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Abstract Background This study explored the influence of type 2 diabetes and impaired glucose tolerance (IGT) on the risk of the multimorbidity cluster of cardiovascular disease (CVD) and cancer. Methods A total of 1629 participants in the Da Qing Diabetes Prevention Outcome Study were recruited in the present analysis, including normal glucose tolerance (NGT, N = 492), IGT (N = 540), and newly diagnosed type 2 diabetes (N = 597) groups. Cox proportional hazards analyses were performed to assess the relationship between NGT, IGT, and newly diagnosed type 2 diabetes and the risk of the multimorbidity cluster of CVD and cancer. Results The incidence rates for multimorbidity cluster CVD and cancer were 1.25, 3.17, and 3.23 per 1000 person-years in people with NGT, IGT, and the newly diagnosed type 2 diabetes groups, respectively, over 34-year follow-up. Cox analysis revealed that diabetes status (as time-dependent variable) was significantly associated with the subsequent increased risk of multimorbidity cluster of CVD and cancer compared with non-diabetes (hazard ratios [HR] = 2.55, 95% confidence interval [CI] 1.51–4.31) after adjustment of potential confounders. Similar analysis showed that this risk was significantly higher in the IGT and newly diagnosed type 2 diabetes groups compared with NGT, with HR of 3.28 (95% CI 1.83–5.87) and HR of 3.90 (95% CI 2.14–7.09), respectively. Whereas compared diabetes with IGT group, this risk was not significantly different. Conclusions Similar to newly diagnosed type 2 diabetes, IGT is significantly associated with an increased risk of the multimorbidity cluster of CVD and cancer compared with NGT. This finding highlights the urgent need for an active detection of IGT and effective prevention and management of diabetes.

BackgroundCognition disorders not only lead to adverse health consequences but also contribute to a range of socioeconomic challenges and diminished capacity for performing routine daily activities. In the digital era, understanding the impact of digital exclusion on cognitive function is crucial, especially in developing countries. ObjectiveThis study aimed to evaluate the association between digital exclusion and cognitive function among elderly populations in developing countries. MethodsUsing data from CHARLS (China Health and Retirement Longitudinal Study) from 2011 to 2020 and MHAS (Mexican Health & Aging Study) from 2012 to 2021, we defined digital exclusion as self-reported absence from the internet. Cognitive function was assessed through 5 tests: orientation, immediate verbal recall, delayed verbal recall, serial 7s, and figure recall. Cognitive function was assessed in 2 categories: worse cognition (a categorical variable that classifies cognition as either better or worse compared to the entire cohort population) and cognitive scores (a continuous variable representing raw cognitive scores across multiple follow-up waves). Logistic regression analyses and generalized estimating equation (GEE) analyses were used to examine the relationship between cognitive function and digital exclusion, adjusting for potential confounders, including demographics, lifestyle factors, history of chronic diseases, basic activities of daily living (BADL) disability, instrumental activities of daily living (IADL) disability, and basic cognitive abilities. ResultsAfter excluding participants with probable cognitive impairment at baseline and those who did not have a complete cognitive assessment in any given year (ie, all tests in the cognitive assessment must be completed in any follow-up wave), a total of 24,065 participants in CHARLS (n=11,505, 47.81%) and MHAS (n=12,560, 52.19%) were included. Of these, 96.78% (n=11,135) participants in CHARLS and 70.02% (n=8795) in MHAS experienced digital exclusion. Adjusted logistic regression analyses revealed that individuals with digital exclusion were more likely to exhibit worse cognitive performance in both CHARLS (odds ratio [OR] 2.04, 95% CI 1.42-2.99; P.05). The fully adjusted mean differences in global cognitive scores between the 2 groups were 0.98 (95% CI 0.70-1.28; P

Abstract Aims We intended to characterize the superiority of triglyceride glucose‐body mass index (TyG‐BMI) in predicting type 2 diabetes mellitus (T2DM) compared with triglyceride glucose (TyG) and homeostatic model assessment for insulin resistance (HOMA‐IR). Methods A total of 699 nondiabetic participants in the Da Qing IGT and Diabetes Study were involved in the present analysis and classified according to the median of baseline TyG‐BMI, namely the G1 (low TyG‐BMI) and G2 (high TyG‐BMI) groups. Information on developing diabetes was assessed from 1986 to 2020. Results During the 34‐year follow‐up, after adjustment for confounders, the G2 group had a higher risk of developing type 2 diabetes than the G1 group (hazard ratio [HR]: 1.92, 95% confidence interval [CI]: 1.51–2.45, p 0.05). Time‐dependent receiver operator characteristics curves suggested that TyG‐BMI exhibited higher predictive ability than TyG (6‐year: area under the curve [AUC]TyG‐BMI vs. AUCTyG, 0.78 vs. 0.70, p = 0.03; 34‐year: AUCTyG‐BMI vs. AUCTyG, 0.79 vs. 0.73, p = 0.04) and HOMA‐IR (6‐year: AUCTyG‐BMI vs. AUCHOMA‐IR, 0.78 vs. 0.70, p = 0.07; 34‐year: AUCTyG‐BMI vs. AUCHOMA‐IR, 0.79 vs. 0.71, p = 0.04) in both short and long terms, and the thresholds of TyG‐BMI to predict type 2 diabetes were relatively stable (195.24–208.41) over the 34‐year follow‐up. Conclusions In this post hoc study, higher TyG‐BMI was associated with an increased risk of type 2 diabetes and demonstrated better predictability than TyG and HOMA‐IR, favoring the application of TyG‐BMI as a potential tool for evaluating the risk of type 2 diabetes in clinical practice.

With the atypical rise of Mycoplasma pneumoniae infection (MPI) in 2023, prompt studies are needed to determine the current epidemic features and risk factors with emerging trends of MPI to furnish a framework for subsequent investigations. This multicentre, retrospective study was designed to analyse the epidemic patterns of MPI before and after the COVID-19 pandemic, as well as genotypes and the macrolide-resistance-associated mutations in MP sampled from paediatric patients in Southern China. Clinical data was collected from 1,33,674 patients admitted into investigational hospitals from 1 June 2017 to 30 November 2023. Metagenomic next-generation sequencing (mNGS) data were retrieved based on MP sequence positive samples from 299 paediatric patients for macrolide-resistance-associated mutations analysis. Pearson's chi-squared test was used to compare categorical variables between different time frames. The monthly average cases of paediatric common respiratory infection diseases increased without enhanced public health measures after the pandemic, especially for influenza, respiratory syncytial virus infection, and MPI. The contribution of MPI to pneumoniae was similar to that in the outbreak in 2019. Compared to mNGS data between 2019–2022 and 2023, the severity of MP did not grow stronger despite higher rates of macrolide-resistance hypervariable sites, including loci 2063 and 2064, were detected in childhood MP samples of 2023. Our findings indicated that ongoing surveillance is necessary to understand the impact of post pandemic on MP transmission disruption during epidemic season and the severity of clinical outcomes in different scenarios.

ABSTRACTThe ever-growing use of nature-derived materials creates exciting opportunities for novel development in various therapeutic biomedical applications. Living cells, serving as the foundation of nanoarchitectonics, exhibit remarkable capabilities that enable the development of bioinspired and biomimetic systems, which will be explored in this review. To understand the foundation of this development, we first revisited the anatomy of cells to explore the characteristics of the building blocks of life that is relevant. Interestingly, animal cells have amazing capabilities due to the inherent functionalities in each specialized cell type. Notably, the versatility of cell membranes allows red blood cells and neutrophils’ membranes to cloak inorganic nanoparticles that would naturally be eliminated by the immune system. This underscores how cell membranes facilitate interactions with the surroundings through recognition, targeting, signalling, exchange, and cargo attachment. The functionality of cell membrane-coated nanoparticles can be tailored and improved by strategically engineering the membrane, selecting from a variety of cell membranes with known distinct inherent properties. On the other hand, plant cells exhibit remarkable capabilities for synthesizing various nanoparticles. They play a role in the synthesis of metal, carbon-based, and polymer nanoparticles, used for applications such as antimicrobials or antioxidants. One of the versatile components in plant cells is found in the photosynthetic system, particularly the thylakoid, and the pigment chlorophyll. While there are challenges in consistently synthesizing these remarkable nanoparticles derived from nature, this exploration begins to unveil the endless possibilities in nanoarchitectonics research.

