary, abundant IL-17A in PCs aggravates multi-organ injury in ischemia/reperfusion. The pro-angiogenic effect of PCs aggravates the severity of portal hypertension. Therapeutic strategies targeting PCs mainly include PC protection, PC-derived inflammatory cytokine elimination, and substituting AMP treatment. In this review, we discuss the influence and importance of Paneth cells in both intestinal and extraintestinal diseases as reported so far, as well as the potential therapeutic strategies targeting PCs.

Federated learning (FL) has gained popularity in clinical research in recent years to facilitate privacy-preserving collaboration. Structured data, one of the most prevalent forms of clinical data, has experienced significant growth in volume concurrently, notably with the widespread adoption of electronic health records in clinical practice. This review examines FL applications on structured medical data, identifies contemporary limitations and discusses potential innovations. We searched five databases, SCOPUS, MEDLINE, Web of Science, Embase, and CINAHL, to identify articles that applied FL to structured medical data and reported results following the PRISMA guidelines. Each selected publication was evaluated from three primary perspectives, including data quality, modeling strategies, and FL frameworks. Out of the 1160 papers screened, 34 met the inclusion criteria, with each article consisting of one or more studies that used FL to handle structured clinical/medical data. Of these, 24 utilized data acquired from electronic health records, with clinical predictions and association studies being the most common clinical research tasks that FL was applied to. Only one article exclusively explored the vertical FL setting, while the remaining 33 explored the horizontal FL setting, with only 14 discussing comparisons between single-site (local) and FL (global) analysis. The existing FL applications on structured medical data lack sufficient evaluations of clinically meaningful benefits, particularly when compared to single-site analyses. Therefore, it is crucial for future FL applications to prioritize clinical motivations and develop designs and methodologies that can effectively support and aid clinical practice and research.

Additional file 8. Review history.

Additional file 1: Fig. S1. Relative concentrations of identified bile acids in AL and CR groups. Fig.S2. The phenotypes of HFD male mice after CR gut microbiota transplantation. Fig. S3. Cecal gut microbiota composition alterations in donor groups and recipient groups. Fig. S4. Relative concentrations of identified bile acids in HFD and HFDR groups. Table S1. The caloric consumption in the study. Table S2. The components of the diet sused in the study. Table S3. Primary antibodies used in this study. Table S4. Sequences of primers for RT-qPCR. Table S5. Sequences of primers for ChIP-qPCR.

The two-phase sampling design is a cost-effective sampling strategy that has been widely used in public health research. The conventional approach in this design is to create subsample specific weights that adjust for probability of selection and response in the second phase. However, these weights can be highly variable which in turn results in unstable weighted analyses. Alternatively, we can use the rich data collected in the first phase of the study to improve the survey inference of the second phase sample. In this paper, we use a Bayesian tree-based multiple imputation (MI) approach for estimating population means using a two-phase survey design. We demonstrate how to incorporate complex survey design features, such as strata, clusters, and weights, into the imputation procedure. We use a simulation study to evaluate the performance of the tree-based MI approach in comparison to the alternative weighted analyses using the subsample weights. We find the tree-based MI method outperforms weighting methods with smaller bias, reduced root mean squared error, and narrower 95\% confidence intervals that have closer to the nominal level coverage rate. We illustrate the application of the proposed method by estimating the prevalence of diabetes among the United States non-institutionalized adult population using the fasting blood glucose data collected only on a subsample of participants in the 2017-2018 National Health and Nutrition Examination Survey.

