Search

Abstract Complicated associations between multiplexed environmental factors and aging are poorly understood. We manipulated aging using multidimensional metrics such as phenotypic age, brain age, and brain volumes in the UK Biobank. Weighted quantile sum regression was used to examine the relative individual contributions of multiplexed environmental factors to aging, and self-organizing maps (SOMs) were used to examine joint effects. Air pollution presented a relatively large contribution in most cases. We also found fair heterogeneities in which the same environmental factor contributed inconsistently to different aging metrics. Particulate matter contributed the most to variance in aging, while noise and green space showed considerable contribution to brain volumes. SOM identified five subpopulations with distinct environmental exposure patterns and the air pollution subpopulation had the worst aging status. This study reveals the heterogeneous associations of multiplexed environmental factors with multidimensional aging metrics and serves as a proof of concept when analyzing multifactors and multiple outcomes.

Objective: To develop machine learning-based prediction models for all-cause and premature mortality among the middle-aged and elderly population in China. Method: Adults aged 45 years or older at baseline of 2011 from the China Health and Retirement Longitudinal Study (CHARLS) were included. The stacked ensemble model was built utilizing five selected machine learning algorithms. These models underwent training and testing using the CHARLS 2011–2015 cohort (derivation cohort) and subsequently underwent external validation using the CHARLS 2015–2018 cohort (validation cohort). SHapley Additive exPlanations (SHAP) was introduced to quantify the importance of risk factors and explain machine learning algorithms. Result: In derivation cohort, a total of 10,677 subjects were included, 478 died during the follow-up. The stacked ensemble model demonstrated the highest efficacy in terms of its discrimination capability for predicting all-cause mortality and premature death, with an AUC[95 % CI] of 0.826[0.792–0.859] and 0.773[0.725–0.821], respectively. In validation cohort, the corresponding AUC[95 % CI] were 0.803[0.743–0.864] and 0.791[0.719–0.863], respectively. Risk factors including age, sex, self-reported health, activities of daily living, cognitive function, ever smoker, levels of systolic blood pressure, Cystatin C and low density lipoprotein were strong predictors for both all-cause mortality and premature death. Conclusion: Stacked ensemble models performed well in predicting all-cause and premature death in this Chinese cohort. Interpretable techniques can aid in identifying significant risk factors and non-linear relationships between predictors and mortality.

Abstract Background The meticulous selection of appropriate vaccine adjuvants is crucial for optimizing immune responses. Traditionally, pemphigus vulgaris (PV), an autoimmune disorder, has been modelled using complete Freund's adjuvant (CFA). In this study, we aimed to discern potential variations in immune responses elicited by Toll‐like receptor (TLR) ligands as compared to CFA. Methods A comprehensive investigation was conducted, comparing the effects of these adjuvants in conjunction with ovalbumin or desmoglein‐3. Flow cytometry was employed to analyse distinct cell subsets, while enzyme‐linked immunosorbent assay quantified antigen‐specific antibodies and cytokine levels. Histological examination of harvested skin tissues and transcriptome analysis of skin lesions were performed to identify differentially expressed genes. Results TLR ligands demonstrated efficacy in inducing PV‐like symptoms in wild‐type mice, in contrast to CFA. This underscored the substantial impact of the adjuvant on self‐antigen tolerance. Furthermore, we proposed an enhanced method for establishing a PV model through adoptive transfer, substituting CFA with TLR ligands. Our results revealed that in contrast to the perception that CFA being the most potent immunopotentiator reported, CFA promoted regulatory T cells (Treg), follicular regulatory T cells and IL‐10‐producing neutrophils, whereas TLR ligands downregulated CCL17 and IL‐10. This suggested potential implications for the recruitment and activation of Treg subsets. While B cell and CD8+ T cell responses exhibited similarity, CFA induced less activation in dendritic cell subsets. A novel mouse model of PV and systemic comparison of immunostimulatory effects of adjuvants were provided by this study. Conclusions The systematic comparison of CFA and TLR ligands shed light on the distinctive properties of these adjuvants, presenting innovative mouse models for the investigation of pemphigus. This study significantly contributes to adjuvant research and advances our understanding of PV pathogenesis. Key points/highlights Immunization with desmoglein 3 and Toll‐like receptor (TLR) ligands effectively induces pemphigus symptoms in wild‐type mice, whereas complete Freund's adjuvant (CFA) fails. TLR ligands heightened the autoreactivity of donor cells in the adoptive transfer pemphigus model. CFA promoted regulatory T cells and IL‐10‐producing neutrophils, whereas TLR ligands downregulated CCL17 and IL‐10, leading to more effective immune responses.