Abstract Background This study aimed to investigate the potential differences in the influence of impaired glucose tolerance (IGT) with and without metabolic syndrome (MetS) on cardiovascular (CV) events and mortality. Methods Participants having IGT with MetS (IGT_MetS), those having IGT without MetS (IGT_non_MetS), and those having normal glucose tolerance (NGT) without MetS (NGT_non_MetS) (N = 246, N = 294, and N = 471, respectively) were included in this study. Cox proportional hazards regression was used to examine the relationship among these three groups and CV events and mortality. Results Over the 30‐year follow‐up period, 57 (12.1%) participants having NGT_non_MetS, 55 (18.71%) with IGT_non_MetS, and 74 (30.08%) with IGT_MetS experienced CV mortality. After adjusting for risk factors, the hazard ratios for CV mortality were 2 (95% confidence interval [CI], 1.38–2.91) for the IGT_non_MetS group and 2.96 (95% CI, 2.09–4.19) for the IGT_MetS group, compared with the NGT_non_MetS group. Similar patterns were observed for CV events, with hazard ratios of 1.49 (95% CI, 1.19–1.88) for the IGT_non_MetS group and 1.97 (95% CI, 1.58–2.47) for the IGT_MetS group. Sensitivity analysis revealed that the hazard ratios of the IGT_non_MetS and IGT_MetS groups indicated a higher risk of all‐cause mortality, myocardial infarction events or myocardial infarction mortality, and stroke events or stroke mortality compared with that of the NGT_non_MetS group. Conclusion IGT_non_MetS increased the risk of CV mortality and events. Furthermore, when it occurred in conjunction with MetS, it further increased the risk of CV mortality and events. This suggested that active intervention is required.

BackgroundThe association between years of non-diabetes status after diagnosis of impaired glucose tolerance (IGT) and the risk of long-term death and cardiovascular outcomes needed to be clarified.Methods and findingsIn this post hoc analysis, we included 540 individuals with IGT who participated in the original Da Qing Diabetes Prevention Study (DQDPS). In the DQDPS, all participants were diagnosed with IGT by a 75 g oral glucose tolerance test and randomized to intervention or control groups with a 6-year lifestyle intervention trial. After the completion of the trial, death, cardiovascular events, and microvascular complications were monitored over a 30-year follow-up. In this post hoc analysis, the Cox analysis assessed the extended risk of these outcomes in individuals who either remained non-diabetes status or progressed to diabetes at the end of 2, 4, and 6 years after diagnosis of IGT. In all participants, the difference in the cumulative incidence rate of the outcomes between the diabetes and non-diabetes group gradually increased over 30 years. Compared with the diabetes group, a significantly lower risk of all-cause death (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.57 to 0.97, p = 0.026), cardiovascular events (HR: 0.63; 95% CI: 0.49 to 0.82, p < 0.001), and microvascular complications (HR: 0.62; 95% CI: 0.45 to 0.86, p = 0.004) first emerged in individuals who remained non-diabetes at the 4 years visit, whereas the significant risk reduction in cardiovascular death was first observed at the end of 6 years (HR: 0.56; 95% CI: 0.39 to 0.81, p = 0.002) after adjustment for age, sex, smoking status, BMI, systolic blood pressure, blood glucose, total cholesterol, intervention, and medications (including insulin plus oral hypoglycaemics, antihypertensives, and lipid-lowering agents). The results in the original intervention group alone were similar to the whole group. The main limitations of our study are the limited number of participants and the sole ethnicity of the Chinese population.ConclusionsIn this study, we observed that maintaining several years of non-diabetes status after IGT diagnosis was associated with a significant reduction in long-term risk of death and vascular complications, and for most of these outcomes, maintaining at least 4 years of non-diabetes status may be needed to achieve a significant risk reduction.

Abstract Background Higher levels of palmitoyl sphingomyelin (PSM, synonymous with sphingomyelin 16:0) are associated with an increased risk of cardiovascular disease (CVD) in people with diabetes. Whether circulating PSM levels can practically predict the long-term risk of CVD and all-cause death remains unclear. This study aimed to investigate whether circulating PSM is a real predictor of CVD death in Chinese adults with or without diabetes. Methods A total of 286 and 219 individuals with and without diabetes, respectively, from the original Da Qing Diabetes Study were enrolled. Blood samples collected in 2009 were used as a baseline to assess circulating PSM levels. The outcomes of CVD and all-cause death were followed up from 2009 to 2020, and 178 participants died, including 87 deaths due to CVD. Cox proportional hazards regression was used to estimate HRs and their 95% CIs for the outcomes. Results Fractional polynomial regression analysis showed a linear association between baseline circulating PSM concentration (log-2 transformed) and the risk of all-cause and CVD death (p 0.05), in all participants after adjustment for confounders. When the participants were stratified by PSM-tertile, the highest tertile, regardless of diabetes, had a higher incidence of CVD death (41.5 vs. 14.7 and 22.2 vs. 2.9 per 1000 person-years in patients with and without diabetes, respectively, all log-rank p

Abstract High recurrence and metastasis rates and poor prognoses are the major challenges of current cancer therapy. Mounting evidence suggests that cancer stem cells (CSCs) play an important role in cancer development, chemoradiotherapy resistance, recurrence, and metastasis. Therefore, targeted CSC therapy has become a new strategy for solving the problems of cancer metastasis and recurrence. Since the properties of CSCs are regulated by the specific tumour microenvironment, the so-called CSC niche, which targets crosstalk between CSCs and their niches, is vital in our pursuit of new therapeutic opportunities to prevent cancer from recurring. In this review, we aim to highlight the factors within the CSC niche that have important roles in regulating CSC properties, including the extracellular matrix (ECM), stromal cells (e.g., associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and mesenchymal stem cells (MSCs)), and physiological changes (e.g., inflammation, hypoxia, and angiogenesis). We also discuss recent progress regarding therapies targeting CSCs and their niche to elucidate developments of more effective therapeutic strategies to eliminate cancer.

People’s emotional life is increasingly interwoven with social media. Against the background of the COVID-19 pandemic and lockdown in China, this study investigated social media affordances enacted during people’s emotion regulation processes. By analyzing in-depth interviews with 27 Shanghai residents going through a 2-month lockdown, we identified intersections between social media affordances and different emotion regulation processes: selectivity and intrapersonal emotion regulation; visibility and emotional self-presentation; bandwidth and interpersonal emotion regulation; connectivity and collective emotion regulation. This study extended our knowledge of mediated emotion regulation processes and enriched our understanding of the dynamic relations between users, media technologies, and emotional and social contexts.

Weaned stress may damage the tissue development, barrier function, and balance of microbiota of gut, resulting in the diarrhea and reduced growth performance of piglets. Probiotics with excellent characteristics can enhance the resistance of piglets to weaned stress. Under a poor sanitary condition, the Limosilactobacillus reuteri (L. reuteri) SLZX19-12 was supplemented to check its effects for piglets. Results showed that supplementation of L. reuteri significantly decreased the diarrhea incident, improved the growth performance, and enhanced the barrier integrity of gut. In ileum, L. reuteri decreased inflammation by NFκB p65 pathway, increased propionate, TCDCA, and THDCA contents, and regulated microbiota. In colon, L. reuteri decreased the inflammation by NFκB p65 pathway, reduced DCA content, and regulated microbiota. Therefore, the supplementation of L. reuteri may alleviate weaned stress by improving immune function and regulating the gut microbiota in piglets.

