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Abstract Background Regulatory T cells (Tregs) are crucial in maintaining immune homeostasis and preventing autoimmunity and inflammation. A proportion of Treg cells can lose Foxp3 expression and become unstable under inflammation conditions. The precise mechanisms underlying this phenomenon remain unclear. Methods The PI16 gene knockout mice (PI16fl/flFoxp3Cre) in Treg were constructed, and the genotypes were identified. The proportion and phenotypic differences of immune cells in 8-week-old mice were detected by cell counter and flow cytometry. Two groups of mouse Naïve CD4+T cells were induced to differentiate into iTreg cells to observe the effect of PI16 on the differentiation and proliferation of iTreg cells, CD4+CD25+Treg and CD4+CD25− effector T cells (Teff) were selected and co-cultured with antigen presenting cells (APC) to observe the effect of PI16 on the inhibitory ability of Treg cells in vitro. The effects of directed knockout of PI16 in Treg cells on inflammatory symptoms, histopathological changes and immune cell expression in mice with enteritis and autoimmune arthritis were observed by constructing the model of antigen-induced arthritis (AIA) and colitis induced by dextran sulfate sodium salt (DSS). Results We identified peptidase inhibitor 16 (PI16) as a negative regulator of Treg cells. Our findings demonstrate that conditional knock-out of PI16 in Tregs significantly enhances their differentiation and suppressive functions. The conditional knockout of the PI16 gene resulted in a significantly higher abundance of Foxp3 expression (35.12 ± 5.71% vs. 20.00 ± 1.61%, p = 0.034) in iTreg cells induced in vitro compared to wild-type mice. Mice with Treg cell-specific PI16 ablation are protected from autoimmune arthritis (AIA) and dextran sulfate sodium (DSS)-induced colitis development. The AIA model of PI16CKO is characterized by the reduction of joint structure and the attenuation of synovial inflammation and in DSS-induced colitis model, conditional knockout of the PI16 reduce intestinal structural damage. Additionally, we found that the deletion of the PI16 gene in Treg can increase the proportion of Treg (1.46 ± 0.14% vs. 0.64 ± 0.07%, p

In this paper, we introduce a new family of algebras $ {\mathcal{H}}_n $, which are generated by three generators $ x, y, z $, with the following relations: (1) $ x^{2n} = 1, \ y^2 = xy+y, \ xy = yx; $ and (2) $ z^2 = z, \ xz = zx = z, \ zy = 2z. $ First, it shows that $ {\mathcal{H}}_n $ is a positively based algebra. Then, all the indecomposable modules of $ {\mathcal{H}}_n $ are constructed. Additionally, it shows that the dimension of each indecomposable $ {\mathcal{H}}_n $-module is at most $ 2 $. Finally, all the left (right) cells and left (right) cell modules of $ {\mathcal{H}}_n $ are described, and the decompositions of the decomposable left cell modules are also obtained.

Early diagnosis of Bell's palsy is crucial for effective patient management in primary care settings. This study aimed to develop a simplified diagnostic tool to enhance the accuracy of identifying Bell's palsy among patients with facial muscle weakness. Data from 240 patients were analyzed using seven potential clinical evaluation indicators. Two diagnostic benchmarks were established: one based on clinical assessment and the other incorporating magnetic resonance imaging (MRI) findings. A multivariate logistic regression model was developed based on these benchmarks, resulting in the construction of a predictive tool evaluated through latent class models. Both models retained four key clinical indicators: absence of forehead wrinkles, accumulation of food and saliva inside the mouth on the affected side, presence of vesicular rash in the ear or pharynx, and lack of pain or symptoms associated with tick exposure, rash, or joint pain. The first model demonstrated excellent discriminative ability (area under the curve [AUC] = 0.96, 95% confidence interval [CI] 0.94 - 0.99) and calibration (P < 0.001), while the second model also showed good performance (AUC = 0.88, 95% CI 0.83 - 0.92) and calibration (P = 0.005). Bootstrap validation indicated no significant overfitting. The latent class defined by the first model significantly aligned with the clinical diagnosis group, while the second model showed lower consistency.