Abstract The blood urea nitrogen to albumin ratio (BAR) has been demonstrated as a prognostic factor in sepsis and respiratory diseases, yet its role in severe coronary heart disease (CHD) remains unexplored. This retrospective study, utilizing data from the Medical Information Mart for Intensive Care-IV database, included 4254 CHD patients, predominantly male (63.54%), with a median age of 74 years (IQR 64–83). Primary outcomes included in-hospital, 28-day and 1-year all-cause mortality after ICU admission. The Kaplan–Meier curves, Cox regression analysis, multivariable restricted cubic spline regression were employed to assess association between BAR index and mortality. In-hospital, within 28-day and 1-year mortality rates were 16.93%, 20.76% and 38.11%, respectively. Multivariable Cox proportional hazards analysis revealed associations between the increased BAR index and higher in-hospital mortality (HR 1.11, 95% CI 1.02–1.21), 28-day mortality (HR 1.17, 95% CI 1.08–1.27) and 1-year mortality (HR 1.23, 95% CI 1.16–1.31). Non-linear relationships were observed for 28-day and 1-year mortality with increasing BAR index (both P for non-linearity

The rail transit system plays a crucial role in modern transportation. With the increasing demand for clean and green energy in the transport sector, its energy system is expected to achieve low-carbon and highly efficient energy utilization in rail transit. However, the gradual development of the rail transport energy system has led to an increase in its complexity, and the rising difficulty of system assessment has faced the limitations of traditional assessment methods. Hence, it is essential to develop effective assessment methods. This paper begins by providing a systematic review of the development status of Reliability, Availability, Maintainability and Safety (RAMS) assessment and analyzing the shortcomings of traditional RAMS assessment technology in the context of rail transit energy systems. Subsequently, based on the four fundamental properties of RAMS, it summarizes the current state of key assessment technologies in the field of rail transit. Moreover, the paper delves into the challenges and potential solutions concerning the implementation of RAMS assessment technology for rail transit energy systems. Finally, the paper offers an outlook on the future development of RAMS assessment for rail transport energy systems. By comprehensively analyzing these aspects, the paper aims to contribute valuable insights into optimizing the rail transit energy system, promoting its sustainable and efficient operation in the context of clean and green energy utilization.

Tea grade evaluation is a systematic work with complex and subjective. Grade information from its relevant quality data extracted enables to establish rapid identification method, later of which has guiding meaning to tea production. To establish a rapid identification method of white tea grades, 200 white tea (Bai Mudan) samples with 4 grades were selected as the research objects in this paper, near infrared spectroscopy and gas chromatography-ion mobility spectrometry were used to collect original data. The data dimensions were reduced by principal component analysis or linear discriminant analysis, combed with 7 data mining classifier algorithms to rapidly evaluate the grades of white tea. Results showed that linear discriminant analysis was suitable for dimensionality reduction of the original data from near infrared spectra and gas chromatography-ion mobility spectrometry. After dimensionality reduction of the original data using linear discriminant analysis, classification algorithm including adaptive boosting (Adaboost), k-nearest neighbor (KNN) and multi-layer perceptron (MLP), and random forests (RF), stochastic gradient descent (SGD) and support vector machines (SVM) were used for establishment of white tea grade discriminant models based on near infrared spectroscopy, the correct rate of these models were greater than 94%, and the AUC of the model evaluation index was≥0.95. The discriminant rates of MLP, SGD and SVM models based on gas chromatography-ion mobility spectrometry filtered spectrum data were 91%~93% and the AUC value were 0.94~0.96. The positive judgment rate of models from Adaboost, decision tree (DT), KNN, MLP, SGD and SVM models based on gas chromatography-ion mobility spectrometry labeled substance data was 100%, and the AUC was 1.0, while the model evaluation index of RF model were 96% and 0.98, respectively. With near infrared spectrum and volatile compound characteristic data as important parameters for white tea grade evaluation, 6 and 10 kinds of grade discrimination models were built, which could accurately determine the grade of white tea, and the classifier algorithm was suitable for the modeling of these two types of data.