Abstract Background A significant proportion of septic patients with acute lung injury (ALI) are recognized late due to the absence of an efficient diagnostic test, leading to the postponed treatments and consequently higher mortality. Identifying diagnostic biomarkers may improve screening to identify septic patients at high risk of ALI earlier and provide the potential effective therapeutic drugs. Machine learning represents a powerful approach for making sense of complex gene expression data to find robust ALI diagnostic biomarkers. Methods The datasets were obtained from GEO and ArrayExpress databases. Following quality control and normalization, the datasets (GSE66890, GSE10474 and GSE32707) were merged as the training set, and four machine learning feature selection methods (Elastic net, SVM, random forest and XGBoost) were applied to construct the diagnostic model. The other datasets were considered as the validation sets. To further evaluate the performance and predictive value of diagnostic model, nomogram, Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) were constructed. Finally, the potential small molecular compounds interacting with selected features were explored from the CTD database. Results The results of GSEA showed that immune response and metabolism might play an important role in the pathogenesis of sepsis-induced ALI. Then, 52 genes were identified as putative biomarkers by consensus feature selection from all four methods. Among them, 5 genes (ARHGDIB, ALDH1A1, TACR3, TREM1 and PI3) were selected by all methods and used to predict ALI diagnosis with high accuracy. The external datasets (E-MTAB-5273 and E-MTAB-5274) demonstrated that the diagnostic model had great accuracy with AUC value of 0.725 and 0.833, respectively. In addition, the nomogram, DCA and CIC showed that the diagnostic model had great performance and predictive value. Finally, the small molecular compounds (Curcumin, Tretinoin, Acetaminophen, Estradiol and Dexamethasone) were screened as the potential therapeutic agents for sepsis-induced ALI. Conclusion This consensus of multiple machine learning algorithms identified 5 genes that were able to distinguish ALI from septic patients. The diagnostic model could identify septic patients at high risk of ALI, and provide potential therapeutic targets for sepsis-induced ALI.

Sorghum (Sorghum bicolor), the fifth most important cereal crop globally, serves as a staple food, animal feed, and a bioenergy source. Paclobutrazol-Resistance (PRE) genes play a pivotal role in the response to environmental stress, yet the understanding of their involvement in pest resistance remains limited. In the present study, a total of seven SbPRE genes were found within the sorghum BTx623 genome. Subsequently, their genomic location was studied, and they were distributed on four chromosomes. An analysis of cis-acting elements in SbPRE promoters revealed that various elements were associated with hormones and stress responses. Expression pattern analysis showed differentially tissue-specific expression profiles among SbPRE genes. The expression of some SbPRE genes can be induced by abiotic stress and aphid treatments. Furthermore, through phytohormones and transgenic analyses, we demonstrated that SbPRE4 improves sorghum resistance to aphids by accumulating jasmonic acids (JAs) in transgenic Arabidopsis, giving insights into the molecular and biological function of atypical basic helix-loop-helix (bHLH) transcription factors in sorghum pest resistance.

Abstract Aim To learn the functional fitness levels in older adults with diabetes combined with sarcopenia and/or frailty. Design A cross‐sectional investigation study. Methods A total of 205 participants with type 2 diabetes were recruited from September 2019 to August 2020. All patients underwent diagnostic screening for sarcopenia and frailty, and were divided into combined group (the patients who had sarcopenia and/or frailty) and non‐combined group (the patient who had no sarcopenia and/or frailty). The diagnostic criteria for sarcopenia applied was proposed by the Asian Working Group on Sarcopenia in 2019 and frailty status was assessed using FRAIL Scale. Functional fitness was measured using the Senior Fitness Test and compared between combined and non‐combined groups. Biochemical data of blood routine, glycolipid, and hepatorenal function tests were acquired from medical records. Logistic regression analysis was applied to explore the factors associated with the sarcopenia and/or frailty in the older adults with diabetes. Results Compared with non‐combined group, the participants in combined group exhibited shorter 6‐min walk distance, fewer repetitions of arm curls and chair stands, smaller back scratch and chair sit‐and‐reach values, and longer time in the 8‐ft up‐and‐go test. The patients in the combined group had significantly lower level of red blood cell, haemoglobin, haematocrit, and higher level of platelet and blood urea nitrogen. Apart from calf circumference, physical activity, and insulin injection treatment, 6‐min walk distance was the factor associated with diabetes combined with sarcopenia and/or frailty.

The invasion of pathogens derived from diet or the environment triggers intestinal inflammation, which is a result of the host intestinal barrier damage and immune dysfunction, such as the decrease of host defense peptides (HDPs) and inhibition of cell proliferation. Herein, the siRNA interference demonstrated that a critical lysozyme, which was mainly induced by dietary supplementations of sodium butyrate and forskolin, improved cell proliferation by inhibiting p38 MAPK and JNK signaling pathways and reinforced the intestinal barrier. Moreover, we established a mouse model of intestinal inflammation with Citrobacter rodentium (C. rodentium). It was found that NaBu and FSK stimulated intestinal epithelial proliferation to repair barrier damage, and performed stronger disease resistance to C. rodentium infection on account of the lysozyme upregulation in colon. Therefore, this study revealed that NaBu and FSK prevented or alleviated the development of foodborne infections by promoting lysozyme expression, which may be mediated by the effect of lysozyme on promoting cell proliferation and improving barrier function.

Abstract Linear local tangent space alignment (LLTSA) is a classical dimensionality reduction method based on manifold. However, LLTSA and all its variants only consider the one-way mapping from high-dimensional space to low-dimensional space. The projected low-dimensional data may not accurately and effectively “represent” the original samples. This paper proposes a novel LLTSA method based on the linear autoencoder called LLTSA-AE (LLTSA with Autoencoder). The proposed LLTSA-AE is divided into two stages. The conventional process of LLTSA is viewed as the encoding stage, and the additional and important decoding stage is used to reconstruct the original data. Thus, LLTSA-AE makes the low-dimensional embedding data “represent” the original data more accurately and effectively. LLTSA-AE gets the recognition rates of 85.10, 67.45, 75.40 and 86.67% on handwritten Alphadigits, FERET, Georgia Tech. and Yale datasets, which are 9.4, 14.03, 7.35 and 12.39% higher than that of the original LLTSA respectively. Compared with some improved methods of LLTSA, it also obtains better performance. For example, on Handwritten Alphadigits dataset, compared with ALLTSA, OLLTSA, PLLTSA and WLLTSA, the recognition rates of LLTSA-AE are improved by 4.77, 3.96, 7.8 and 8.6% respectively. It shows that LLTSA-AE is an effective dimensionality reduction method.

