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The collapse of immune homeostasis induces type 1 diabetes (T1D). In T1D, uncontrolled immune attacks against islet β cells reduce insulin secretion, resulting in hyperglycaemia and various complications. Type 1 regulatory (Tr1) cell therapy is a promising approach for the treatment of T1D. Tr1 cells are a subset of regulatory T (Treg) cells that are characterised by high interleukin-10 secretion and forkhead box protein P3 non-expression. Tr1 cells are reduced and have impaired function in patients with T1D. Immunotherapy is used to treat various diseases, and Treg cells have been applied to treat T1D in animal models and clinical trials. However, the safety and efficacy of Tr1 cells in treating diabetes and other diseases remain unclear. In this review, we aim to investigate the identification and biological function of Tr1 cells and related studies on immune diseases; additionally, we discuss the feasibility, limitations, and possible solutions of Tr1 cell therapy in T1D. This review shows that T1D is caused by an immune imbalance where defective Tr1 cells fail to control effector T cells, leading to the destruction of islet β cells. However, Tr1 cell therapy is safe and effective for other immune diseases, suggesting its potential for treating T1D.

The Low-Carbon City Pilot (LCCP) program in China is a climate policy implemented at the city level, and its impact on the development of corporate artificial intelligence (AI) remains to be studied. The LCCP program aims to promote low-carbon transformation in multiple Chinese cities and serves as a quasi-natural experiment to determine whether similar city-level climate policies can foster the development of corporate AI. This study employs a multi-period differences-in-differences (DID) approach to evaluate the impact of China’s LCCP program on the development of corporate AI. By redirecting attention from national-level policies to city-level initiatives, this study provides unique insights into the localized effects of climate policies on technological innovation within firms. The research findings indicate that the LCCP program has a significant promoting effect on the development of corporate AI. These results underscore the potential of city-level climate policies, such as the LCCP program, to drive advancements in corporate AI technologies. By demonstrating a positive correlation between the implementation of the LCCP program and increased levels of AI development within companies, the study provides valuable insights into the intersection of environmental policies and technological innovation. Policymakers and businesses can use these findings to guide the design and implementation of initiatives aimed at promoting sustainable economic growth through enhanced AI adoption. This study not only contributes to the academic discourse on environmental policy and technological innovation but also offers practical recommendations for achieving a balance between environmental sustainability and technological advancement.

Abstract Utilizing a dynamic computable general equilibrium (CGE) model, this paper critically assesses the potential distortions and efficacy of various revenue-neutral carbon emission trading schemes (ETSs) in China, through government subsidies and value-added tax (VAT) relief strategies aimed at achieving peak carbon emissions before 2030. The analysis reveals that reallocating market revenues to the production sector, either through government subsidies or VAT reductions, can feasibly attain carbon peaking before 2030, with minimal impact on GDP. Notably, both government subsidies and VAT cuts foster output growth in the oil, gas, and ETS-covered sectors. Moreover, directing carbon market revenue toward ETS-covered industries via VAT relief emerges as the most effective approach to reducing income disparities. In contrast, redistributing carbon market revenue to non-ETS-covered industries via VAT relief is found to be the least effective in promoting social equity. The study emphasizes that the reallocation of carbon market revenues to ETS-covered sectors is paramount. This strategy not only regulates the overall energy consumption effectively but also steers the nation towards a more sustainable and optimized energy consumption pattern. In light of these findings, this paper offers detailed insights and tailored policy recommendations, aiming to assist policymakers in striking a balance between environmental goals and economic and social imperatives.