The present study aimed to optimize the ultrasonic wave and cellulase synergistic extraction technology of total flavonoids from Bambusae Caulis in Taeniam and evaluate their antioxidant capacity in vitro. Taking yield of total flavonoids as the metric, the appropriate amount of cellulase added, pH of extraction solvents, ethanol concentration, ultrasonic power, ultrasonic temperature, material-liquid ratio and ultrasonic time were scouted by single-factor experiments, and the optimal conditions for the extraction of total flavonoids from Bambusae Caulis in Taeniam were optimized by response surface methodology (RSM). Meanwhile, the antioxidant capacity was investigated in vitro using scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiaz-oline-6-sulfonic acid (ABTS) free radicals and iron ion reduction method (FRAP). As the result showed that the optimum extraction parameters were the amount of cellulase added: 5%, pH of extraction solvents: 4.7, ethanol concentration: 61%, ultrasonic power: 240 W, ultrasonic temperature: 60 ℃, material-liquid ratio: 1:30 (g/mL), ultrasonic time: 30 min. The total flavonoids yield of Bambusae Caulis in Taeniam was 0.83%±0.02% under these conditions, and the content of total flavonoids in Bambusae Caulis in Taeniam extract was 16.21%±0.42%. The results of antioxidant experiments showed that the total flavonoids could scavenge DPPH and ABTS+ radicals with IC50 values of 150.1 and 44.6 μg/mL, respectively, which were 1.22 and 1.27 times greater than VC. The ferric ion reducing ability of total flavonoids from Bambusae Caulis in Taeniam was slightly higher than that of VC. This optimized extraction process is simple and feasible, and the extracted total flavonoids shows strong antioxidant effects in vitro, which provides scientific evidence for the further study and exploit of flavonoids from Bambusae Caulis in Taeniam.

To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-RBD antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.

The properties of thermal sprayed WC based cermet coatings are limited by their structural defects, especially corrosion resistance. This article studied the influence of vacuum sealing with silicone resin on the long-term corrosion resistance of HVOF sprayed WC-Cr3C2-Ni coating in 3.5 wt.% NaCl solution. The surface morphologies of the unsealed and sealed coatings show the high compatibility between sealant and WC-Cr3C2-Ni coating. Benefiting from the block of sealant in defects, the sealed coating presents lower corrosion current density (5.843 × 10−8 A cm−2) after long-term corrosion than the unsealed coating (1.776 × 10−7 A cm−2). Owing to the vacuum treatment, sealant adequately penetrates and remains inside the WC-Cr3C2-Ni coating, and inhibits the growth of corrosion pits on the sealed coating surface. The vacuum sealing with silicone resin effectively hinders the diffusion of corrosion solution, and provides practicable strategy to improve the corrosion resistance of the coatings.

The unique sensory quality and health effect of Liupao tea are closely related to the participation of microorganisms in the pile-fermentation process. In order to explore the diversity and distribution of fungi in Liupao tea samples during the pile-fermentation and autoclaved process, traditional isolation and culture method and molecular biological identification technology were used to isolate and identify fungi from 14 samples including the Liupao raw tea, the samples of pile-fermentation process and those of autoclaved process in this study. The results were as follows: 13 genera and 39 species fungi were isolated and identified from the samples. Among them, 23 fungi were reported firstly in Liupao tea, including 3 species of golden flower fungi and 6 species of yeasts. Aspergillus and Penicillium were the dominant fungi genera in Liupao raw tea and the samples of pile-fermentation process. Only Aspergillus niger, Aspergillus sydowii, Penicillium laeve and Penicillium gerundense could be isolated from the samples after autoclaved, and other Aspergillus and Penicillium fungi were almost undetectable. Talaromyces was the dominant genus in the samples of autoclaved process. In terms of species, Aspergillus niger and Arxula adeninivorans were the dominant fungal in all tea samples. The results would enrich the cognition of fungal diversity during the processing of Liupao tea, and provide the material basis and theoretical basis for further exploring the effects of different tea source fungi on the quality of Liupao tea.