Abstract Background This study aimed to develop cardiovascular disease (CVD) risk equations for Chinese patients with newly diagnosed type 2 diabetes (T2D) to predict 10-, 20-, and 30-year of risk. Methods Risk equations for forecasting the occurrence of CVD were developed using data from 601 patients with newly diagnosed T2D from the Da Qing IGT and Diabetes Study with a 30-year follow-up. The data were randomly assigned to a training and test data set. In the training data set, Cox proportional hazard regression was used to develop risk equations to predict CVD. Calibration was assessed by the slope and intercept of the line between predicted and observed probabilities of outcomes by quintile of risk, and discrimination was examined using Harrell’s C statistic in the test data set. Using the Sankey flow diagram to describe the change of CVD risk over time. Results Over the 30-year follow-up, corresponding to a 10,395 person-year follow-up time, 355 of 601 (59%) patients developed incident CVD; the incidence of CVD in the participants was 34.2 per 1,000 person-years. Age, sex, smoking status, 2-h plasma glucose level of oral glucose tolerance test, and systolic blood pressure were independent predictors. The C statistics of discrimination for the risk equations were 0.748 (95%CI, 0.710–0.782), 0.696 (95%CI, 0.655–0.704), and 0.687 (95%CI, 0.651–0.694) for 10-, 20-, and 30- year CVDs, respectively. The calibration statistics for the CVD risk equations of slope were 0.88 (P = 0.002), 0.89 (P = 0.027), and 0.94 (P = 0.039) for 10-, 20-, and 30-year CVDs, respectively. Conclusions The risk equations forecast the long-term risk of CVD in patients with newly diagnosed T2D using variables readily available in routine clinical practice. By identifying patients at high risk for long-term CVD, clinicians were able to take the required primary prevention measures.

Nowadays, algorithms are extensively used on social platforms for content recommendations and user connections. In this study, through semi-structured interviews with 22 China-based users of RED (i.e., an algorithm-mediated platform similar to TikTok), we investigate how users who have experienced mental illnesses (depression, anxiety, and bipolar disorder) understand RED algorithms and how these algorithms shape their self-disclosure, imagined audience, and community building. Specifically, both the norms of self-disclosure and content recipients are governed by algorithms, while users with limited agency form various folk theories to navigate the process. Moreover, based on accurate content recommendations, the algorithms of RED enable users who have experienced mental illnesses to connect with similar others across the platform. By proposing the concept of an “algorithmically woven community,” we conceptualize and visualize a novel mechanism of how an algorithm works akin to a responsive authority to weave a loosely knit, decentralized , and boundless network.

ABSTRACT: Newcastle disease virus (NDV) is an RNA virus taking poultry as the host, and the Newcastle disease (ND) caused by NDV is one of the diseases with serious damage to the health of poultry. Mx encoding by myxovirus resistance gene, induced by type I interferon (IFN), has a wide range of antiviral and GTPase activities in human, mice, and other species via inhibition virus replication. However, the antiviral ability of chicken Mx is still a controversial issue. To explore the effect of chicken Mx post-NDV infection, Mx-knockout DF-1 cells were constructed via CRISPR/Cas9 gene editing system. The number of copies of NDV was detected by RT-qPCR, and the mRNA expression levels of IRF-7, IFN-α, IFN-β, TNF-α, p21, p27, and Bak in DF-1 cells were analyzed after NDV infection. Compared with control cells, virus titers were much higher in Mx-knockout DF-1 cells post-NDV infection. The deficiency of Mx aggravated the cell pathological features post-NDV infection, and promoted the expression levels of IRF-7, IFN-α, IFN-β, and pro-inflammatory cytokine TNF-α in host cells. In addition, cells with Mx deficiency could alleviate the harm from virus by enhancing the expression of p21, p27, and Bak, which related to cell proliferation apoptosis. In conclusion, Mx played an important role in antivirus invasion. In the absence of Mx, cells could alleviate the harm from virus infection via retarding cell proliferation and enhancing cell apoptosis.

[Objective] The effects of changes in aboveground litter, underground roots, and mycorrhizal inputs on soil microaggregates of restored red soil forestland were analyzed in order to provide a basis for soil function reconstruction and understanding the ecosystem carbon cycle after forest restoration of degraded lands. [Methods] The study was conducted in a pure Schima superba forest, a typical broad-leaved forest recovered from eroded and degraded red soil in a subtropical region. Five input treatments were established: no litter (CT), mycorrhiza (M), root+mycorrhiza (RM), aboveground+underground litter (LRM), and double aboveground+underground litter (DLRM). The composition of soil microaggregates, organic carbon, and their chemically bound forms were analyzed. [Results] There were no significant differences in soil microaggregate mass percentage, organic carbon, Ca-SOC, Fe (Al)-SOC, and Ca-SOC/SOC among the different treatments (p>0.05). Compared with CT, LRM reduced Fe (Al)-SOC/SOC of microaggregates of size 20—50 μm and 50—200 μm by 40.06% and 46.67%, respectively (p

Abstract Introduction Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that may lead to bone erosion and disability. Although there are many biological therapies in RA treatment nowadays, such as etanercept and tofacitinib, there are still a considerable number of patients who cannot achieve clinical deep remission, which makes patients feel pain and stiffness of joints. As a traditional Chinese medicine preparation, Wangbi granule showed a synergistic role with methotrexate in the treatment of RA patients with “kidney deficiency and dampness” or “stasis blocking channels”. Therefore, it is a promising therapeutic strategy for the clinical deep remission of RA. In this study, Wangbi granule will be used as the test drug. The investigators conduct this study to evaluate the efficacy and safety of Wangbi granule in the treatment of patients who have not achieved deep remission despite the use of methotrexate and tofacitinib. Methods and analysis Two parallel randomized, triple-blind, placebo-controlled trials will be conducted. In six study centers, 340 eligible RA patients will be recruited and randomly allocated to either the intervention group or the control group (in a 1:1 ratio). They will receive Wangbi granule or Wangbi placebo 12.0 g each time, three times a day for 12 weeks. The primary outcome is the disease activity score derivative for 28 joints (DAS28). Secondary outcomes are patient-reported outcomes, American College of Rheumatology 50% response criteria (ACR50), fatigue scale-14 (FS-14), visual analogue scale for pain (VAS), health assessment questionnaire disability index (HAQ-DI) and biomarkers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Expected outcomes The success of this study will provide strong evidence to confirm the efficacy and safety of Wangbi granule in the treatment of RA. Trial registration The trial has been registered in the ClinicalTrials Registry (NCT05540938, Date: 09/15/2022, https://clinicaltrials.gov/ct2/show/NCT05540938 )

Abstract Background To investigate whether the attenuation coefficient (ATT) can be used as a noninvasive index to assess liver involvement in children and adolescents with Wilson’s disease (WD). Methods Children and adolescents diagnosed with WD were retrospectively collected from the First Affiliated Hospital of the Anhui University of Traditional Chinese Medicine between May 2022 and August 2022. The findings on ATT, Shear Wave Measurement (SWM), AST to platelet ratio index (APRI), and fibrosis 4 (FIB-4) score were obtained. The liver involvement of WD was classified into 3 groups based on serum levels of collagen type IV (CIV), hyaluronic acid (HA), laminin (LN) and precollagen type III N-terminal peptide (PIIINP): (1) Group1 (n = 25), no abnormalities in CIV, HA, LN and PIIINP; (2) Group2 (n = 19), elevation of 1 or 2 indexes in CIV, HA, LN, and PIIINP; Group3 (n = 18), elevation of 3 or 4 indicators in CIV, HA, LN, and PIIINP. The levels of ATT, SWM, APRI and FIB-4 were compared between the 3 groups; and correlation of ATT with SWM and triglyceride (TG) was performed using Spearman's correlation analysis. The Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of ATT alone and its combination with SWM, APRI, and FIB-4 in children and adolescents with WD. Results A total of 62 children and adolescents with WD were retrospectively retrieved. ATT levels were significantly different in intergroup comparisons (P

Human cancers typically express a high level of tumor-promoting mutant p53 protein (Mutp53) with a minimal level of tumor-suppressing wild-type p53 protein (WTp53). In this regard, inducing Mutp53 degradation while activating WTp53 is a viable strategy for precise anti-tumor therapy. Herein, a new carrier-free nanoprodrug (i.e., Mn-ZnO2 nanoparticles) was developed for concurrent delivery of dual Zn-Mn ions and reactive oxygen species (ROS) within tumor to regulate the p53 protein for high anti-tumor efficacy. In response to the mild tumor acidic environment, the released Zn2+ and H2O2 from Mn-ZnO2 NPs induced ubiquitination-mediated proteasomal degradation of Mutp53, while the liberative Mn2+ and increased ROS level activated the ATM-p53-Bax pathway to elevate WTp53 level. Both in vitro and in vivo results demonstrated that pH-responsive decomposition of Mn-ZnO2 NPs could effectively elevate the intracellular dual Zn-Mn ions and ROS level and subsequently generate the cytotoxic hydroxyl radical (•OH) through the Fenton-like reaction. With the integration of multiple functions (i.e., carrier-free ion and ROS delivery, tumor accumulation, p53 protein modulation, toxic •OH generation, and pH-activated MRI contrast) in a single nanosystem, Mn-ZnO2 NPs demonstrate its superiority as a promising nanotherapeutics for p53-mutated tumor therapy.