Abstract Batteries dissolving active materials in liquids possess safety and size advantages compared to solid‐based batteries, yet the intrinsic liquid properties lead to material cross‐over induced self‐discharge both during cycling and idle when the electrolytes are in contact, thus highly efficient and cost‐effective solutions to minimize cross‐over are in high demand. An ultra‐low self‐discharge aqueous|organic membraneless battery using dichloromethane (CH2Cl2) and tetrabutylammonium bromide (TBABr) added to a zinc bromide (ZnBr2) solution as the electrolyte is demonstrated. The polybromide is confined in the organic phase, and bromine (Br2) diffusion‐induced self‐discharge is minimized. At 90% state of charge (SOC), the membraneless ZnBr2|TBABr (Z|T) battery shows an open circuit voltage (OCV) drop of only 42 mV after 120 days, 152 times longer than the ZnBr2 battery, and superior to 102 previous reports from all types of liquid active material batteries. The 120‐day capacity retention of 95.5% is higher than commercial zinc‐nickel (Zn–Ni) batteries and vanadium redox flow batteries (VRFB, electrolytes stored separately) and close to lithium‐ion (Li‐ion) batteries. Z|T achieves >500 cycles (2670 h, 0.5 m electrolyte, 250 folds of membraneless ZnBr2 battery) with ≈100% Coulombic efficiency (CE). The simple and cost‐effective design of Z|T provides a conceptual inspiration to regulate material cross‐over in liquid‐based batteries to realize extended operation.

In an era marked by escalating demand for water resources and expanding human encroachment, numerous regions worldwide find it very challenging to balance water supply and demand. As a key source of water yield services, ecosystems often fail to spatially satisfy the great demand for water resources in some areas. This study focuses on the role of ecosystems in the supply and demand of water yield services in human social systems and then maps the flow between them. It quantifies their intricate relationship by employing the concept of ecosystem service flow. A notable gap exists in methodologies that intuitively illustrates the 'supply-movement-demand' dynamics in this context. Consequently, this study introduces a comprehensive methodology by integrating multiple models such as 'InVEST-Geoda-Gephi' to investigate the transmission paths and characteristics of surplus and deficit distribution of water yield service flow across various scales. Firstly, the spatiotemporal evolution of water yield service supply and demand within ecosystems is analyzed. Secondly, we scrutinize regional supply and demand alignment spatial patterns utilizing the Geoda model. Subsequently, the Gephi network model simulates water yield service flow from ecosystems to human social systems. The findings corroborate the network model's effectiveness and visual capabilities in representing ecosystem service flow across diverse scales. The primary conclusions drawn are as follows: (a) The spatiotemporal distribution of water yield services around the Wuyi Mountains exhibited a pattern characterized as 'high in the center, low on the edges' from 2000 to 2020, revealing significant spatial heterogeneity between high-supply and high-demand areas; (b) Influenced by the mountainous region's supply, the study area was mainly characterized by a high-low spatial mismatch. High-high spatial match was mainly distributed in provincial capitals and selected coastal economic zones. In contrast, low-low spatial match transitioned from northwest to southwest, and low–high mismatch encircled in areas featuring both high supply and high demand, particularly around provincial capitals and adjacent undeveloped coastal regions; (c) With the advance of urbanization and economic development, deficit nodes in the water yield service flow network tended to be marginalized, which reduced network density and connectivity leading to a decline in the ability of Wuyi Mountains ecosystem to provide water yield services and weakening its flow to human social systems due to external interference. This research provides strategic guidance for rationally allocating water resources in regional ecosystems and promoting ecological protection and collaborative development.