Dynamic treatment regimes (DTRs) are sequences of decision rules that recommend treatments based on patients' time-varying clinical conditions. The sequential multiple assignment randomized trial (SMART) is an experimental design that can provide high-quality evidence for constructing optimal DTRs. In a SMART, participants are randomized to available treatments at multiple stages, typically following a fixed and balanced randomization procedure. Despite its relative simplicity of implementation and desirable performance in comparing embedded DTRs, the SMART with balanced randomization (SMART-BR) is faced with inevitable ethical issues including assigning many participants to the observed inferior treatment or the treatment they dislike, which might slow down the recruitment procedure and lead to higher attrition rates. In this context, we propose a SMART under the Experiment-as-Market framework (SMART-EXAM), a novel SMART design that holds the potential to improve patient welfare by incorporating participants' preferences and predicted treatment effects into the randomization procedure. We describe the procedure of conducting a SMART-EXAM and evaluate its theoretical and empirical statistical properties compared with other competing SMART designs. The results indicate that the SMART-EXAM design can improve the welfare of participants enrolled in the trial, while also achieving a comparable ability to construct an optimal DTR. We finally illustrate the practical potential of the SMART-EXAM design using data from a SMART for children with attention-deficit/hyperactivity disorder (ADHD).

Marine methane hydrate is an important source of energy for the future, attracting great attention of global researchers and many governments. The water-saturated hydrate deposit is more similar to...

Additional file 1: Figure S1. Sperm kinematic parameters measured by computer assisted semen analysis (CASA). ALH, amplitude of lateral head displacement; BCF, beat cross frequency; LIN, linearity; MAD, mean angular displacement; STR, straightness; VAP, average path velocity; VCL, curvilinear velocity; VSL, straight line velocity; WOB, curvilinear path wobble. Figure S2. Flowchart of participants in the study. Normal semen quality group defined by semen volume ��� 1.5 ml, sperm concentration ��� 15 �� 106/ml, total sperm number ��� 39 �� 10,6 and total motility ���40%. Abnormal semen quality group defined by at least one abnormal semen parameters (semen volume, sperm concentration, total sperm number or sperm motility). Figure S3. Distribution of daily temperatures in Nanjing between 2014 and 2016. The points in top and bottom graphs indicate daily temperatures. Figure S4. Distribution of daily PM10 in Nanjing between 2014 and 2016. The points in top and bottom graphs indicate daily PM10. The straight black line indicates Chinese 24-h standard (Grade II) for PM10 (150 ��g/m3). Table S1. Coefficient of correlation between the semen parameters. Table S2. Distribution of air pollutant exposure for study subjects. Table S3. Coefficients from linear regression for PM10 exposure in relation to semen parameters by exposure period (0-90, 0-9, 10-14, 15-69, 70-90 days) prior to semen collection in all participants (n = 1554) expressed as change in the parameter for a 10 ��g/m3 increase in exposure. Table S4. Coefficients from linear regression for PM2.5 exposure in relation to semen parameters by exposure period (0-90, 0-9, 10-14, 15-69, 70-90 days) prior to semen collection in normal and abnormal semen parameters groups expressed as change in the parameter for a 10 ��g/m3 increase in exposure. Table S5. Coefficients from linear regression for PM10 exposure in relation to semen parameters by exposure period (0-90, 0-9, 10-14, 15-69, 70-90 days) prior to semen collection in normal and abnormal semen parameters groups expressed as change in the parameter for a 10 ��g/m3 increase in exposure. Table S6. Coefficients (95% CIs) from linear regression of PM2.5 exposure during 0-90 days before semen collection in relation to sperm parameters in normal semen parameters group expressed as change in the parameter for a 10 ��g/m3 increase in exposure. Table S7. Coefficients (95% CIs) from linear regression of PM2.5 exposure during 0-90 days before semen collection in relation to sperm parameters in abnormal semen parameters group expressed as change in the parameter for a 10 ��g/m3 increase in exposure. Table S8. Coefficients from linear regression for PM2.5 exposure in relation to total sperm motility by categories of age, BMI, income, cigarette smoking and alcohol drinking expressed as change in the parameter for a 10 ��g/m3 increase in exposure. Table S9. Characteristics and main results of previous studies examined the association between PM and semen quality.