With the progress of urbanization and the refining of research content, it is more urgent to study the integration of urban and rural public services. In this paper, with the papers on the main journals containing urban and rural public service integration research results as research object, bibliometric method and the visualization method of CiteSpace and CNKI were adopted to carry out fundamental reviewing from the number of papers, authors and institutions, and knowledge background, and then to conduct comprehensive analysis on hot research topics, theme connotation, and the law of development, and finally to get the objective results from the view of result evaluation and research extension, so as to provide the necessary basis and enlightenment for further study of urban and rural public service integration in China in the future.

Principal component analysis network (PCANet) is a feature learning algorithm that is widely used in face recognition and object classification. However, original PCANet still has some shortages. One is that the principal component analysis (PCA) algorithm only extracts features by considering the global structure. The other lies in that the original PCANet only employs one particular single layer convolutional results, which loses the information of other convolutional layers. In this paper, we propose a new simple and efficient convolutional neural network called global and local structure network (GLSNet) to address the problems. The network extracts the features both from the global structure and the local structure of the original data space. Specifically, a principal component analysis (PCA) convolutional layer which learns the filters by PCA algorithm is used to remove the noises and redundant information at the first stage. Then at the second stage, another PCA convolution is added to extract features by considering the global structure. As for the local structure, we use the neighborhood preserving embedding (NPE) algorithm to learn the convolutional filters. At the output stage, the global structure feature extracted by PCA convolution and the local structure feature extracted by NPE convolution is concatenated as a united feature. Furthermore, the first layer convolutional feature is also taken into consideration to obtain shallow-level information. Finally, these features are concatenated as a united feature, and a spatial pyramid pooling layer is followed to pool above the united features. To test the effectiveness of the proposed algorithm, the experiments on some image datasets, including three types: human face dataset, object dataset, and handprinted dataset, proceeded. And it performs better than the original PCANet and some improvement algorithms of PCANet, such as PLDANet, and MMPCANet.

Abstract Objective To investigate the correlation between the triglyceride-glucose (TyG) index and rheumatoid factor levels and the existence of cardiovascular disease in patients in the rheumatoid arthritis population and to analyze their potential value in predicting the risk of cardiovascular disease. Methods Patients with rheumatoid arthritis treated by the Traditional Chinese Medicine Department of Rheumatism of the China-Japan Friendship Hospital from 2019–01 to 2021–12 were included in this retrospective study. Regression analysis was performed with multifactor-corrected multimodal logistic models to observe the correlation between the TyG index and rheumatoid factor and cardiovascular disease risk, construct predictive models and assess the potential predictive value of the variables on cardiovascular disease risk with receiver operating characteristic curves. The results were further corrected by sensitivity analysis and trend tests. Results A total of 418 patients with rheumatoid arthritis were included in the study. In the rheumatoid arthritis population, high rheumatoid factor (OR = 1.002, 95% CI = 1.001–1.002, P

Fibroblast-activated protein-α (FAP) is a type II integrated serine protease expressed by activated fibroblasts during fibrosis or inflammation. Fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) synovial sites abundantly and stably overexpress FAP and play important roles in regulating the cellular immune, inflammatory, invasion, migration, proliferation, and angiogenesis responses in the synovial region. Overexpression of FAP is regulated by the initial inflammatory microenvironment of the disease and epigenetic signaling, which promotes RA development by regulating FLSs or affecting the signaling cross-linking FLSs with other cells at the local synovium and inflammatory stimulation. At present, several treatment options targeting FAP are in the process of development. This review discusses the basic features of FAP expressed on the surface of FLSs and its role in RA pathophysiology and advances in targeted therapies.

Abstract Infection with influenza A virus (IAV) can trigger pulmonary inflammation and lung damage. Osteopontin (OPN) is an essential regulator of cell death and immunity. However, the role and underlying mechanism of OPN in cell death in IAV-induced pulmonary injury remain poorly understood. Here, we demonstrated that OPN-deficient (OPN−/−) mice were insensitive to IAV, exhibiting decreased viral loads and attenuated lung injury after IAV infection compared to those in wild-type (WT) mice. Moreover, macrophage necroptosis was significantly reduced in OPN−/− mice infected with IAV compared to that in infected WT mice. OPN increased the expression of necroptosis-related genes and exacerbated macrophage necroptosis in IAV-infected THP1 cells. Notably, adoptive transfer of WT bone marrow-derived macrophages (BMDMs) or OPN−/− BMDMs into mice restored resistance to influenza infection, and the rescue effect of OPN−/− BMDMs was better than that of WT BMDMs. Collectively, these results suggest that OPN deficiency in macrophages reduces necroptosis, which leads to a decrease in viral titers and protects against IAV infection. Therefore, OPN is a potential target for the treatment of IAV infection.

The EPIDERMAL PATTERNING FACTOR (EPF) plays a crucial role in plant response to abiotic stress. While the EPF has been extensively studied in model plants such as Arabidopsis thaliana, there is a lack of research on identifying EPF genes in the whole sorghum genome and its response to drought stress. In this study, we employed bioinformatics tools to identify 12 EPF members in sorghum. Phylogenetic tree analysis revealed that SbEPFs can be categorized into four branches. Further examination of the gene structure and protein conservation motifs of EPF family members demonstrated the high conservation of the SbEPF sequence. The promoter region of SbEPFs was found to encompass cis-elements responsive to stress and plant hormones. Moreover, real-time fluorescence quantitative results indicated that the SbEPFs have a tissue-specific expression. Under drought stress treatment, most SbEPF members were significantly up-regulated, indicating their potential role in drought response. Our research findings establish a foundation for investigating the function of SbEPFs and offer candidate genes for stress-resistant breeding and enhanced production in sorghum.

Abstract Background Soil acidification caused by acid rain (AR) can damage plant roots, which in turn negatively impacts plant health. In response to changing AR types, research efforts to elucidate their specific impacts on plants have become intense. Methods For this study, we investigated the effects of simulated sulfuric, nitric, and mixed AR on the root systems of Quercus acutissima Carr. and Cunninghamia lanceolata (Lamb.) Hook. under different acidity levels. Results As the AR S/N ratio and pH decreased, the height growth rate (HGR), basal diameter growth rate (DGR), total root length (TRL) and total root surface area (TRS) of C. lanceolata decreased, whereas the TRL and TRS of Q. acutissima remained the same. When the NO3 − concentration in AR was increased, the root activity, superoxide dismutase (SOD) and catalase (CAT) activities of C. lanceolata roots revealed a downward trend; however, the root activity of Q. acutissima and the peroxidase (POD) activity of C. lanceolata roots revealed an upward trend. Further, redundant analysis and structural equation models indicated that AR pH had a greater impact on the HGR of Q. acutissima than that of C. lanceolata, while the impact of the AR S/N ratio on C. lanceolata growth rates was greater than that of Q. acutissima. Conclusions Our results suggested that the root systems of different tree species had variable responses to AR, and the AR S/N ratio was an important factor affecting plant root growth. This might facilitate new strategies for the cultivation and protection of plantations in the future.