Background Chronic changes caused by a high‐fat diet (HFD) may be associated with weakened lung function in obese patients. However, few studies have focused on the role of senescent cells in HFD‐induced pulmonary fibrosis. This study aimed to determine whether (i) obesity causes the accumulation of aging cells in the lungs, (ii) p16 accumulation in aging epithelial cells or fibroblasts exacerbates long‐term HFD‐induced senescence‐associated pulmonary fibrosis (SAPF) and (iii) p16 deletion or clearance of aging cells ameliorates HFD‐induced SAPF through inactivation of the inflammasome and metabolic remodelling. Methods Twelve‐month old male mice of p16INK4a (hereafter p16) knockout (p16−/−) and wild‐type (WT), ApoE knockout (ApoE−/−) and ApoE−/−p16−/− were fed a HFD to induce obesity, and the effects of treatment with the senolytic drug ABT263 or the SGK1 specific inhibitor EMD638683 on fibrosis, inflammaging, gene expression, integrin‐inflammasome signalling and metabolism were examined. A549 and IMR‐90 cells were transduced with p16‐overexpressing adenovirus, and treated with palmitic and oleic acids (P&O) to induce steatosis in vitro. Results We found that long‐term HFD promoted the expression of p16 and the increase of senescent cells in the lung. P16 knockout or ABT263 treatment alleviated pulmonary fibrosis, the increase of senescent cells and senescence‐associated secretory phenotype (SASP) in HFD‐fed mice, as well as in P&O‐treated A549 and IMR‐90 cells. RNA sequencing and bioinformatics analyses revealed that p16 knockout inhibited activation of the integrin‐inflammasome pathway and cellular glycolysis. Mass spectrometry, co‐immunoprecipitation and GST pull‐down assays demonstrated that p16 bound to the N‐terminal of SGK1, thereby interfering with the interaction between the E3 ubiquitin ligase NEDD4L and SGK1, and subsequently inhibiting K48‐polyubiquitin‐dependent degradation of SGK1 mediated by the NEDD4L–Ubch5 complex. EMD638683 was found to alleviate HFD‐induced pulmonary fibrosis and activation of the integrin‐inflammasome pathway. Conclusion P16 accumulation promoted activation of integrin– inflammasome pathway and cell glycolysis by binding to the N– terminal of SGK1, intefering with the interaction between the E3 ubiquitin ligase NEDD4L and SGK1, thereby inhibiting K48– polyubiquitin– dependent degradation of SGK1 mediated by the NEDD4L–Ubch5 complex. ABT263 or EMD638683 could be used as potential drugs to treat pulmonary fibrosis in obese patients.

Aiming to resolve the problem where the reliability of gearbox bearings of wind turbines is easily affected by random impact, this paper puts forward a reliability evaluation method for the competitive failure of gearbox bearings of wind turbines considering the fault incubation point. Firstly, we use Weibull distribution to simulate the fault latent process of wind turbine gearbox bearings. Secondly, a natural degradation model of gearbox bearing is established based on the Wiener process. Then, we model the random impact arrival frequency and impact intensity through a homogeneous Poisson process and normal distribution, respectively. Finally, based on considering the fault incubation point, the natural degradation of the bearing, the instantaneous degradation caused by impact, and the decline in the impact resistance of the bearing, a reliability evaluation model of gearbox bearings of wind turbines is established. A high-speed bearing of a gearbox from a wind farm in northern China is selected for simulation analysis. The results show that the proposed method can better describe the reliability decline process of the gearbox bearings of wind turbines, which has a specific guiding significance for the maintenance of wind turbines.