Abstract Background Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease of nonspecific origin. This study used an RNA-Sequencing (RNA-Seq) approach to evaluate the transcriptomic landscape of a well-stratified treatment-naïve pediatric UC patient population by comparing them with healthy control children. The data were analyzed to evaluate the mechanisms driving UC-related intestinal inflammation and fibrosis. Methods Intestinal mucosal samples from five pediatric UC patients and five healthy controls were analyzed by RNA-Seq, and results were verified by qPCR. A CRISPR/Cas9 approach was used to knock out the expression of HLA-DRB5, and molecular biology techniques were used for additional mechanistic studies. Results In these analyses, 2290 genes were found to be differentially expressed between the UC and control samples, of which 1258 and 1032 were upregulated and downregulated, respectively. Gene Ontology analysis showed that these genes were enriched in extracellular matrix (ECM)-related processes and that 7 of 8 differentially expressed genes of interest (PIK3CD, IL1β, IL1α, TIMP1, MMP1, MMP12, COL6A3, and HLADRB5) were upregulated and involved in ECM-receptor interaction and inflammatory bowel disease-related pathways. Increased HLA-DRB5 expression driven by intestinal bacteria was found to promote IL-1α secretion, leading to intestinal inflammation and fibrosis, suggesting a possible target for the treatment of UC. Conclusion These data suggest that intestinal inflammation is present in pediatric UC patients for extended periods before the onset of symptoms, and intestinal fibrosis begins even during the early stages of UC. Intestinal bacteria were also found to trigger intestinal inflammation and fibrosis, with HLA-DRB5 playing a central role in this process.

BackgroundInnate lymphoid cells (ILCs), so far studied mostly in mouse models, are important tissue-resident innate immune cells that play important roles in the colorectal cancer microenvironment and maintain mucosal tissue homeostasis. Plasmacytoid dendritic cells (pDCs) present complexity in various tumor types and are correlated with poor prognosis. pDCs can promote HIV-1–induced group 3 ILC (ILC3) depletion through the CD95 pathway. However, the role of ILC3s in human colon cancer and their correlation with other immune cells, especially pDCs, remain unclear.MethodsWe characterized ILCs and pDCs in the tumor microenvironment of 58 colon cancer patients by flow cytometry and selected three patients for RNA sequencing.ResultsILC3s were negatively correlated, and pDCs were positively correlated, with cancer pathological stage. There was a negative correlation between the numbers of ILC3s and pDCs in tumor tissues. RNA sequencing confirmed the correlations between ILC3s and pDCs and highlighted the potential function of many ILC- and pDC-associated differentially expressed genes in the regulation of tumor immunity. pDCs can induce apoptosis of ILC3s through the CD95 pathway in the tumor-like microenvironment.ConclusionsOne of the interactions between ILC3s and pDCs is via the CD95 pathway, which may help explain the role of ILC3s in colon cancer.

Abstract Visceral leishmaniasis is a life-threatening parasitic disease, but current antileishmanial drugs have severe drawbacks. Antifungal azoles inhibit the activity of cytochrome P450 (CYP) 51 enzymes which are responsible for removing the C14α-methyl group of lanosterol, a key step in ergosterol biosynthesis in Leishmania. However, they exhibit varying degrees of antileishmanial activities in culture, suggesting the existence of unrecognized molecular targets. Our previous study reveals that, in Leishmania, lanosterol undergoes parallel C4- and C14-demethylation to form 4α,14α-dimethylzymosterol and T-MAS, respectively. In the current study, CYP5122A1 is identified as a sterol C4-methyl oxidase that catalyzes the sequential oxidation of lanosterol to form C4-oxidation metabolites. CYP5122A1 is essential for both L. donovani promastigotes in culture and intracellular amastigotes in infected mice. CYP5122A1 overexpression results in growth delay, increased tolerance to stress, and altered expression of lipophosphoglycan and proteophosphoglycan. CYP5122A1 also helps to determine the antileishmanial effect of antifungal azoles in vitro. Dual inhibitors of CYP51 and CYP5122A1 possess superior antileishmanial activity against L. donovani promastigotes whereas CYP51-selective inhibitors have little effect on promastigote growth. Our findings uncover the critical biochemical and biological role of CYP5122A1 in L. donovani and provide an important foundation for developing new antileishmanial drugs by targeting both CYP enzymes.