Abstract Aim This study aimed to assess whether a higher insulin response increased the long-term risk of mortality in a non-diabetic population. Methods A total of 446 people with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) who participated in the Da Qing Diabetes Study, were stratified into quartiles subgroups according to their baseline insulin area under the curve (AUC) during oral glucose tolerance test, defined as Q1, Q2, Q3 and Q4. The participants were followed from 1986 to 2016 to assess the risk of death in association with the magnitude of post-load insulin response. Results Over 30 years, the rates of all cause death were 9.94, 14.81, 15.02, and 17.58 per 1000 person-years across the four groups respectively. The rate for cardiovascular disease (CVD) death was 5.14, 6.50, 6.80 and 10.47 per 1000 person-years. Compared with Q1, the risk of all-cause death was significantly higher in participants in Q4 (HR = 2.14, 95% CI 1.34–3.42), Q3 (HR = 1.94, 95% CI 1.20–3.14), and Q2 group (HR = 1.70, 95% CI 1.06–2.74). In the Fine-Gray model with non-CVD death as competing risk, the increased insulin AUC were also significantly associated with the CVD death (Q4 vs Q1, HR = 2.04, 95% CI 1.10–3.79). In the fractional polynomial regression analysis, a nonlinear association between insulin AUC and all-cause and CVD death was demonstrated. In addition, insulin AUC was associated with a progressively higher risk of all-cause death and CVD death (fractional power 3, P

Cadmium (Cd) pollution is a serious threat to plant growth and human health. Although the mechanisms controlling the Cd response have been elucidated in other species, they remain unknown in Sorghum (Sorghum bicolor (L.) Moench), an important C4 cereal crop. Here, one-week-old sorghum seedlings were exposed to different concentrations (0, 10, 20, 50, 100, and 150 μM) of CdCl2 and the effects of these different concentrations on morphological responses were evaluated. Cd stress significantly decreased the activities of the enzymes peroxidase (POD), superoxide dismutase (SOD), glutathione S-transferase (GST) and catalase (CAT), and increased malondialdehyde (MDA) levels, leading to inhibition of plant height, decreases in lateral root density and plant biomass production. Based on these results, 10 μM Cd concentration was chosen for further transcription and metabolic analyses. A total of 2683 genes and 160 metabolites were found to have significant differential abundances between the control and Cd-treated groups. Multi-omics integrative analysis revealed that the flavonoid biosynthesis pathway plays a critical role in regulating Cd stress responses in sorghum. These results provide new insights into the mechanism underlying the response of sorghum to Cd.

Cefoperazone/sulbactam-induced hypoprothrombinaemia is associated with longer hospital stays and increased risk of death. The aim of this study was to develop and validate a nomogram for predicting the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia in hospitalized adult patients. This retrospective cohort study involved hospitalized adult patients at Xi'an Central Hospital from January 2020 to December 2022 based on the Chinese pharmacovigilance system developed and established by the Adverse Drug Reaction Monitoring Center in China. Independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were obtained using multivariate logistic regression and were used to develop and establish the nomogram. According to the same standard, the clinical data of hospitalized patients using cefoperazone/sulbactam at the Third Affiliated Hospital of Xi'an Medical University from January 1, 2023 to June 30, 2023 were collected as the external validation group. The 893 hospitalized patients included 95 who were diagnosed with cefoperazone/sulbactam-induced hypoprothrombinaemia. Our study enrolled 610 patients: 427 in the training group and 183 in the internal validation group. The independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were surgery (odds ratio [OR] = 5.279, 95% confidence interval [CI] = 2.597-10.729), baseline platelet count ≤50×109/L (OR = 2.492, 95% CI = 1.110-5.593), baseline hepatic dysfunction (OR = 12.362, 95% CI = 3.277-46.635), cumulative defined daily doses (OR = 1.162, 95% CI = 1.162-1.221) and nutritional risk (OR = 16.973, 95% CI = 7.339-39.254). The areas under the curve (AUC) of the receiver operating characteristic for the training and internal validation groups were 0.909 (95% CI = 0.875-0.943) and 0.888 (95% CI = 0.832-0.944), respectively. The Hosmer-Lemeshow tests yielded p = 0.475 and p = 0.742 for the training and internal validation groups, respectively, confirming the goodness of fit of the nomogram model. In the external validation group (n = 221), the nomogram was equally robust in cefoperazone/sulbactam-induced hypoprothrombinaemia (AUC = 0.837, 95%CI = 0.736-0.938). The nomogram model constructed in this study had good predictive performance and extrapolation, which can help clinicians to identify patients at high risk of cefoperazone/sulbactam-induced hypoprothrombinaemia early. This will be useful in preventing the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia and allowing timely intervention measures to be performed.

Ultrasound is effective to fabricate nanocomplex. Soymilk is a natural nanocarrier with good compatibility. However, information about soymilk-nutraceuticals nanocomplex is limited. In this work, soymilk was used to encapsulate icariin, a well known nutraceutical with poor bioavailability. The effect of ultrasound on the quality of icariin-soymilk nanocomplexes (ISNCs) was investigated. Ultrasound could reduce the particle size, improve the surface hydrophobicity and change the microstructure of soymilk. With increasing ultrasound treatment time, an increased surface hydrophobicity was observed. The highest encapsulation efficiency (89.67 %) and loading capacity (28.92 µg/mg) were found for USI-20, whereas the smallest particle size (132.47 nm) was observed for USI-120. USI-60 showed the lowest ζ-potential (-31.33 mV) and the highest bioaccessibility (76.08 %). Ultrasound could enhance the storage stability of ISNCs. The data of NMR and fluorescence indicated that ISNCs were mainly stabilized by hydrophobic interaction.

In order to improve the quality of outlet temperature of DSG trough solar collector, the classical multi-objective optimization method is used to optimize the parameters of PID controller. In the optimization process, two kinds of objective functions are designed, one kind is the direct objective functions, the other kind is the indirect functions. The simulation curves of the parameters obtained by the multi-objective optimization method are much better than those of the original literature in the adjustment time and other indicators. In addition, the control valve position changes are within the allowable range, and the control system also has a certain robustness. Finally, the solution time of indirect objective function is about 1/6 of that of direct objective function, and there is no need to determine the ideal value of control index. Therefore, it is reasonable and effective to use multi-objective optimization algorithm and indirect objective function to optimize the parameters of PID controller for the outlet temperature of trough solar collector.

This study aimed to explore the influence of material design parameters on the physical and mechanical properties of recycled asphalt. A Box–Behnken design was employed to determine the optimal preparation scheme for 17 groups of recycled asphalt. The effects of styreneic methyl copolymer (SMC) regenerant content, styrene–butadiene–styrene (SBS)-modified asphalt content, and shear temperature on the mechanical properties of recycled asphalt were analyzed using conventional and high/low-temperature rheological tests. The optimal processing parameters were determined by a response surface model based on multiple response indexes. The results revealed that the SBS-modified asphalt content had the most significant effect on the penetration of recycled asphalt. An increase in SMC regenerant content led to a gradual decrease in the rutting factor, while SBS-modified asphalt content had the opposite effect. The usage of SMC regenerant helped to reduce non-recoverable creep compliance by adjusting the proportion of viscoelastic–plastic components in recycled asphalt. Furthermore, the stiffness modulus results indicated that the addition of SMC regenerant improved the recovery performance of recycled asphalt at a low temperature. The recommended contents of SMC regenerant and SBS-modified asphalt are 7.88% and 150%, respectively, with a shear temperature of 157.7 °C.