The bioactivity of tea polysaccharides (TPs) has been widely reported, but studies to date have focused on green tea. Some human health investigations have implied that black tea may possess potential antidiabetic effects, but less is known about their potential role and related antidiabetic mechanism. The present study was, therefore, conducted to investigate the chemical properties and antidiabetic activity of TPs from black tea. Monosaccharide composition revealed that Alduronic acid (77.8 mol%) considerably predominated in the fraction. TP conformation analysis indicated that three components in TPs were all typical of high-branching structures. Oral administration of TPs could effectively alleviate fasting blood glucose in type 2 diabetes mellitus (T2D) mice, with the values 23.6 ± 1.42, 19.6 ± 2.25, and 16.4 ± 2.07 mmol/L in the 200, 400, and 800 mg/kg·BW groups, respectively. Among these TPs groups, the 800 mg/kg·BW groups significantly decreased by 37.88% when compared with the T2D+water group (p < 0.05). Further studies demonstrated that TP treatment upregulated the expression of p-Akt/p-PI3K (p < 0.001). Additionally, TP treatment significantly promoted glucose transporter protein 2 (GLUT2) translocation in the liver (p < 0.001). These findings suggest that TPs from black tea protect against T2D by activating PI3K/Akt/GLUT2 signaling and might serve as a novel therapeutic candidate for T2D.

Berberine (BBR) as one of the most effective natural products has been increasingly used to treat various chronic diseases due to its immunosuppressive/tolerogenic activities. However, it is unknown if BBR can be applied without abrogating the efforts of vaccination. Here we show that priming of CD8+ T cells in the presence of BBR lead to improved central memory formation (Tcm) with substantially reduced effector proliferation, primarily orchestrated through activation of AMPK and Stat5. Tcm derived from vaccinated mice fed with BBR were able to adoptively transfer protective immunity to naïve recipients. Vaccination of BBR-fed mice conferred better memory protection against infection without losing immediate effector efficacy, suggesting appreciable benefits from using BBR in vaccination. Thus, our study may help to lay the groundwork for mechanistic understanding of the immunomodulatory effects of natural products and their potential use as adjuvant that allows the design of novel vaccines with more desirable properties.

To investigate the cryoprotective effect of tara gum on myofibrillar proteins, the influences of tara gum on the freezing curve of myofibrillar proteins of grass carp were studied using a commercial cryoprotectant (4% sucrose+4% sorbitol) as a control in this study. The effects of tara gum on the freezing stability of myofibrillar proteins during frozen storage (0~28 days) were investigated by assessing Ca2+-ATPase activity, sulfhydryl content, surface hydrophobicity, endogenous fluorescence spectra and water mobility. The results showed that the freezing temperature of myofibrillar proteins solution added with 1% tara gum and commercial cryoprotectant were −8.3 ℃ and −7.3 ℃, respectively, which were significantly lower than that of the control (−5.5 ℃). After 28 d of frozen storage, the Ca2+-ATPase activity, total sulfhydryl content, and active sulfhydryl content of myofibrillar proteins with the addition of 1% tara gum and commercial cryoprotectant decreased by 45.69% and 45.17%, 24.49% and 42.28%, 25.13% and 39.79%, and the surface hydrophobicity increased by 176.00% and 122.23%, respectively. The changes were significantly lower than those of the blank control. Additionally, the results of LF-NMR showed that the addition of 1% gum and commercial cryoprotectant significantly inhibited the increase of water mobility of myofibrillar protein solution after thawing. Therefore, the 1% tara gum could enhance the stability of myofibrillar proteins of grass carp during frozen storage.

