Unveiling biochar potential to promote safe crop production in toxic metal(loid) contaminated soil: A meta-analysis.

Biochar application emerges as a promising and sustainable solution for the remediation of soils contaminated with potentially toxic metal (loid)s (PTMs), yet its potential to reduce PTM accumulation in crops remains to be fully elucidated. In our study, a hierarchical meta-analysis based on 276 research articles was conducted to quantify the effects of biochar application on crop growth and PTM accumulation. Meanwhile, a machine learning approach was developed to identify the major contributing features. Our findings revealed that biochar application significantly enhanced crop growth, and reduced PTM concentrations in crop tissues, showing a decrease trend of grains (36.1%, 33.6-38.6%) > shoots (31.1%, 29.3-32.8%) > roots (27.5%, 25.7-29.2%). Furthermore, biochar modifications were found to amplify its remediation potential in PTM-contaminated soils. Biochar application was observed to provide favorable conditions for reducing PTM uptake by crops, primarily through decreasing available PTM concentrations and improving overall soil quality. Employing machine learning techniques, we identified biochar properties, such as surface area and C content as a key factor in decreasing PTM bioavailability in soil-crop systems. Furthermore, our study indicated that biochar application could reduce probabilistic health risks associated with of the presence of PTMs in crop grains, thereby contributing to human health protection. These findings highlighted the essential role of biochar in remediating PTM-contaminated lands and offered guidelines for enhancing safe crop production.

Sources and human health risks associated with potentially toxic elements (PTEs) in urban dust: A global perspective.

Long-term exposure to urban dust containing potentially toxic elements (PTEs) poses detrimental impacts on human health. However, studies estimating human health risks in urban dusts from a global perspective are scarce. We evaluated data for twelve PTEs in urban dusts across 59 countries from 463 published articles, including their concentrations, input sources, and probabilistic risks to human health. We found that 34.1 and 60.3% of those investigated urban dusts have been heavily contaminated with As and Cd, respectively. The input of PTEs was significantly correlated with economic structure due to emissions of industrial activities and traffic emissions being the major sources. Based on the Monte Carlo simulation, we found that the mean hazard index below the safe threshold (1.0) could still cause non-negligible risks to human health. Arsenic and Cr were the major PTEs threatening human health, and relatively high risk levels were observed in cities in China, Korea, Chile, Malaysia, and Australia. Importantly, our analysis suggested that PTEs threaten the health of approximately 92 million adults and 280 million children worldwide. Overall, our study provides important foundational understanding and guidance for policy decision-making to reduce the potential risks associated with PTE exposure and to promote sustainable development of urban economies.

[Mechanism of bulleyaconitine A in inhibiting bone destruction of rheumatoid arthritis via Src/PI3K/Akt signaling pathway].

Based on the sarcoma receptor coactivator(Src)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, the mechanism of action of bulleyaconitine A in the treatment of bone destruction of experimental rheumatoid arthritis(RA) was explored. Firstly, key targets of RA bone destruction were collected through GeneCards, PharmGKB, and OMIM databa-ses. Potential targets of bulleyaconitine A were collected using SwissTargetPrediction and PharmMapper databases. Next, intersection targets were obtained by the Venny 2.1.0 platform. Protein-protein interaction(PPI) network and topology analysis were managed by utilizing the STRING database and Cytoscape 3.8.0. Then, Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were conducted in the DAVID database. AutoDock Vina was applied to predict the molecular docking and binding ability of bulleyaconitine A with key targets. Finally, a receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model was established in vitro. Quantitative real-time polymerase chain reaction(qRT-PCR) was used to detect the mRNA expression levels of related targets, and immunofluorescence and Western blot were adopted to detect the protein expression level of key targets. It displayed that there was a total of 29 drug-disease targets, and Src was the core target of bulleyaconitine A in anti-RA bone destruction. Furthermore, KEGG enrichment analysis revealed that bulleyaconitine A may exert an anti-RA bone destruction effect by regulating the Src/PI3K/Akt signaling pathway. The molecular docking results showed that bulleyaconitine A had better bin-ding ability with Src, phosphatidylinositol-4,5-diphosphate 3-kinase(PIK3CA), and Akt1. The result of the experiment indicated that bulleyaconitine A not only dose-dependently inhibited the mRNA expression levels of osteoclast differentiation-related genes cathepsin K(CTSK) and matrix metalloproteinase-9(MMP-9)(P<0.01), but also significantly reduced the expression of p-c-Src, PI3K, as well as p-Akt in vitro osteoclasts(P<0.01). In summary, bulleyaconitine A may inhibit RA bone destruction by regulating the Src/PI3K/Akt signaling pathway. This study provides experimental support for the treatment of RA bone destruction with bulleyaconitine A and lays a foundation for the clinical application of bulleyaconitine A.