Five hundred and fifty traditional villages in Shanxi Province were studied with ArcGIS 10.2 tools, using the combination of quantitative and qualitative methods such as average nearest neighbor index, kernel density estimation, and buffer analysis. The spatial distribution characteristics and settlement characteristics of traditional villages in Shanxi Province were studied from the perspective of watershed. The results show that: The spatial distribution types of ancient villages in Shanxi Province in the four major basins of Fen, Hutuo, Qin, and Zhangwei rivers are all condensed. The traditional villages in the province present a distribution pattern of “three groups and more scattered points in one area”, more than half of the ancient villages are located in the Yellow River system. Traditional villages in Shanxi Province have similarities in near-water distribution, as well as differences in distribution between upper, middle, and lower reaches, main and tributaries, and left and right banks. The settlement characteristics in different basins are remarkable. The Yellow River Basin is represented by cave dwellings, the Fen River Basin is represented by Shanxi Merchants’ Courtyard, and the Qin River Basin is represented by castle-like settlements.

Objective: Losartan and activation of the peroxisome proliferator-activated receptor-γ (PPARγ) have been previously reported to alleviate the progression of osteoarthritis (OA). However, the nature of the interaction between losartan and PPARγ in OA remains elusive. Therefore, we aimed to investigate the mechanism of the regulation of PPARγ by losartan in the context of OA. Methods: Clinical samples of OA patients were collected and the chondrocytes were further isolated, and used to construct OA chondrocyte model via induction with IL-1β. An OA mouse model was developed by the surgical destabilization of the medial meniscus (DMM). OA chondrocytes were treated with losartan, PPARγ siRNA and the PPAR-γ agonist GW1929 alone or in combination. Furthermore, the OA mice were treated with varying doses of losartan to determine the best mode of administration and treatment dose. Subsequently, the DMM mice were treated with losartan and GW9662. Expression of PPARγ, key proteins of the transforming growth factor-beta1 (TGF-β1) signaling pathway and the markers of OA degeneration were evaluated by the Western blot analysis, while effects on OA inflammatory factors were determined by ELISA. Results: The downregulation of PPARγ and the upregulation of TGF-β1 signaling pathway were detected in the OA cartilage tissues and chondrocytes. Losartan treatment or PPARγ activation contributes to reduced levels of IL-6, IL-1β, TNF-α, and COX-2, expression of TGF-β1, MMP-13, ADAMTS-4, ADAMTS-5, HtrA1, and iNOS, along with reduced Smad2 and Smad3 phosphorylation, but elevated PPARγ and Collagen II expression in vivo and in vitro. Additionally, the intraarticular injection of losartan into the knee joint proved to be the best mode of administration, and 10 ​mg/mL being the optimal treatment concentration. Conclusion: Our results show that losartan could arrest the progression of OA by upregulating PPARγ expression and inactivating the TGF-β1 signaling pathway.The translational potential of this article: Our results provide a biological rationale for the use of losartan as a potential candidate for OA treatment.

Leaf rolling is an important agronomic trait in wheat (Triticum aestivum L.). Moderate leaf rolling keeps leaves upright and maintains the relatively normal photosynthesis of plants under drought stress. However, the molecular mechanism of wheat leaf rolling remains unclear. Here, we identified a candidate gene TaMYB5-3A that regulates leaf rolling by using a genome-wide association study (GWAS) in a panel of 323 wheat accessions. Phenotype analysis indicated that the leaves of tamyb5 mutants were flatter than that of the wild type under drought condition. A nucleotide variation in the TaMYB5-3A coding region resulted in a substitution of Thr to Lys, which corresponds to two alleles SNP-3A-1 and SNP-3A-2. The leaf rolling index (LRI) of the SNP-3A-1 genotype was significantly lower than that of the SNP-3A-2 genotype. In addition, TaMYB5-3A alleles were associated with canopy temperature (CT) in multiple environments. The CT of the SNP-3A-1 genotype was lower than that of the SNP-3A-2 genotype. Gene expression analysis showed that TaMYB5-3A was mainly expressed in leaves and down-regulated by PEG and ABA treatment. TaMYB5 induces TaNRL1 gene expression through the direct binding to the AC cis-acting element of the promoter of the target gene, which was validated by EMSA (electrophoretic mobility shift assay). Our results revealed a crucial molecular mechanism in wheat leaf rolling and provided the theoretical basis and a gene resource for crop breeding.

Abstract Background Lecanemab (BAN2401), an IgG1 monoclonal antibody, preferentially targets soluble aggregated amyloid beta (Aβ), with activity across oligomers, protofibrils, and insoluble fibrils. BAN2401-G000-201, a randomized double-blind clinical trial, utilized a Bayesian design with response-adaptive randomization to assess 3 doses across 2 regimens of lecanemab versus placebo in early Alzheimer’s disease, mild cognitive impairment due to Alzheimer’s disease (AD) and mild AD dementia. Methods BAN2401-G000-201 aimed to establish the effective dose 90% (ED90), defined as the simplest dose that achieves ≥90% of the maximum treatment effect. The primary endpoint was Bayesian analysis of 12-month clinical change on the Alzheimer’s Disease Composite Score (ADCOMS) for the ED90 dose, which required an 80% probability of ≥25% clinical reduction in decline versus placebo. Key secondary endpoints included 18-month Bayesian and frequentist analyses of brain amyloid reduction using positron emission tomography; clinical decline on ADCOMS, Clinical Dementia Rating-Sum-of-Boxes (CDR-SB), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14); changes in CSF core biomarkers; and total hippocampal volume (HV) using volumetric magnetic resonance imaging. Results A total of 854 randomized subjects were treated (lecanemab, 609; placebo, 245). At 12 months, the 10-mg/kg biweekly ED90 dose showed a 64% probability to be better than placebo by 25% on ADCOMS, which missed the 80% threshold for the primary outcome. At 18 months, 10-mg/kg biweekly lecanemab reduced brain amyloid (−0.306 SUVr units) while showing a drug-placebo difference in favor of active treatment by 27% and 30% on ADCOMS, 56% and 47% on ADAS-Cog14, and 33% and 26% on CDR-SB versus placebo according to Bayesian and frequentist analyses, respectively. CSF biomarkers were supportive of a treatment effect. Lecanemab was well-tolerated with 9.9% incidence of amyloid-related imaging abnormalities-edema/effusion at 10 mg/kg biweekly. Conclusions BAN2401-G000-201 did not meet the 12-month primary endpoint. However, prespecified 18-month Bayesian and frequentist analyses demonstrated reduction in brain amyloid accompanied by a consistent reduction of clinical decline across several clinical and biomarker endpoints. A phase 3 study (Clarity AD) in early Alzheimer’s disease is underway. Trial registration Clinical Trials.gov NCT01767311 .

Biomass fuels play an important role in the field of fluidized bed combustion, but due to the diversity and uncertainty of fuels, there are usually some problems of high CO emission that cannot be directly solved by combustion adjustment. In this paper, a 75 t/h biomass fluidized bed was taken as the research object. It was observed from the field test that the gas incomplete combustion loss reached 12.13% when mono-combustion of wheat straw was conducted, and the CO concentration in the exhaust gas exceeded 30k ppm. Combined with the CPFD numerical simulation, the combustion characteristics and influence of secondary air layout on CO reduction performance were discussed in detail. The results revealed that the gas temperature gradually increased along furnace height under the initial condition, and the maximum temperature was more than 1000 °C at furnace outlet. The air curtain of the secondary air jets was insufficient, and the wheat straw rose rapidly as it entered into the furnace. By arranging adjacent secondary air ports above each fuel-feeding inlet, the residence time of particles in the furnace could be significantly increased, thus, the furnace temperature distribution was more reasonable and the CO emission was reduced by 58.6%.