Abstract The prevalence of isolated systolic hypertension (ISH) has doubled between 2002−2005 and 2014 among the oldest‐old population in China. However, the prevalence and characteristics of ISH among the oldest‐old population in southwestern China remain less known. This study aimed to investigate the prevalence of ISH among the oldest‐old population in Chengdu and identify associated factors to provide valuable information for disease etiology and prevention. We recruited 1,312 participants aged over 80 years by using a stratified cluster sampling method between September 2015 and June 2016, from three districts (Jinjiang, Qingyang, and Longquanyi) of Chengdu, the largest city of southwest China. A structured questionnaire, anthropometric data, and blood pressure were collected according to the standard method. Blood pressure was measured three times by using a standardized mercury sphygmomanometer after a 10‐minute seated rest. Of 1312 participants, 53.0% (n = 695) had ISH. The prevalence of ISH in men and women was 54.7% and 51.3%, respectively, with no significant sex difference (P = .222). The prevalence of ISH increased with advanced age in men (P for trend = 0.029), 52.5% for the 80−84 years group, 55.2% for the 85−89 years group, and 70.4% for the 90–98 years group, respectively. Multivariable logistic regression analyses found that drinking (OR = 1.85, 95%CI = 1.26−2.71), being overweight (OR = 1.88, 95%CI = 1.19−2.96), and having a higher heart rate (OR = 0.66, 95%CI = 0.51−0.86) were associated with ISH. Stratified by sex, these three factors remained significant in men. Our work highlights that the burden of ISH is substantial among the oldest‐old population in southwestern China.

Abstract Introduction Tension-type headache (TTH) is common but challenging to manage due to limited effectiveness of conventional treatments. This study examines six complementary and alternative medicine (CAM) interventions through network meta-analysis to identify effective TTH management strategies. Methods We searched PubMed, Embase, Web of Science, Cochrane Library, OVID, CNKI, Wanfang, VIP, and CBM databases for randomized controlled trials on CAM for TTH treatment. Headache frequency and intensity were the primary outcomes. Methodological quality was evaluated on the basis of the Cochrane risk of bias tool. We used R software to conduct this Bayesian network meta-analysis. We used mean difference (MD) with 95% credible intervals (CI) to calculate the continuous outcomes and analyzed the percentages of the surface under the cumulative ranking (SUCRA) curve. Results In total, 32 randomized controlled trials (RCTs) with 2405 participants were analyzed. For reducing headache intensity, the network meta-analysis shows that acupuncture therapy combined with traditional Chinese medicine (AT_TCM), manual therapy (MT), psychological treatment (PT), and traditional Chinese medicine combined with acupuncture and manual therapy (TCM_AT_MT) are superior to Western medicine (WM). In the SUCRA curve, TCM_AT_MT is the best for reducing headache frequency (HF). Conclusions This review, assessed as low-quality evidence by GRADE, cautiously suggests potential benefits of PT over other CAM interventions for TTH and indicates TCM_AT_MT might better reduce HF. It proposes that combining CAM interventions could enhance outcomes. Due to the preliminary nature of these findings, further high-quality RCTs are essential to confirm these suggestions and provide clearer clinical guidance. PROSPERO Registration Number CRD42021252073.

Abstract Background Despite abundant evidence on the epidemiological risk factors of metabolic diseases related to hyperuricemia, there is still insufficient evidence regarding the nonlinear relationship between triglyceride-glucose (TyG) index and hyperuricemia. Thus, the purpose of this research is to clarify the nonlinear connection between TyG and hyperuricemia. Methods From 2011 to 2018, a cross-sectional study was carried out using data from the National Health and Nutrition Examination Survey (NHANES). This study had 8572 participants in all. TyG was computed as Ln [triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The outcome variable was hyperuricemia. The association between TyG and hyperuricemia was examined using weighted multiple logistic regression, subgroup analysis, generalized additive models, smooth fitting curves, and two-piecewise linear regression models. Results In the regression model adjusting for all confounding variables, the OR (95% CI) for the association between TyG and hyperuricemia was 2.34 (1.70, 3.21). There is a nonlinear and reverse U-shaped association between TyG and hyperuricemia, with a inflection point of 9.69. The OR (95% CI) before the inflection point was 2.64 (2.12, 3.28), and after the inflection point was 0.32 (0.11, 0.98). The interaction in gender, BMI, hypertension, and diabetes analysis was statistically significant. Conclusion Additional prospective studies are required to corroborate the current findings, which indicate a strong positive connection between TyG and hyperuricemia among adults in the United States.