[Mechanism of Yuxuebi Tablets in treating synovial inflammation in rheumatoid arthritis based on transcriptomics].

This study investigated the mechanism of Yuxuebi Tablets(YXB) in the treatment of synovial inflammation in rheumatoid arthritis(RA) based on transcriptomic analysis. Transcriptome sequencing technology was employed to analyze the gene expression profiles of joint tissues from normal rats, collagen-induced arthritis(CIA) rats(an RA model), and YXB-treated rats. Common diffe-rentially expressed genes(DEGs) were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. RA synovial inflammation-related target genes were retrieved from the OMIM and GeneCards databases. Venny 2.1 software was used to identify the intersection of YXB target genes and RA synovial inflammation-related target genes, and GO and KEGG enrichment analyses were performed on the intersecting target genes. Immunohistochemistry was used to assess the protein expression levels of the inflammatory factors interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) in rat joint tissues. Western blot analysis was employed to measure the expression levels of key proteins in the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway. A total of 2 058 DEGs were identified by intersecting the genes from the normal group vs model group and the model group vs YXB treatment group. A search in OMIM and GeneCards databases yielded 1 102 RA synovial inflammation-related target genes. After intersecting with the DEGs in the YXB treatment group, 204 intersecting target genes were identified, primarily involving biological processes such as immune response, signal transduction, and inflammatory response; cellular components including plasma membrane, extracellular space, and extracellular region; molecular functions like protein binding, identical protein binding, and receptor binding. These target genes were mainly enriched in signaling pathways such as PI3K/Akt, cytokine-cytokine receptor interaction, and Janus kinase/signal transducer and activator of transcription(JAK/STAT). Western blot results showed that YXB at low, medium, and high doses could significantly inhibit the expression levels of key proteins in the PI3K/Akt signaling pathway in rat joint tissues in a dose-dependent manner. Immunohistochemistry further confirmed these findings, showing that YXB not only suppressed the protein expression levels of the inflammatory factors IL-1ß and TNF-α in the joint synovial tissues of CIA rats, but also inhibited p-Akt protein expression. In conclusion, this study used transcriptomic analysis to uncover the key mechanisms of YXB in inhibiting synovial inflammation and alleviating the progression of RA, with a focus on its role in suppressing the PI3K/Akt signaling pathway.

Meta-analysis of impacts of microplastics on plant heavy metal(loid) accumulation.

The co-occurrence of microplastics (MPs) and heavy metal(loid)s (HMs) has attracted growing scientific interest because of their wide distribution and environmental toxicity. Nevertheless, the interactions between MPs and HMs in soil-plant systems remain unclear. We conducted a meta-analysis with 3226 observations from 87 independent studies to quantify the impact of MPs addition on the plant biomass and HMS accumulation. Co-occurrence of MPs and HMs (except for As) induced synergistic toxicity to plant growth. MPs promoted their uptake in the shoot by 11.0% for Cd, 30.0% for Pb, and 47.1% for Cu, respectively. In contrast, MPs caused a significant decrease (22.6%, 17.9-26.9%) in the shoot As accumulation. The type and dose of MPs were correlated with the accumulation of HMs. MPs increased available concentrations of Cd, Pb, and Cu, but decreased available As concentration in soils. Meanwhile, MPs addition significantly lowered soil pH. These findings may provide explanations for MPs-mediated effects on influencing the accumulation of HMs in plants. Using a machine learning approach, we revealed that soil pH and total HMs concentration are the major contributors affecting their accumulation in shoot. Overall, our study indicated that MPs may increase the environmental risks of HMs in agroecosystems, especially metal cations.