Fatigue cracking is a common form of flexible pavement distress, which generally starts and spreads through bitumen. To address this issue, self-healing elastomer (SHE) modified bitumens were elaborated to assess whether these novel materials can overcome the neat asphalt (NA) fatigue performance and whether the current failure definition, failure criterion, and fatigue-restoration criteria can fit their performance. All bitumens were subjected to short-term and long-term aging. Linear amplitude sweep (LAS) test, LAS with rest period (LASH), and simplified viscoelastic-continuum-damage (S-VECD) model were utilized to appraise the behavior of the mentioned bitumens. The results showed that maximum stored pseudo-strain energy (PSE) and tau (τ) × N (number of loading cycles) failure definitions exhibited high efficiency to accommodate the fatigue life of NA and SHE-modified bitumens. Both failure criteria identified that SHE-modified bitumen (containing 1% of SHE) showed the highest increment of fatigue performance (67.1%) concerning NA. The failure criterion based on total released PSE, in terms of the area under the released PSE curve, was the only failure concept with high efficiency (R2 up to 0.999) to predict asphalt binder fatigue life. As well, the current framework to evaluate bitumen self-restoration failed to fully accommodate asphalt binder behavior, because bitumen with higher restoration could not exhibit greater fatigue performance. Consequently, a new procedure to assess this property including fatigue behavior was proposed, showing consistent results, and confirming that SHE-modified bitumen (containing 1% of SHE) exhibited the highest increment of fatigue performance (154.02%) after application of the rest period. Hence, the optimum SHE content in NA was 1%. Furthermore, it was found that a greater number of loading cycles to failure (Nf) did not ensure better fatigue performance and stored PSE influenced the bitumen fatigue behavior.

Evaluating sea-level projections used by the IPCC is challenging due to the short overlap with measurements. Here, the authors show that observed global and regional sea-level trends confirm projections and that the acceleration of sea-level rise is between the one expected from the scenarios RCP4.5 and RCP8.5.

For the problem of multiple sensor faults in the automated guided forklift (AGF), an equivalent model with system faults and disturbances is established. To detect multiple sensor faults in the AGF, a sliding mode observer (SMO) is proposed. It introduces a fault estimation algorithm that is designed by the fault residual and the residual is only sensitive to sensor faults which means that the SMO is robust to unknown input disturbances. On the other side, it can also judge the faulty sensor according to the feature vector of different sensors. To judge the type of sensor faults accurately, a mathematical model of sensor fault characteristics is established and it can provide a foundation for choosing appropriate fault-tolerant output compensation measures. Then an active fault-tolerant control method based on state feedback is proposed. It can restore the control system to normal and maintain the stability of the control system. Finally, experiments are given to verify the effectiveness of the proposed fault-tolerant control strategy.

Introduction Ankle pump exercise (APE) is an effective method to prevent deep vein thrombosis (DVT) in the lower extremities. However, traditional APE at a frequency of 3 times/min applied in the clinic lacked high compliance, and individuals were found to prefer an APE of 30 times/min. This study aimed to compare the effects of APEs with the above two different frequencies on the venous hemodynamics and fatigue of lower extremities. Methods The study applied a randomized cross-over design, and 307 healthy adults were randomly assigned into two groups, whose left feet performed 5 minutes of traditional APE (3 times/min, after 10 minutes of rest) and 5 minutes of selected APE (30 times/min, after 10 minutes of rest) in different orders. The diameters and blood flow velocities of the external iliac vein, femoral vein, and popliteal vein of the left extremities were recorded with the color doppler ultrasound when participants were at rest and after 5 minutes of traditional or selected APE. The fatigue of lower extremities was assessed with the Rating of Perceived Exertion (RPE) after the participants performed 5 minutes of different APEs. Results After both traditional APE and selected APE, the diameters and blood flow (peak systolic) velocities of the external iliac vein, femoral vein, and popliteal vein increased significantly in the participants (P.05). However, participants reported that traditional APE caused higher fatigue, and 252 (82.1%) participants preferred APE at 30 times/min. Conclusion Both traditional and selected APE could increase venous blood flow in the lower extremity. Despite the equivalent effects, the selected APE of 30 times/min may cause less fatigue than the traditional one of 3 times/min.

ObjectiveThe clinical features of interstitial lung disease (ILD) in patients with dermatomyositis (DM) and negative myositis autoantibodies had not been exactly demonstrated previously. This study aimed to describe and expand the phenotype of interstitial lung disease (ILD) in this cohort of patients.MethodsA total of 1125 consecutive Chinese patients with idiopathic inflammatory myopathies (IIM) between 2006 and 2020 were screened retrospectively. All proven cases of isolated ILD with both negative myositis-specific autoantibodies (MSA) and negative myositis-associated autoantibodies (MAA) were selected for inclusion. The clinical features and outcome among this group, MDA5+DM (DM patients with positive anti-MDA5 antibody) and ASS (patients with positive anti-aminoacyl tRNA synthetases antibodies were recorded and compared.ResultsOf 1125 IIM patients with an average follow-up of 6 years, 154 DM patients with negative MSA and MAA (MSA/MAA) were identified, with an ILD incidence of 46.8%. DM-ILD Patients with negative MSA/MAA presented younger age at onset (p

The Chinese chestnut (Castanea mollissima Bl.) is a woody nut crop with a high ecological value. Although many cultivars have been selected from natural seedlings, elite lines with comprehensive agronomic traits and characters remain rare. To explore genetic resources with aid of whole genome sequence will play important roles in modern breeding programs for chestnut. In this study, we generated a high-quality C. mollissima genome assembly by combining 90× Pacific Biosciences long read and 170× high-throughput chromosome conformation capture data. The assembly was 688.93 Mb in total, with a contig N50 of 2.83 Mb. Most of the assembled sequences (99.75%) were anchored onto 12 chromosomes, and 97.07% of the assemblies were accurately anchored and oriented. A total of 33,638 protein-coding genes were predicted in the C. mollissima genome. Comparative genomic and transcriptomic analyses provided insights into the genes expressed in specific tissues, as well as those associated with burr development in the Chinese chestnut. This highly contiguous assembly of the C. mollissima genome provides a valuable resource for studies aiming at identifying and characterizing agronomical-important traits, and will aid the design of breeding strategies to develop more focused, faster, and predictable improvement programs.

In this work, green fluorescent carbon dots with a high relative quantum yield of 74.13% were synthesized by using one-pot hydrothermal hydrolysis of m-phenylenediamine (mPD) and PEG 1500 in H2SO4 solution at 180 °C for 10 h (mPD-CDs). In the presence of mPD-CDs, Fe2+ can form a complex with 1,10-phenanthroline (Fe(II) – phenanthroline) without interference from mPD-CDs, which has an absorption peak centered at 512 nm and its absorbance is sensitive to the concentration of Fe(II) – phenanthroline. Accordingly, a colorimetric method for the detection of Fe2+ was constructed with a limit of detection (LOD) of 2.98 μM. Moreover, the absorption spectrum of the Fe (II)-phenanthroline complex is overlapping with the excitation and emission spectra of mPD-CDs located at 440 and 516 nm, respectively, resulting in an inner filter effect (IFE) which is sensitive to the concentration of Fe(II) – phenanthroline. Correspondingly, a fluorimetric method for the detection of Fe2+ based on the mPD-CDs/phenanthroline system was built with a LOD as low as 0.59 μM. Therefore, colorimetric and fluorimetric dual mode detection of Fe2+ in aqueous solution can be achieved by a carbon dots/phenanthroline system. Keywords: Carbon dots, IFE, Colorimetry, Fluorimetry, Fe2+