BackgroundAcupuncture is a well-known treatment option for ischemic stroke recovery, but evidence of its effectiveness remains limited. This is a randomized controlled trial to evaluate the effectiveness of acupuncture treatment for ischemic stroke rehabilitation.MethodsRehabilitation training was provided to the control group. In acupuncture arm 1, these acupoints were derived from the ancient books, including GV20 (baihui), GV26 (shuigou), PC9 (zhongchong), ST6 (jiache), ST4 (dicang), LI15 (jianyu), LI11 (quchi), LI4 (hegu), GB30 (huantiao), GB31 (fengshi), GB34 (yanglingquan), and GB39 (xuanzhong). In acupuncture arm 2, the acupoints used were GV20 (baihui), PC6 (neiguan), LI11 (quchi), LI10 (shousanli), SJ5 (waiguan), LI4 (hegu), GB30 (huantiao), ST36 (zusanli), GB34 (yanglingquan), SP6 (sanyinjiao), ST41 (jiexi), and LR3 (taichong), which were extracted from Acupuncture and Moxibustion Science. After acupuncture, the needles were left in for 30 min and manually manipulated every 10 min. The three groups received treatment once a day, 5 times a week for 2 weeks. The primary outcome was the National Institutes of Health Stroke Scale (NIHSS), and the secondary outcomes were the Barthel Index (BI) and the Modified Ashworth Scale (MAS). Outcomes were measured in patients both before and after treatment.ResultsA total of 497 patients with ischemic stroke were randomized into either arm 1 (159 cases), arm 2 (173 cases), or the control group (165 cases). After 2 weeks of treatment, the NIHSS scores for arm 1 were lower than those of the control group (P = 0.017); the BI scores were higher in arm two than that in the control group at T2 (P = 0.016) and follow-up (P = 0.020). Additionally, there was no significant difference between arm one and the control group for either the BI scores or the MAS scores (P > 0.05) and no significant difference between arm two and the control group for the MAS scores or the NIHSS scores (P > 0.05).ConclusionThe clinical efficacy of arm 1 and arm 2 (acupuncture groups) was superior to that of the control group, but there was no difference between the effects of the two acupuncture groups.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifier: ChiCTR-IOR-16008627.

Having a high theoretical capacity density of 4200 mAh g−1, silicon has been highlighted as one of the most promising anode materials for lithium-ion batteries. Countless silicon-based materials have been proposed and reported in research articles, mostly synthesized using bottom-up methods. While the infamous volume expansion issue can be settled with the bottom-up processes, the complicated protocols and high cost leave a non-neglectable gap between laboratory-scale and mass production. The top-down ball-milling method is still favored by industrial suppliers because of its simplicity and cost-effectiveness, even with compromised electrochemical performances. This paper reviews the latest development of ball-milling-based silicon anode materials. Although the ball-milling process seems straightforward, the procedures and parameters influencing the product have hardly been discussed in research papers compared to the bottom-up ones. This paper reviews recent advances in ball-milling-based silicon anode materials, provides a material comparison, and discusses how ball milling can provide lithium-ion batteries with greater possibilities at a larger scale.

Fruit texture affects apples’ quality, consumer preference, and shelf life. The cell wall neutral sugar composition was reported to contribute to apples’ mechanical properties at harvest. However, the contributions of cell wall neutral sugar composition to apple texture loss during storage among different cultivars are still unclear. In this study, six cultivars of the apple fruit were stored at 25 °C for 60 days (i.e., rapid loss of texture: ‘Jiguan’, ‘Yindu’, and ‘Qinguan’; slow loss of texture: ‘Fuji’, ‘Huaguan’, and ‘Cripps pink’). The texture properties, physiological indicators, and expression of cell wall-related genes were investigated every 20 d. The results showed that apple cultivars with rapid texture loss showed a faster loss in flesh hardness and crispness, and a higher level of flesh tightness and pericarp break distance, than the cultivars with slow texture loss. Galactose content showed the closest association with the texture properties among the cell wall neutral sugar compositions. The rapid loss of galacturonic acid content and the expression of MdPG1 were higher in the cultivars with rapid texture loss than in those with slow texture loss. These results indicated that changes in cell wall neutral sugar composition contribute to apple texture loss during storage among cultivars.

The online strain acquisition is highly desired for structural monitoring of key equipment such as aircrafts or high-speed trains. However, there are still enormous challenges to monitor full-field strain in large area with arbitrary shape, especially when the non-contact approaches are not applicable. In this study, we firstly develop an optimization design principle for arbitrary-shape-adaptable sensor array with scalable circuit layout, and then a hierarchical printing strategy by direct-ink-writing is proposed to enable simultaneous monitoring in large-scale area or multiple domains. According to the design principle and printing strategy, the proof-of-concept sensor arrays (e.g. with 8 × 8 and 4 × 16 grids) are designed and printed by bottom-up hierarchies from the layered components (e.g. wires, filaments and isolation intervals) to the main arrays through distributed printing sub-arrays (4 × 4 grids). In particular, the strain field surrounding a hole is monitored in high-precision based on the present strain sensor. This work also provides insights of sensor array from adaptive design to high-efficient DIW-fabrication for other applications including wearable electronics, small-batch equipment and individual medical devices.