Blocking of FGFR4 signaling by F30 inhibits hepatocellular carcinoma cell proliferation through HMOX1-dependent ferroptosis pathway.

Excessive activation of FGF19/fibroblast growth factor receptor 4 (FGFR4) signaling is associated with poor survival of patients with hepatocellular carcinoma (HCC). FGFR4 inhibitors show promise for HCC treatment. F30, an indazole derivative designed through computer-aided drug design targeting FGFR4, demonstrated anti-HCC activity as described in our previous studies. However, the precise molecular mechanisms underlying F30's anticancer effects remain largely unexplored. We report here that F30 could effectively induce ferroptosis in HCC cells. The concentrations of cellular ferrous iron, the peroxidation of cell membranes and the homeostasis of reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG) were dysregulated by F30, thereby affecting cellular redox status. Induction of ferroptosis in HCC by F30 was inhibited by specific ferroptosis inhibitor ferrostatin-1. F30 upregulates various ferroptosis-related genes, including the heme oxygenase enzymes 1 (HMOX1), a key mediator of redox regulation. Surprisingly, F30-induced ferroptosis in HCC is dependent on HMOX1. The dysregulation of cellular ferrous iron concentrations and cell membrane peroxidation was rescued when knocking down HMOX1 with specific small interfering RNA. These findings shed light on the molecular mechanisms underlying FGFR4-targeting F30's anti-HCC effects and suggest that FGFR4 inactivation could be beneficial for HCC treatment involving ferroptosis.

Vertical migration behavior simulation and prediction of Pb and Cd in co-contaminated soil around Pb-Zn smelting slag site.

Heavy metal migration in soil poses a serious threat to the soil and groundwater. Understanding the migration pattern of heavy metals (HMs) under different factors could provide a more reasonable position for pollution evaluation and targetoriented treatment of soil heavy metal. In this study, the migration behavior of Pb and Cd in co-contaminated soil under different pH and ionic strength (NaCl concentration) was simulated using convective dispersion equation (CDE). We predicted the migration trends of Pb and Cd in soils after 5, 10, and 20 years via PHREEQC. The results showed that the migration time of Cd in the soil column experiment was about 60 days faster than that of Pb, and the migration trend was much steeper. The CDE was proved to describe the migration behavior of Pb and Cd (R2 > 0.75) in soil. The predicted results showed that Cd migrated to 15-20 cm of soil within 7 years and Pb stayed mainly in the top 0-6 cm of soil within 5 years as the duration of irrigation increased. Overall, our study is expected to provide new insight into the migration of heavy metal in soil ecosystems and guidance for reducing risk of heavy metal in the environment.

Discovering and Validating Cuproptosis-Associated Marker Genes for Accurate Keloid Diagnosis Through Multiple Machine Learning Models.