In order to explore the mechanism of the influence of Sn contents on the relevant properties of Cu–Sn alloys, the structure, elasticity, electronic, and thermal properties of Cu–Sn alloys doped with different proportions of Sn (3.125 at%, 6.25 at%, and 9.375 at%) were established using the first-principles calculation based on density functional theory. Firstly, their lattice constants and Sn concentration comply with Vegard’s Law. From the mixing enthalpy, it can be seen that Sn atoms can be firmly dissolved in the Cu matrix, and the structure is most stable when the Sn content is 3.125 at%. In addition, the introduction of mismatch strain characterized their solid solution strengthening effect. The elastic and electronic properties showed that when the Sn content is 6.25 at%, the Cu–Sn alloy has the best plasticity and the highest elastic anisotropy; when the Sn content is 3.125 at%, the Cu–Sn alloy is the most stable and has stronger bulk and shear modulus, which was mainly due to a stronger Cu-Cu covalent bond. Finally, the Debye temperature, thermal conductivity, and melting point were calculated. It is estimated that the thermal conductivity of Cu–Sn alloy is relatively good when the Sn content is low.

This study investigated the changes of the sensory qualities of appearance, color, aroma, taste, leaf bottom and the chemical components of tea polyphenols, free amino acids, soluble sugar, caffeine, flavonoids, theabrownin (TB), theaflavin (TF) and thearubigin (TR) using the Liupao tea during processing and was produced by group species Zhongcha Tea Factory in Cangwu County, Wuzhou City, Guangxi, China. In addition, the chemical composition, and the antioxidant of the theabrownin (TB) that extracted from the Liupao tea were investigated. The results showed that the contents of water extract, tea polyphenols, thearubigin (TR), free amino acids and flavonoids were significantly decreased during the fermentation process (P40 d>60 d>20 d. The results of this study would provide a theoretical basis for the production and processing of Liupao tea.

The long non-coding RNA, Negative Regulator of Antiviral Response (NRAV) has been identified as a participant in both respiratory virus replication and immune checkpoints, however, its involvement in pan-cancer immune regulation and prognosis, particularly those of hepatocellular carcinoma (HCC), remains unclear. To address this knowledge gap, we analyzed expression profiles obtained from The Cancer Genome Atlas (TCGA) database, comparing normal and malignant tumor tissues. We found that NRAV expression is significantly upregulated in tumor tissues compared to adjacent nontumor tissues. Kaplan-Meier (K-M) analysis revealed the prognostic power of NRAV, wherein overexpression was significantly linked to reduced overall survival in a diverse range of tumor patients. Furthermore, noteworthy associations were observed between NRAV, immune checkpoints, immune cell infiltration, genes related to autophagy, epithelial-mesenchymal transition (EMT), pyroptosis, tumor mutational burden (TMB), and microsatellite instability (MSI) across different cancer types, including HCC. Moreover, NRAV upregulation expression was associated with multiple pathological stages by clinical observations. Furthermore, our investigation revealed a substantial elevation in the expression of NRAV in both HCC tumor tissues and cells compared to normal tissues and cells. The inhibition of NRAV resulted in the inhibition of cell proliferation, migration, and invasion in HCC cells, while also influencing the expression of CD274 (PD-L1) and CD44, along with various biomarkers associated with EMT, autophagy, and pyroptosis. The aforementioned results propose NRAV as a promising prognostic biomarker for HCC. [ABSTRACT FROM AUTHOR]

In this study, an enclosed cooling slope channel (ECSC) was used to produce a semi-solid slurry of the 7075 aluminum alloy. The effects of the pouring temperature and the rate of cooling water on the microstructure of the semi-solid slurry were studied. The microstructure, solidification behavior, mechanical properties, and fracture mechanism of rheological squeeze casting (Rheo-SC) and liquid squeeze casting (LSC) samples were compared. The results indicate that lowering the pouring temperature and increasing the rate of cooling water can refine the crystals of the semi-solid slurry. The best process is a pouring temperature of 670 °C and a rate of cooling water of 200 L/h. The microstructure of the LSC samples was made up of coarse dendritic crystals, but the microstructure of the Rheo-SC samples was made up of almost spherical primary α1-Al and refined secondary α2-Al under this method. The ultimate tensile strength, yield strength, and elongation of the Rheo-SC samples were 238 MPa, 151 MPa, and 5.2%, respectively, which were 10%, 10.5%, and 44.4% higher than those of the LSC sample. The key factor contributing to the increased performance of the Rheo-SC samples is the combination of decreased casting flaws, strengthened grain refinement, and improved segregation.