Biofilm-related bacteria show high resistance to antimicrobial treatments, posing a remarkable challenge to human health. Given bacterial dormancy and high expression of efflux pumps, persistent infections caused by mature biofilms are not easy to treat, thereby driving researchers toward the discovery of many anti-biofilm molecules that can intervene in early stage biofilms formation to inhibit further development and maturity. Compared with mature biofilms, early stage biofilms have fragile structures, vigorous metabolisms, and early attached bacteria are higher susceptibility to antimicrobials. Thus, removing biofilms at the early stage has evident advantages. Many reviews on anti-biofilm compounds that prevent biofilms formation have already been done, but most of them are based on compound classifications to introduce anti-biofilm effects. This review discusses the inhibitory effects of anti-biofilm compounds on early stage biofilms formation from the perspective of the mechanisms of action, including hindering reversible adhesion, reducing extracellular polymeric substances production, interfering in the quorum sensing, and modifying cyclic di-GMP. This information can be exploited further to help researchers in designing new molecules with anti-biofilm activity.

We previously reported that adiponectin (AD) promotes naïve T cell differentiation into Th17 cells and participates in synovial inflammation and the bone erosion process in patients with rheumatoid arthritis. Here, we use a T cell lineage adiponectin receptor 1 (AdipoR1) conditional knockout model to investigate the role of AdipoR1 in Th17 differentiation. RNA-sequencing (RNA-seq) demonstrated that AdipoR1 knockout reduced the expression of a variety of T cell related genes, with Rorc showing the greatest level of down-regulation. AdipoR1 deficiency inhibited Th17 cell differentiation in vitro and ameliorated joint inflammation in antigen-induced arthritis mice. Moreover, AdipoR1-deficent CD4+T cells displayed reduced Hypoxia-Inducible Factor-1α expression leading to glycolysis inhibition during naïve CD4+T cell differentiation into Th17 cells. We describe a novel function of AdipoR1 in regulating Th17 cell differentiation through modulating HIF-1α-dependent glycolysis.

Pulmonary fibrosis is a major cause of morbidity and mortality in systemic sclerosis (SSc) with no effective medication. Polyporus polysaccharide (PPS), extracted from Chinese herbs, has immune regulation, anticancer, antioxidant and antiinflammatory activities. This study aims to investigate antifibrotic effects of PPS. We show that PPS markedly ameliorates bleomycin-induced lung fibrosis in mice. Myofibroblasts are the effector cells responsible for excessive deposition of extracellular matrix (ECM) proteins in fibrotic diseases. In vitro evidence reveals that PPS exerts potent antifibrotic effects by inhibiting fibroblast-to-myofibroblast transition, suppressing ECM deposition, and repressing lung fibroblast proliferation and migration. We also find that PPS inhibits TGF-β1-induced Smad2/3 activating. This study is the first to demonstrate an antifibrotic role of PPS in lungs, thus warranting further therapeutic evaluation.

Low-cost and highly effective catalysts are crucial to the electrocatalytic hydrogen evolution reaction (HER). Among non-noble catalysts, molybdenum carbides are promising candidates because of their high reserves, stability, low cost, and structural diversity. In this work, we report a simple method to fabricate a hollow porous Mo2C@C nanoball through a hydrothermal preparation process of molybdenum precursors at high temperatures. Specifically, we have combined interfacial polymerization and the chelation effect to synthesize the Mo-polydopamine (Mo-PDA) precursor. As a result, Mo2C@C-3 only requires an ultralow Tafel slope (~55 mV dec−1) and low overpotential (η50 ≈ 167 mV) in a 0.5 M H2SO4 solution with long-term cycling stability. Besides, it also exhibits outstanding activity and stability under extensive HER testing in alkaline media. This study is promising for the development of advanced molybdenum carbide electrocatalysts toward electrochemical applications.