BackgroundCurrent literature extensively covers the use of sphenopalatine ganglion stimulation (SPGs) in treating a broad spectrum of medical conditions, such as allergic rhinitis, cluster headaches, and strokes. Nevertheless, a discernible gap in the systematic organization and analysis of these studies is evident. This paper aims to bridge this gap by conducting a comprehensive review and analysis of existing literature on SPGs across various medical conditions.MethodsThis study meticulously constructed a comprehensive database through systematic computerized searches conducted on PubMed, Embase, CNKI, Wanfang, VIP, and CBM up to May 2022. The inclusion criteria encompassed randomized controlled trials (RCTs) published in either Chinese or English, focusing on the therapeutic applications of SPGs for various medical conditions. Both qualitative and quantitative outcome indicators were considered eligible for inclusion.ResultsThis comprehensive study reviewed 36 publications, comprising 10 high-quality, 23 medium-quality, and three low-quality articles. The study investigated various diseases, including allergic rhinitis (AR), ischemic strokes (IS), cluster headache (CH), primary trigeminal neuralgia (PTN), pediatric chronic secretory otitis (PCSO), refractory facial paralysis (RFP), chronic tension-type headache (CTTH), as well as the analysis of low-frequency sphenopalatine ganglion stimulation (LF-SPGs) in chronic cluster headache (CCH) and the impact of SPGs on Normal nasal cavity function (NNCF). SPGs demonstrate efficacy in the treatment of AR. Regarding the improvement of rhinoconjunctivitis quality of life questionnaire (RQLQ) scores, SPGs are considered the optimal intervention according to the SUCRA ranking. Concerning the improvement in Total Nasal Symptom Score (TNSS), Conventional Acupuncture Combined with Tradiational Chinese Medicine (CA-TCM) holds a significant advantage in the SUCRA ranking and is deemed the best intervention. In terms of increasing Effective Rate (ER), SPGs outperformed both conventional acupuncture (CA) and Western Medicine (WM; P < 0.05). In the context of SPGs treatment for IS, the results indicate a significant improvement in the 3-month outcomes, as evaluated by the modified Rankin Scale (mRS) in the context of Cerebral Cortical Infarction (CCI; P < 0.05). In the treatment of CH with SPGs, the treatment has been shown to have a statistically significant effect on the relief and disappearance of headaches (P < 0.05). The impact of SPGs on NNCF reveals statistically significant improvements (P < 0.05) in nasal airway resistance (NAR), nasal cavity volume (NCV), exhaled nitric oxide (eNO), substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY). SPGs treatments for PCSO, RFP, and CTTH, when compared to control groups, yielded statistically significant results (P < 0.05).ConclusionSPGs demonstrate significant effectiveness in the treatment of AR, IS, and CH. Effective management of CCH may require addressing both autonomic dysregulation and deeper neural pathways. However, additional high-quality research is essential to clarify its effects on NNCF, PTN, PCSO, RFP, and CTTH.Systematic Review RegistrationPROSPERO, identifier CRD42021252073, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=312429.

This study aims to examine the congruence of trade openness with regards to encouraging pervasive usage of green energy sources and the nexus among environmental degradation, economic development, oil prices, and green energy consumption (GEC). The study utilizes advanced panel data techniques, including the Westerlund cointegration test, Augmented Mean Group (AMG) estimator, Pooled Mean Group (PMG) estimator, and the Dumitrescu and Hurlin (DH) causality test, to examine the aforementioned relationships. The findings of the AMG and PMG estimators indicate that environmental degradation has a negative impact on GEC, whereas oil prices and economic development have a positive effect on GEC.