Abstract We have recently described Pz-1, a benzimidazole-based type-2 RET and VEGFR2 inhibitor. Based on a kinome scan, here we show that Pz-1 is also a potent (IC50

This paper presents the performance analysis of CentiSpace low earth orbit (LEO) experiment satellites. Distinguishing them from other LEO navigation augmentation systems, the co-time and co-frequency (CCST) self-interference suppression technique is employed in CentiSpace to mitigate significant self-interference caused by augmentation signals. Consequently, CentiSpace exhibits the capability of receiving navigation signals from the Global Navigation Satellite System (GNSS) while simultaneously broadcasting augmentation signals within the same frequency bands, thus ensuring excellent compatibility for GNSS receivers. CentiSpace is a pioneering LEO navigation system to successfully complete in-orbit verification of this technique. Leveraging the on-board experiment data, this study analyzes the performance of space-borne GNSS receivers equipped with self-interference suppression and evaluates the quality of navigation augmentation signals. The results show that CentiSpace space-borne GNSS receivers are capable of covering more than 90% visible GNSS satellites and the precision of self-orbit determination is at the centimeter level. Furthermore, the quality of augmentation signals meets the requirements outlined in the BDS interface control documents. These findings underscore the potential of the CentiSpace LEO augmentation system for the establishment of global integrity monitoring and GNSS signal augmentation. Moreover, these results contribute to subsequent research on LEO augmentation techniques.

Identifying the geographical origins of white tea is of significance because the quality and price of white tea from different production areas vary largely from different growing environment and climatic conditions. In this study, we used near-infrared spectroscopy (NIRS) with white tea (n = 579) to produce models to discriminate these origins under different conditions. Continuous wavelet transform (CWT), min-max normalization (Minmax), multiplicative scattering correction (MSC) and standard normal variables (SNV) were used to preprocess the original spectra (OS). The approaches of principal component analysis (PCA), linear discriminant analysis (LDA) and successive projection algorithm (SPA) were used for features extraction. Subsequently, identification models of white tea from different provinces of China (DPC), different districts of Fujian Province (DDFP) and authenticity of Fuding white tea (AFWT) were established by K-nearest neighbors (KNN), random forest (RF) and support vector machine (SVM) algorithms. Among the established models, DPC-CWT-LDA-KNN, DDFP-OS-LDA-KNN and AFWT-OS-LDA-KNN have the best performances, with recognition accuracies of 88.97%, 93.88% and 97.96%, respectively; the area under curve (AUC) values were 0.85, 0.93 and 0.98, respectively. The research revealed that NIRS with machine learning algorithms can be an effective tool for the geographical origin traceability of white tea.

Abstract Background Although observational epidemiological studies have found that smoking is positively associated with risk of rheumatoid arthritis (RA), assessing the causality of this relationship has remained elusive because conventional observational studies are susceptible to bias such as confounding and reverse causation. Here, we applied the Mendelian randomization (MR) approach to examine the potential causal relationship between smoking and risk of RA. Methods Summary statistics data for RA were obtained from a meta-analysis of genome-wide association studies (GWAS), including 14,361 RA cases and 43,923 controls of European ancestry. The instrumental variables (IV) and the genetic association estimates for smoking initiation and lifetime smoking were obtained from a GWAS meta-analysis including 1,232,091 individuals and a GWAS of 462,690 individuals of European ancestry, respectively. MR analyses were performed using the inverse-variance weighted (IVW) method and supplemented with the weighted-median method. Potential pleiotropy was assessed using the MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test and MR-Egger regression. Sensitivity analyses were further performed to test the robustness of the association. Results We found that compared with never smokers, genetic predisposition to smoking initiation was positively associated with risk of RA (odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.15–1.52, P = 9.17 × 10−5 using the IVW method). Similarly, genetically predicted lifetime smoking was associated with an increased risk of RA (OR = 1.55, 95% CI = 1.13–2.14, P = 0.007). Sensitivity analyses using alternative MR methods and different sets of IVs produced similar results, suggesting the robustness of our findings. Conclusions These results provide support for a causal association between smoking and increased risk of RA. Further studies are warranted to explain the underlying mechanisms of smoking in the development of RA.