Recommendations by health professionals are important for vaccines that are not included in national schedules. This study explored health professionals’ perspectives on recommending non-scheduled (user-fee) childhood vaccinations in China, identifying key influences on professionals’ interactions with caregivers. We conducted individual semi-structured interviews with 20 health professionals from three provinces in China and analyzed data thematically using deductive and inductive coding. Health professionals from all three provinces were uncomfortable about being perceived to encourage parents to accept vaccines that incurred a fee. They provided information about non-scheduled vaccines but emphasized parental autonomy in decision-making. Rural parents were less aware of unscheduled vaccines and health professionals were more likely to encourage parents living in more affluent areas to consider these vaccines; varicella vaccine was preferred by parents as a way of preventing school absence. Economic incentives for unscheduled vaccines were given to staff at most study sites, although the amount given varied widely. These variations meant that staff receiving lower incentives were not motivated to promote non-scheduled vaccines if their workload was high; on the contrary, those receiving higher incentives were more likely to promote these vaccines. Health professionals need more guidance on how to recommend unscheduled vaccines in an informative, positive and appropriate manner. It is evident that parents’ awareness of these vaccines, and their economic circumstances, influence vaccinators recommendation practice. Economic incentives prompted health professionals to recommend non-scheduled vaccines; however, the application of such staff incentives varied widely in China. To adopt appropriate economic incentives, professional organizations should develop protocols for the use of incentives that account for their influence on recommendation practices. Suitable recommendation policy needs to balance basic salaries with performance-based incentives, consider overall workload, and include monitoring and evaluation of economic incentives.

Our study explored the effects of parental social integration on migrant children’s vaccination status in China. Using data obtained from the 2014 China Migrants Dynamic Survey, a total of 4915 participants were included in this study. Social integration was measured by economic, social, cultural, and internal identity. Univariate chi-square testing was used to calculate associations between all variables and migrant children’s vaccination status. Binary logistic regression was employed to calculate the impacts of social integration on migrant children’s vaccination status. In total, 94.7% of migrant children had complete vaccinations for their age. Migrants who had medical insurance, spoke the native language when communicating with locals, lived mainly with locals, and did not perceive discrimination were more likely to have their children completely vaccinated. Social integration was positively associated with migrant children’s vaccination status. Our study indicated that to improve vaccination coverage of migrant children, more policy support for migrant employment and housing, promotion of health services for migrants, and language support in health institutions is needed.

In a motor control system, the parameters tuning of speed and position controller depend on the value of the moment of inertia. A new moment of inertia identification scheme for permanent magnet motor system was proposed in this paper. This is an extension of the existing acceleration deceleration methods, which solves the large moment of inertia identification error caused by variable angular acceleration, large calculation error of inertia torque, and large measurement noise in the acceleration process. Based on the fact that the angular acceleration is not constant and the sampling signal is noisy, the integral chain differentiator was used to calculate the instantaneous angular acceleration at any time and suppress the sampling signal noise at the same time. The error function with instantaneous angular acceleration and inertia torque as parameters was designed to estimate the moment of inertia. In order to calculate the inertia torque accurately, viscous friction torque was considered in the calculation of inertia torque, and Kalman filter was used to estimate the total load torque to solve the problem of under rank of motor motion equation. Simulation and experimental results showed that the proposed method could effectively identify the moment of inertia in both noisy and noiseless environments.

In this paper, we introduce a new family of algebras Hn, which are generated by three generators x, y, z, with the following relations: (1) x2n = 1, y² = xy + y, xy = yx; and (2) z² = z, xz = zx = z, zy = 2z. First, it shows that Hn is a positively based algebra. Then, all the indecomposable modules of Hn are constructed. Additionally, it shows that the dimension of each indecomposable Hn-module is at most 2. Finally, all the left (right) cells and left (right) cell modules of Hn are described, and the decompositions of the decomposable left cell modules are also obtained. [ABSTRACT FROM AUTHOR]