BackgroundThere is a correlation between obesity and 25-hydroxyvitamin D (25OHD) that tends to be negative. However, this relationship varies among different races. In this study, Asian adults with and without obesity were compared in terms of their levels of 25OHD.MethodsWe carried out a cross-sectional analysis on 2664 non-Hispanic Asian adults who participated in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018. To examine the connection between obese status, body mass index (BMI), waist circumference (WC) and weight, and 25OHD, we ran multivariate linear regression models and multivariate logistic regression models.ResultsAfter adjusting for all confounding factors, obesity status shows a significant positive correlation with vitamin D deficiency (model 3: OR = 2.318, 95% CI:1.317, 4.082). This positive correlation remains significant in males (males: OR = 2.713, 95% CI: -13.398, 5.217). In all three models, a negative association was observed between obesity status and 25OHD (model 1: β = -4.535, 95% CI: -6.987, -2.083; model 2 β = -4.249, 95% CI: -6.549, -2.039; model 3 β = -1.734, 95% CI: -7.285, 3.816). After controlling for covariates, there was a significant negative correlation between WC and 25OHD when stratified by gender and obesity status in both males with and without obesity (males with obesity: β = -1.461, 95% CI: -2.485, -0.436; males without obesity: β = -0.855. 95% CI: -1.499, -0.210). In males with obesity, there was a very strong positive connection between body weight and 25OHD (β = 0.912, 95% CI: 0.227, 1.597). In addition, neither gender's obese individuals showed a significant link between BMI and 25OHD.ConclusionThis study demonstrated a positive correlation between obesity and vitamin D deficiency and a negative correlation between obesity and 25OHD in Asian American adults. Additionally, among male obese individuals, there was a significant negative correlation between WC and 25OHD, an observation that needs to be validated in further prospective studies.

A power clamp circuit, which has good immunity to false trigger under fast power-on conditions with a 20 ns rising edge, is proposed in this paper. The proposed circuit has a separate detection component and an on-time control component which enable it to distinguish between electrostatic discharge (ESD) events and fast power-on events. As opposed to other on-time control techniques, instead of large resistors or capacitors, which can cause a large occupation of the layout area, we use a capacitive voltage-biased p-channel MOSFET in the on-time control part of the proposed circuit. The capacitive voltage-biased p-channel MOSFET is in the saturation region after the ESD event is detected, which can serve as a large equivalent resistance (~106 Ω) in the structure. The proposed power clamp circuit offers several advantages compared to the traditional circuit, such as having at least 70% area savings in the trigger circuit area (30% area savings in the whole circuit area), supporting a power supply ramp time as fast as 20 ns, dissipating the ESD energy more cleanly with little residual charge, and recovering faster from false triggers. The rail clamp circuit also offers robust performance in an industry-standard PVT (process, voltage, and temperature) space and has been verified by the simulation results. Showing good performance of human body model (HBM) endurance and high immunity to false trigger, the proposed power clamp circuit has great potential for application in ESD protection.

Single-event gate-rupture (SEGR) in the trench vertical double-diffused power MOSFET (VDMOS) occurs at a critical bias voltage during heavy-ion experiments. Fault analysis demonstrates that the hot spot is located at the termination of the VDMOS, and the gate oxide in the termination region has been damaged. The SEGR-hardened termination with multiple implantation regions is proposed and simulated using the Sentaurus TCAD. The multiple implantation regions are introduced, leading to an increase in the distance between the gate oxide and the hole accumulation region, as well as a decrease in the resistivity of the hole conductive path. This approach is effective in reducing the electric field of the gate oxide to below the calculated critical field, and results in a lower electric field than the conventional termination.