Additional file 1: Supplemental Table 1. Details and sources of the 46 Monochasma savatieri samples analyzed in this study. Supplemental Fig. 1. The representative gel pictures with scoring by the EST-SSR markers. The patterns of bands were analyzed by a gel imaging analysis system (version Tocan 240). Supplemental Fig. 2. The photos of some representative samples in this study.

Mobile technology enables unprecedented continuous monitoring of an individual's behavior, social interactions, symptoms, and other health conditions, presenting an enormous opportunity for therapeutic advancements and scientific discoveries regarding the etiology of psychiatric illness. Continuous collection of mobile data results in the generation of a new type of data: entangled multivariate time series of outcome, exposure, and covariates. Missing data is a pervasive problem in biomedical and social science research, and the Ecological Momentary Assessment (EMA) using mobile devices in psychiatric research is no exception. However, the complex structure of multivariate time series introduces new challenges in handling missing data for proper causal inference. Data imputation is commonly recommended to enhance data utility and estimation efficiency. The majority of available imputation methods are either designed for longitudinal data with limited follow-up times or for stationary time series, which are incompatible with potentially non-stationary time series. In the field of psychiatry, non-stationary data are frequently encountered as symptoms and treatment regimens may experience dramatic changes over time. To address missing data in possibly non-stationary multivariate time series, we propose a novel multiple imputation strategy based on the state space model (SSMmp) and a more computationally efficient variant (SSMimpute). We demonstrate their advantages over other widely used missing data strategies by evaluating their theoretical properties and empirical performance in simulations of both stationary and non-stationary time series, subject to various missing mechanisms. We apply the SSMimpute to investigate the association between social network size and negative mood using a multi-year observational smartphone study of bipolar patients, controlling for confounding variables.

The characteristics of inhalable particulate matter (PM2.5, PM10) in urban subway stations can have a major impact on passengers’ health. Existing research largely fails to focus on different environmental control systems and there are few studies focused on different pollution conditions. This study therefore focused on measuring and comparing the characteristics of PM2.5 and PM10 at subway stations with three control systems in Beijing different pollution conditions. Stations including three types of control system (open, closed and screen door) and outside were monitored and analyzed using a general linear model. The concentration of PM2.5 and PM10 at different locations, such as on platforms, in carriages and in working areas, was compared and analyzed under different external pollution conditions. The results show that at different environment control systems the characteristics of PM2.5 and PM10 are different. The concentrations of particles in closed system are generally higher than screen system at platform. While the pollution in carriage is heavier for open system than that of screen system. The PM2.5/PM10 ratio was 91%, 90% and 83.84% at closed, open and screen system, respectively. While, the PM2.5 and PM10 levels inside the stations were strongly correlated with the outdoor conditions regardless of the environmental control system. This is the first study to show the PM concentration characteristics for different subway environmental control systems. As such, it provides a solid foundation for air clean studies at subway stations with different control systems.

We study the effect of the strain on the band structure and the valley-dependent transport property of graphene heterojunctions. It is found that valley-dependent separation of electrons can be achieved by utilizing the strain and on-site energies. In the presence of the strain, the values of the transmission can be effectively adjusted by changing the strengths of the strain, while the transport angle basically keeps unchanged. When an extra on-site energy is simultaneously applied to the central scattering region, not only are the electrons of valleys K and K' separated into two distinct transmission lobes in opposite transverse directions, but the transport angles of two valleys can be significantly changed. Therefore, one can realize an effective modulation of valley-dependent transport by changing the strength and stretch angle of the strain and on-site energies, which can be exploited for graphene-based valleytronics devices., 7 pages, 10 figures