Background: Keloid is a common condition characterized by abnormal scarring of the skin, affecting a significant number of individuals worldwide. Objective: The occurrence of keloids may be related to the reduction of cell death. Recently, a new cell death mode that relies on copper ions has been discovered. This study aimed to identify novel cuproptosis-related genes that are associated with keloid diagnosis. Methods: We utilized several gene expression datasets, including GSE44270 and GSE145725 as the training group, and GSE7890, GSE92566, and GSE121618 as the testing group. We integrated machine learning models (SVM, RF, GLM, and XGB) to identify 10 cuproptosis-related genes (CRGs) for keloid diagnosis in the training group. The diagnostic capability of the identified CRGs was validated using independent datasets, RT-qPCR, Western blotting, and IHC analysis. Results: Our study successfully categorized keloid samples into two clusters based on the expression of cuproptosis-related genes. Utilizing WGCNA analysis, we identified 110 candidate genes associated with cuproptosis. Subsequent functional enrichment analysis results revealed that these genes may play a regulatory role in cell growth within keloid tissue through the MAPK pathway. By integrating machine learning models, we identified CRGs that can be used for diagnosing keloid. The diagnostic efficacy of CRGs was confirmed using independent datasets, RT-qPCR, Western blotting, and IHC analysis. GSVA analysis indicated that high expression of CRGs influenced the gene set related to ECM receptor interaction. Conclusion: This study identified 10 cuproptosis-related genes that provide insights into the molecular mechanisms underlying keloid development and may have implications for the development of targeted therapies.

Silicon reduces toxicity and accumulation of arsenic and cadmium in cereal crops: A meta-analysis, mechanism, and perspective study.

Arsenic (As) and cadmium (Cd) are two toxic metal(loid)s that pose significant risks to food security and human health. Silicon (Si) has attracted substantial attention because of its positive effects on alleviating the toxicity and accumulation of As and Cd in crops. However, our current knowledge of the comprehensive effects and detailed mechanisms of Si amendment is limited. In this study, a global meta-analysis of 248 original articles with over 7000 paired observations was conducted to evaluate Si-mediated effects on growth and As and Cd accumulation in rice (Oryza sativa L.), wheat (Triticum aestivum L.), and maize (Zea mays L.). Si application increases the biomass of these crops under As and/or Cd contamination. Si amendment also decreased shoot As and Cd accumulation by 24.1 % (20.6 to 27.5 %) and 31.9 % (29.0 to 31.9 %), respectively. Furthermore, the Si amendment reduced the human health risks posed by As (2.6 %) and Cd (12.9 %) in crop grains. Si-induced inhibition of Cd accumulation is associated with decreased Cd bioavailability and the downregulation of gene expression. The regulation of gene expression by Si addition was the driving factor limiting shoot As accumulation. Overall, our analysis demonstrated that Si amendment has great potential to reduce the toxicity and accumulation of As and/or Cd in crops, providing a scientific basis for promoting food safety globally.

Correlating facial skin parameters with age and gender in population of Shaanxi Province, China.

OBJECTIVE: This study was designed to comprehensively evaluate the changes in facial skin biophysical parameters with age, as well the influence of gender differences in populations of Shaanxi Province, China. METHODS: Fourteen skin parameters, including stratum corneum hydration (SCH), transdermal water loss (TEWL), erythema, melanin, R0, R2, R5, R7, F4, gloss, skin surface pH, skin erythema index (a*), wrinkle length, and sebum, were measured by noninvasive instruments in 481 volunteers from Shaanxi Province. Spearman correlation analysis was performed to analyze the relationship between skin parameters and age. Additionally, skin parameters were analyzed for different age groups and different genders. RESULTS: The results of the study showed a linear decrease in skin surface pH and sebum content with age, and the skin elasticity parameters R0, R2, R5, and R7 decreased significantly at the age of 54-65 years. Wrinkle length showed a linear and increase with age. R5 showed a weak negative correlation with age, R2, R7, and sebum content showed a moderate negative correlation, while wrinkle length showed a strong positive correlation. Considering the effect of gender on skin parameters, the results showed that SCH and gloss were lower in men than in women, while TEWL, erythema, melanin, wrinkle length, and sebum were higher than in women. However, there was no difference in skin elasticity between them. CONCLUSION: The facial skin parameters, especially for the wrinkle length, exhibited the strong correlation relationship with ages in Shaanxi Province. Meanwhile, most skin parameters show significant differences with gender, which can provide a reference for future research and development in the field of cosmetics.

Effects of four amendments on cadmium and arsenic immobilization and their exposure risks from pakchoi consumption.