With the popularity of 5G technology and electric vehicles, many countries around the world have adopted 5G technology to build sustainable smart city systems, and intelligent transportation is an important part of smart cities. From the perspective of 5G technology innovation bringing changes to traditional industries, in this paper, we analyze the mechanism by which 5G technology drives the transformation and upgrading of the electric vehicle industry. Based on the changes brought by 5G technology to the three industries of agriculture, industry and services, we analyzed the transformation of business models brought about by 5G with respect to electric vehicle operation. Furthermore, we analyzed the data of a 5G real-time system of electric vehicle and traffic operating in Nanjing, China, for a month in 2021, with a total of 10,610 electric vehicles and 1,048,575 cases to model the modes of electric vehicle operation associated with the platform. Based on the frequency density method, we identified three typical operating modes of urban electric vehicles: private electric vehicle use instead of walking accounts for 24.8%, passenger vehicles (Uber/Didi and taxi) account for 64.4% and logistic distribution electric vehicles account for 10.8%. We developed a method to automatically identify the operating mode of electric vehicles using data from a 5G real-time electric vehicle traffic platform, which provide a reference for the operation of electric vehicles associated with the platform. This work also provides data that can be used to support the establishment of models for the commercial operation of charging points.

The relationship between green technology innovation and corporate financial performance has gained considerable traction in academics and businesses. However, there is limited overall bibliometric analysis on this topic. To meet the research need, this study, using Citespace (Citespace5.8r3 version, ChaomMei Chen, Philadelphia), performed the bibliometric analysis of the relationship between green technology innovation and corporate financial performance from 2007 to 2021, with 251 academic papers published in the Web of Science databases being analyzed, thus identifying the research hotspots and trends. The results showed that: (i) the number of publications has moved from slow to rapid growth and is expected to ramp up further; (ii) only a small collaboration network has been formed among the authors; (iii) institutions’ work operates relatively independently. There is still more room for inter-institutional or cross-discipline cooperation against geographical regions. However, there is a strong network of cooperation among countries. China performs best in this research area, followed by Spain and the UK; (iv) several significant co-citation relationships are also formed in the literature network. The burst literature on green innovation, product innovation, and financial performance is considered a research hotspot; and (v) “green innovation”, “corporate performance”, “legitimacy”, “environmental disclosure”, and “corporate sustainability” have become trends in research. Our results provide academics and practitioners with a robust roadmap on the relationship between green technology innovation and corporate financial performance.

Industrial green technology innovation has become an important content in achieving high-quality economic growth and comprehensively practicing the new development concept in the new era. This paper measures the efficiency of industrial green technology innovation and regional differences based on Chinese provincial panel data from 2005 to 2018, using a combination of the super efficiency slacks-based measure (SBM) model for considering undesirable outputs and the Dagum Gini coefficient method, and discusses and analyses the factors influencing industrial green technology innovation efficiency by constructing a spatial econometric model. The results show that: firstly, industrial green technology innovation efficiency in China shows a relatively stable development trend, going through three stages: “stationary period”, “recession period” and “growth period”. However, the efficiency gap between different regions is obvious, specifically in the eastern > central > western regions of China, and the industrial green technology efficiency innovation in the central and western regions is lower than the national average. Secondly, regional differences in the efficiency of industrial green technology innovation in China are evident but tend to narrow overall, with the main reason for the overall difference being regional differences. In terms of intra-regional variation, variation within the eastern region is relatively stable, variation within the central region is relatively low and shows an inverted ‘U’ shaped trend, and variation within the western region is high and shows a fluctuating downward trend. Thirdly, the firm size, government support, openness to the outside world, environmental regulations and education levels contribute to the efficiency of industrial green technology innovation. In addition, the industrial structure hinders the efficiency of industrial green technology innovation, and each influencing factor has different degrees of spatial spillover effects.

Piperine is a kind of natural functional active components with spicy flavor and varies pharmacology effects. It has wide application in the food and medicine industries. However, the solubility of piperine is low, and it was easy to be transformed or degraded during the conditions of acid, alkali, light, heat and oxygen which lead to the vanish of its function. In order to enhance the stability of piperine, the nanotechnology was utilized to fabricate the delivery carrier of piperine. In this paper, the latest research progress of piperine nanoparticles was reviewed by summarizing domestic and foreign literature. The characteristics, preparation methods, preparation materials and stability of nanoparticle delivery carriers were systematically discussed. Finally, the present problems and future development of piperine delivery carrier were analyzed and forecasted in order to provide a reference for profound process and study of piperine.