Background: Peroxisome proliferator-activated receptor alpha (PPARα) is associated with diabetic retinopathy (DR), and the underlying mechanism is still unclear. Aim of this work was to investigate the mechanism of PPARα in DR. Methods: Human retinal capillary pericytes (HRCPs) were treated with high glucose (HG) to induce DR cell model. DR mouse model was established by streptozotocin injection, and then received 5-Aza-2-deoxycytidine (DAC; DNA methyltransferase inhibitor) treatment. Hematoxylin–eosin staining was performed to assess retinal tissue damage. PPARα methylation was examined by Methylation-Specific PCR. Flow cytometry and DCFH-DA fluorescent probe was used to estimate apoptosis and reactive oxygen species (ROS). The interaction between DNA methyltransferase-1 (DNMT1) and PPARα promoter was examined by Chromatin Immunoprecipitation. Quantitative real-time PCR and western blot were performed to assess gene and protein expression. Results: HG treatment enhanced the methylation levels of PPARα, and repressed PPARα expression in HRCPs. The levels of apoptotic cells and ROS were significantly increased in HRCPs in the presence of HG. Moreover, DNMT1 was highly expressed in HG-treated HRCPs, and DNMT1 interacted with PPARα promoter. PPARα overexpression suppressed apoptosis and ROS levels of HRCPs, which was rescued by DNMT1 up-regulation. In DR mice, DAC treatment inhibited PPARα methylation and reduced damage of retinal tissues. Conclusion: DNMT1-mediated PPARα methylation promotes apoptosis and ROS levels of HRCPs and aggravates damage of retinal tissues in DR mice. Thus, this study may highlight novel insights into DR pathogenesis.

BACKGROUND: Challenges in medical care posed by rapid tumor progression, individualized responses to therapy, and the heterogeneous characteristics of breast cancer (BRCA) highlight the urgent need for new treatment strategies, as well as therapeutic and prognostic markers. Accumulating evidence has revealed that microRNAs broadly participate in carcinogenesis, but our understanding of the role of miR-93-5p in BRCA remains limited. METHODS: The prognosis of miR-93-5p, programmed cell death-ligand 1 (PD-L1) and CCND1 were analyzed by datasets. Freshly excised breast cancer tissues (N=33) and adjacent noncancerous tissues (N=18) were collected to detect the expression of CCND1 and PD-L1 by immunohistochemistry (IHC). Quantitative real-time PCR (qRT-PCR) and Western blot were used to test the expression of miR-93-5p, PD-L1 and CCND1 after transfected mimics or inhibitors. Dual-luciferase reporter assay indicates the direct targeting between miR-93-5p and PD-L1. RESULTS: Bioinformatics analysis demonstrated that miR-93-5p plays differential roles in various tumors, and further verification using qRT-PCR revealed that the expression levels of miR-93-5p were lower in MDA-MB-231 cells than in noncancerous breast cells. In addition, we confirmed that PD-L1 and CCND1 generated mutual effects, and miR-93-5p directly targets the PD-L1/CCND1 signaling pathway to influence their accumulation and distribution in the cell membrane, nucleus, and cytoplasm, mediating tumor progression and immune regulation in BRCA. CONCLUSIONS: Taken together, miR-93-5p could regulate tumorigenesis and tumor immunity by targeting PD-L1/CCND1 in BRCA and our research provides a rationale for therapy with miR-93-5p to overcome immune escape and improve risk stratification.

Hydrate reservoirs with underlying gas are generally accepted as the most promising energy resource for commercial exploitation. The underlying gas is an important part of the energy recovery of hydrate reservoirs. However, the gas production characteristics of hydrate reservoirs with underlying gas are rarely discussed. This paper aims to analyze the effects of underlying gas on the formation of hydrate and methane production behaviors by depressurization. In a core holder, marine soil obtained from the South China Sea was used to remold muddy low-permeability cores. The hydrate saturation of the muddy cores ranged from 25.2% to 48.3%. In this work, when the pressure difference between the underlying gas and the hydrate phase equilibrium is less than 2.6 MPa, the underlying gas pressure is the decisive factor for hydrate saturation. Besides, underlying gas can provide a relatively slow pressure drop rate for hydrate decomposition. The low permeability of the core caused by high hydrate saturation weakens the production of underlying gas and leads to the pressure gradient in the core. Hydrate decomposition front advances with the pressure gradient. Therefore, the production of underlying gas and hydrate decomposition are interdependent during depressurization. The experimental results demonstrated the existence of underlying gas could boost the exploitation potential and gas recoverability of hydrate reservoirs. These findings expand the understanding of joint exploitation characteristics and provide guidance in assessing the production potential for further researches and field exploitation of hydrate reservoirs with underlying gas.