Exposure to heavy metal(loid)s (HM) through contaminated food chains poses significant health risks to humans. While soil amendments are known to reduce HM bioavailability, their effects on bioaccessibility and health risks in soil-pakchoi-human systems remain unclear. To address this knowledge gap, we conducted a greenhouse pot experiment coupling soil immobilization with bioaccessibility-based health risk assessment for Cd and As exposure from pakchoi consumption. Four amendments (attapulgite, shell powder, nanoscale zero-valent iron, and biochar) were applied to soil, resulting in changes to soil characteristics (pH and organic matter), plant dry weight, and exchangeable fractions of As and Cd. Among the tested amendments, biochar exhibited the highest effectiveness in reducing the risk of Cd and As exposure from pakchoi consumption. The bioaccessibility-based health risk assessment revealed that the application of 5% biochar resulted in the lowest hazard index, significantly decreasing it from 1.36 to 0.33 in contaminated soil. Furthermore, the structural equation model demonstrated that pH played a critical role in influencing remediation efficiency, impacting the exposure of the human body to Cd and As. In conclusion, our study offers a new perspective on mitigating exposure risks of soil HM and promoting safe crop production. The results underscore the importance of considering bioaccessibility in health risk assessment and highlight the potential of biochar as a promising amendment for reducing Cd and As exposure from pakchoi consumption.

[Intervention effect of Qufeng Gutong Cataplasm on myofascial pain syndrome in rats and its mechanism].

This paper aims to investigate the intervention effect of Qufeng Gutong Cataplasm(QFGT) on myofascial pain syndrome(MPS) in rats and to preliminarily explain its mechanism from the perspective of improving muscle inflammation and pain. Male SD rats were divided into 6 groups, namely normal group, model group, positive control drug(Huoxue Zhitong Ointment, HXZT) group, and low, medium, and high-dose QFGT groups(75, 150, and 300 mg·d~(-1)). The rat model of MPS was established by striking combined with centrifugation for 8 weeks, during which QFGT and HXZT were used for corresponding intervention. Standard VonFrey fiber was used to evaluate the mechanical pain threshold, and acetone was used to detect the cold pain threshold. The electrophysiological activity of muscle at trigger point was detected, and the electromuscular analysis of trigger point was performed. CatWalk gait analyzer was used to detect pain-induced gait adaptation changes. The hematoxylin-eosin(HE) staining was used to observe the pathological changes in muscle and skin tissues at the trigger point of rats. Immunohistochemistry was used to detect the expression of capsaicin receptor transient receptor potential vanilloid 1(TRPV1) in muscle tissues and interleukin(IL)-33 in skin tissues at the trigger point. The protein expression levels of TRPV1, protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), IL-1ß, and tumor necrosis factor-α(TNF-α) in muscle tissues at the trigger point were detected by Western blot. The results showed that as compared with the model group, the mechanical pain threshold and cold pain threshold of rats in other groups were increased after treatment with QFGT. The spontaneous electromyography(EMG) activity was observed in the model group, but QFGT alleviated the EMG activity in a dose-dependent manner. Gait analysis showed that standing duration, average intensity, swing speed, maximum contact point, maximum contact area, paw print length, paw print width, and paw print area were significantly improved in all QFGT groups. Pathological results showed that the disorder of muscle arrangement at the trigger point was decreased, muscle fiber adhesion and atrophy were reduced, and inflammatory cell infiltration was alleviated after treatment with QFGT. In addition, QFGT and HXZT both inhibited the protein expression of TRPV1, PI3K, Akt, p-Akt, IL-1ß, and TNF-α in the muscle tissues of rats with MPS. However, there was no significant difference in the pathological structure and expression of IL-33 in the treated skin as compared with the normal group. The related results have proved that QFGT can inhibit the release of inflammatory factors by inhibiting the TRPV1/PI3K/Akt signaling pathway in the muscle trigger point of rats with MPS and finally attenuate the atrophy and adhesion of local muscles and inflammatory infiltration, thereby relieving the muscle pain of rats with MPS, and local administration has no skin irritation.