Raffinose synthetase (RS) is a key enzyme in the process of raffinose (Raf) synthesis and is involved in plant development and stress responses through regulating Raf content. As a sweetener, Raf makes an important contribution to the sweet taste of white tea. However, studies on the identification, analysis and transcriptional regulation of CsRSs (Camellia sinensis RS genes) are still lacking. In this study, nine CsRSs were identified from the tea plant (Camellia sinensis) genome database. The CsRSs were classified into five groups in the phylogenetic tree. Expression level analysis showed that the CsRSs varied in different parts of the tea plant. Transcriptome data showed that CsRSs could respond to persistent drought and cold acclimation. Except for CsRS5 and CsRS9, the expression pattern of all CsRSs increased at 12 h and decreased at 30 h during the withering process of white tea, consistent with the change trend of the Raf content. Furthermore, combining yeast one-hybrid assays with expression analysis, we found that CsDBB could potentially regulate the expression of CsRS8. Our results provide a new perspective for further research into the characterization of CsRS genes and the formation of the white tea flavour.

Treatment of full-thickness articular cartilage defects with exposure of subchondral bone often seen in osteoarthritic conditions has long been a great challenge, especially with a focus on the feasibility of in situ cartilage regeneration through minimally invasive procedures. Osteoblasts that situate in the subchondral bone plate may be considered a potentially vital endogenous source of cells for cartilage resurfacing through direct reprogramming into chondrocytes. Microarray-based gene expression profiles were generated to compare tissue-specific transcripts between subchondral bone and cartilage of mice and to assess age-dependent differences of chondrocytes as well. On osteoblast cell lines established from mouse proximal tibial subchondral bone, sequential screening by co-transduction of transcription factor (TF) genes that distinguish chondrocytes from osteoblasts reveals a shortlist of potential reprogramming factors exhibiting combined effects in inducing chondrogenesis of subchondral bone osteoblasts. A further combinatorial approach unexpectedly identified two 3-TF combinations containing Sox9 and Sox5 that exhibit differences in reprogramming propensity with the third TF c-Myc or Plagl1, which appeared to direct the converted chondrocytes toward either a superficial or a deeper zone phenotype. Thus, our approach demonstrates the possibility of converting osteoblasts into two major chondrocyte subpopulations with two combinations of three genes (Sox9, Sox5, and c-Myc or Plagl1). The findings may have important implications for developing novel in situ regeneration strategies for the reconstruction of full-thickness cartilage defects.

Groundwater protection is essential for global sustainable development. Due to the lack of motivation among farmers to build harmless disposal facilities for livestock excrement, there is a huge challenge surrounding groundwater protection, which also threatens the achievement of the UN Sustainable Development Goal (SDG) 6: “clean water and sanitation”. Aiming to improve the groundwater protection behavior (GPB) of farmers, this study involved the following approach: (1) the use of rural China as a case area; (2) an exploration of the theoretical mechanisms and quantitative impacts of cooperatives as a way to encourage farmers to build harmless disposal facilities for livestock excrement; (3) a discussion about improvement strategies to increase the possibility of farmers building harmless disposal facilities for livestock excrement. The study highlighted the following findings: (1) compared to farmers who did not participate in cooperatives, farmers who were in cooperatives were 1.18% more likely to build harmless disposal facilities for livestock excrement; (2) compared to the basic scenario, the probability of farmers building harmless disposal facilities for livestock excrement could be increased by 50~1300%. The results of this study could help to provide a reference for the introduction of policies to protect groundwater, as well as an experiential reference for the achievement of the UN SDGs 3 and 6.