In order to enhance the visible-light transmittance while reducing the insulator–metal transition (IMT) temperature, Hf–W co-doping is designed for modification of VO2. We grow high-quality HfxWyV1−x−yO2 (HfWVO2) alloy films on c-plane sapphire substrates by pulsed laser deposition, and test structural, electrical, and optical properties of the films by various techniques. The Hf–W co-doped VO2 films exhibit outstanding thermochromic performances with a high luminous transmittance up to 41.1%, a fairly good near-infrared modulation capacity of 13.1%, and a low phase transition temperature of 38.9 °C. The enhanced luminous transmittance along with reduced IMT temperature in HfWVO2 is attributed to the co-doping synergetic effect of Hf and W, which effectively improves the optical bandgap and donates extra electrons into the system, respectively, while largely retaining the near-infrared modulation capacity of VO2. Our work provides an effective strategy in tailoring VO2 toward practical smart-coating applications by Hf–W co-doping.

Overshoot and undershoot resulted from line/load/reference change can degrade the power efficiency of a voltage regulator. A pulse width modulation (PWM) skipping technique is thus proposed to reduce such voltage fluctuation. A four-phase interleaved buck converter is experimented to verify the merits of the proposed technique. In steady-state operation, all four phases of the buck converter are driven by a PWM controller to regulate the output voltage. During transient response, the PWM-skipping technique bypasses the PWM controller to drive some phases of the buck converter into charging or discharging state. Simulation results demonstrate that the proposed PWM-skipping technique effectively reduces overshoot and undershoot by more than 25% when the buck converter responds to line/load/reference change.

In order to improve the response speed and stability of the BP neural network controlled permanent magnet synchronous motor speed control process, an improved genetic algorithm is proposed to optimize the BP neural network. The algorithm optimizes the initial distribution of chromosomes on the one hand, and dynamically adjusts on the other hand. The cross-mutation probability formula improves the global search ability of the genetic algorithm, and optimizes the BP neural network weight update strategy. The model is built and simulated in the MATLAB/Simulink environment. The simulation results show that the improved genetic algorithm is used. The response speed of the permanent magnet synchronous motor speed control system with optimized parameters is improved, the anti-interference ability and tracking performance are improved, and the convergence speed of the BP neural network is improved.

This paper studies the mechanism of ultra-large-scale drug virtual screening in the heterogeneous multicore environment and SMP (Symmetric Multi-Processor) environment. Given the differences caused by different CPUs, we solved the incompatibility of the open-source molecular docking software Autodock Vina on two supercomputer systems in different environments and realized the automatic and intelligent large-scale virtual screening process for small-molecule ligands. At the same time, we propose a processing method of large-scale virtual screening using Autodock Vina in two environments, which makes full use of the dominant computing power of supercomputers to improve the efficiency of large-scale molecular docking and reduce the load of different supercomputer systems facing large-scale molecular docking tasks. Finally, we conduct a virtual screening experiment on the X86 platform supercomputer and the Sunway TaihuLight Supercomputer based on the heterogeneous multicore architecture CPU—SW26010. The experimental results show that our large-scale drug virtual screening method for different CPU environments is effective.