A tumor mutational burden-derived immune computational framework selects sensitive immunotherapy/chemotherapy for lung adenocarcinoma populations with different prognoses.

Background: Lung adenocarcinoma (LUAD) kills millions of people every year. Recently, FDA and researchers proved the significance of high tumor mutational burden (TMB) in treating solid tumors. But no scholar has constructed a TMB-derived computing framework to select sensitive immunotherapy/chemotherapy for the LUAD population with different prognoses. Methods: The datasets were collected from TCGA, GTEx, and GEO. We constructed the TMB-derived immune lncRNA prognostic index (TILPI) computing framework based on TMB-related genes identified by weighted gene co-expression network analysis (WGCNA), oncogenes, and immune-related genes. Furthermore, we mapped the immune landscape based on eight algorithms. We explored the immunotherapy sensitivity of different prognostic populations based on immunotherapy response, tumor immune dysfunction and exclusion (TIDE), and tumor inflammation signature (TIS) model. Furthermore, the molecular docking models were constructed for sensitive drugs identified by the pRRophetic package, oncopredict package, and connectivity map (CMap). Results: The TILPI computing framework was based on the expression of TMB-derived immune lncRNA signature (TILncSig), which consisted of AC091057.1, AC112721.1, AC114763.1, AC129492.1, LINC00592, and TARID. TILPI divided all LUAD patients into two populations with different prognoses. The random grouping verification, survival analysis, 3D PCA, and ROC curve (AUC=0.74) firmly proved the reliability of TILPI. TILPI was associated with clinical characteristics, including smoking and pathological stage. Furthermore, we estimated three types of immune cells threatening the survival of patients based on multiple algorithms. They were macrophage M0, T cell CD4 Th2, and T cell CD4 memory activated. Nevertheless, five immune cells, including B cell, endothelial cell, eosinophil, mast cell, and T cell CD4 memory resting, prolonged the survival. In addition, the immunotherapy response and TIDE model proved the sensitivity of the low-TILPI population to immunotherapy. We also identified seven intersected drugs for the LUAD population with poor prognosis, which included docetaxel, gemcitabine, paclitaxel, palbociclib, pyrimethamine, thapsigargin, and vinorelbine. Their molecular docking models and best binding energy were also constructed and calculated. Conclusions: We divided all LUAD patients into two populations with different prognoses. The good prognosis population was sensitive to immunotherapy, while the people with poor prognosis benefitted from 7 drugs.

Evaluation of mulberry leaves' hypoglycemic properties and hypoglycemic mechanisms.

The effectiveness of herbal medicine in treating diabetes has grown in recent years, but the precise mechanism by which it does so is still unclear to both medical professionals and diabetics. In traditional Chinese medicine, mulberry leaf is used to treat inflammation, colds, and antiviral illnesses. Mulberry leaves are one of the herbs with many medicinal applications, and as mulberry leaf study grows, there is mounting evidence that these leaves also have potent anti-diabetic properties. The direct role of mulberry leaf as a natural remedy in the treatment of diabetes has been proven in several studies and clinical trials. However, because mulberry leaf is a more potent remedy for diabetes, a deeper understanding of how it works is required. The bioactive compounds flavonoids, alkaloids, polysaccharides, polyphenols, volatile oils, sterols, amino acids, and a variety of inorganic trace elements and vitamins, among others, have been found to be abundant in mulberry leaves. Among these compounds, flavonoids, alkaloids, polysaccharides, and polyphenols have a stronger link to diabetes. Of course, trace minerals and vitamins also contribute to blood sugar regulation. Inhibiting alpha glucosidase activity in the intestine, regulating lipid metabolism in the body, protecting pancreatic -cells, lowering insulin resistance, accelerating glucose uptake by target tissues, and improving oxidative stress levels in the body are some of the main therapeutic properties mentioned above. These mechanisms can effectively regulate blood glucose levels. The therapeutic effects of the bioactive compounds found in mulberry leaves on diabetes mellitus and their associated molecular mechanisms are the main topics of this paper's overview of the state of the art in mulberry leaf research for the treatment of diabetes mellitus.