Spermatogenesis and sperm maturation are androgen-dependent processes. Steroid 5α-reductase (SRD5A) is a key enzyme converting testosterone into the more active metabolite, dihydrotestosterone (DHT). We aimed to investigate the association between the genetic variants of SRD5A2 (rs4952197, rs2268797, rs13395648, rs523349 and rs632148) and semen quality. Variant genotyping and semen analysis was performed in 708 males with definite idiopathic infertility by TaqMan SNP genotyping assays and computer-assisted semen analysis, respectively. It was found that the rs13395648 TC genotype was associated with a significantly lower semen volume compared with the TT genotype (P=0.016). The same trend was found between the combination of the TC and CC genotypes and the TT genotype (P=0.020). With regard to variant rs632148, subjects with the GC genotype had significantly lower sperm motility in comparison to those with the GG genotype (P=0.029). The sperm motility between the combination of the GC and CC genotypes and the GC genotype was also significantly different (P=0.033). These findings indicate that genetic variants in the SRD5A2 gene may be associated with semen quality.

Photovoltaic/thermal (PV/T) systems play an important role in solar system development, reducing pollution, and meeting the rapid increase in energy demand. PV/T can significantly improve energy transfer efficiency, hence improving its performance attracted extensive research attention. Different structures of the solar collector are proposed. To reduce the investment and cost of the experiment, several prediction studies are also conducted, as modeling its performance is meaningful for the optimization and design of the system.\ud In this thesis, we study a photovoltaic/thermal assisted air source heat pump (PV/T-ASHP) system with a novel absorber of the solar collector in Beijing. It is shown that for the whole year the electricity self-sufficiency is over 50 % and the heat self-sufficiency is 30.7 % in extreme conditions for the heating systems (e.g., December). Ambient temperature and solar irradiation change highly affect the performance of the whole system. In extreme weather e.g., a sunny day in December, the average COP is higher than 3.5. The payback time for this system is 9.5 years, and it reduces equivalent to 6.8 t of carbon dioxide (CO2) emission per year. Based on the experiment results, we then predict the performance using an ANN. It is seen that the more considered factor, the higher the performance of the prediction model. It is also seen that in this case, an ANN with two hidden layers performs better than that of one hidden layer. Furthermore, the comparison results suggest that in practice it is required to find the best suitable ANN network before application.

The recruitment of substrates by the ser/thr protein phosphatase 2A (PP2A) is poorly understood, limiting our understanding of PP2A-regulated signaling. Recently, the first PP2A:B56 consensus binding motif, LxxIxE, was identified. However, most validated LxxIxE motifs bind PP2A:B56 with micromolar affinities, suggesting that additional motifs exist to enhance PP2A:B56 binding. Here, we report the requirement of a positively charged motif in a subset of PP2A:B56 interactors, including KIF4A, to facilitate B56 binding via dynamic, electrostatic interactions. Using molecular and cellular experiments, we show that a conserved, negatively charged groove on B56 mediates dynamic binding. We also discovered that this positively charged motif, in addition to facilitating KIF4A dephosphorylation, is essential for condensin I binding, a function distinct and exclusive from PP2A-B56 binding. Together, these results reveal how dynamic, charge-charge interactions fine-tune the interactions mediated by specific motifs, providing a new framework for understanding how PP2A regulation drives cellular signaling.

The recruitment of substrates by the ser/thr protein phosphatase 2A (PP2A) is poorly understood, limiting our understanding of PP2A-regulated signaling. Recently, the first PP2A:B56 consensus binding motif, LxxIxE, was identified. However, most validated LxxIxE motifs bind PP2A:B56 with micromolar affinities, suggesting that additional motifs exist to enhance PP2A:B56 binding. Here, we report the requirement of a positively charged motif in a subset of PP2A:B56 interactors, including KIF4A, to facilitate B56 binding via dynamic, electrostatic interactions. Using molecular and cellular experiments, we show that a conserved, negatively charged groove on B56 mediates dynamic binding. We also discovered that this positively charged motif, in addition to facilitating KIF4A dephosphorylation, is essential for condensin I binding, a function distinct and exclusive from PP2A-B56 binding. Together, these results reveal how dynamic, charge-charge interactions fine-tune the interactions mediated by specific motifs, providing a new framework for understanding how PP2A regulation drives cellular signaling.