[Mechanism of artesunate on bone destruction in experimental rheumatoid arthritis based on transcriptomics and network pharmacology].

The present study investigated the mechanism of artesunate in the treatment of bone destruction in experimental rheumatoid arthritis(RA) based on transcriptomics and network pharmacology. The transcriptome sequencing data of artesunate in the inhibition of osteoclast differentiation were analyzed to obtain differentially expressed genes(DEGs). GraphPad Prism 8 software was used to plot volcano maps and heat maps were plotted through the website of bioinformatics. GeneCards and OMIM were used to collect information on key targets of bone destruction in RA. The DEGs of artesunate in inhibiting osteoclast differentiation and key target genes of bone destruction in RA were intersected by the Venny 2.1.0 platform, and the intersection target genes were analyzed by Gene Ontology(GO)/Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment. Finally, the receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model and collagen-induced arthritis(CIA) model were established. Quantitative real time polymerase chain reaction(q-PCR), immunofluorescence, and immunohistochemistry were used to verify the pharmacological effect and molecular mechanism of artesunate in the treatment of bone destruction in RA. In this study, the RANKL-induced osteoclast differentiation model in vitro was established and intervened with artesunate, and transcriptome sequencing data were analyzed to obtain 744 DEGs of artesunate in inhibiting osteoclast differentiation. A total of 1 291 major target genes of bone destruction in RA were obtained from GeneCards and OMIM. The target genes of artesunate in inhibiting osteoclast differentiation and the target genes of bone destruction in RA were intersected to obtain 61 target genes of artesunate against bone destruction in RA. The intersected target genes were analyzed by GO/KEGG enrichment. According to the results previously reported, the cytokine-cytokine receptor interaction signaling pathway was selected for experimental verification. Artesunate intervention in the RANKL-induced osteoclast differentiation model showed that artesunate inhibited CC chemokine receptor 3(CCR3), CC chemokine receptor 1(CCR1) and leukemia inhibitory factor(LIF) mRNA expression in osteoclasts in a dose-dependent manner compared with the RANKL-induced group. Meanwhile, the results of immunofluorescence and immunohistochemistry showed that artesunate could dose-dependently reduce the expression of CCR3 in osteoclasts and joint tissues of the CIA rat model in vitro. This study indicated that artesunate regulated the CCR3 in the cytokine-cytokine receptor interaction signaling pathway in the treatment of bone destruction in RA and provided a new target gene for the treatment of bone destruction in RA.

A systematic review and meta-analysis of the seroconversion rates and adverse effects of COVID-19 mRNA vaccine and COVID-19 viral vector vaccine in kidney transplant recipient patients.

Patients received kidney transplantation (KTR) have a low seroconversion rate after vaccination. Our objective was to compare the seroconversion rates and adverse effects of additional different vaccinations in KTR patients in existing studies. Databases such as PubMed, Cochrane Library, Web of Science, Embase, ClinicalTrials.gov and others. Three high-quality RCT were included and showed no statistical difference in seroconversion rates between the two vaccines (RR = 0.93[0.76,1.13]). There was no statistical difference in seroconversion rates between the sexes, for men (RR = 0.93[0.69,1.25]) and women (RR = 0.91[0.62,1.33]). Among the adverse effects there was no statistically significant difference in fever (RR = 1.06[0.44,2.57]), while for injection site pain there was a statistically significant difference (RR = 1.14[1.18,1.84]). There was no significant difference in seroconversion rates in patients with KTR who received the two additional vaccines. Patients injected with the viral vector vaccine were less painful than those injected with the mRNA vaccine.

Contamination characteristics and source analysis of potentially toxic elements in dustfall-soil-crop systems near non-ferrous mining areas of Yunnan, southwestern China.

Potentially toxic elements (PTEs) in the dustfall-soil-crop system pose a serious threat to the ecological environment and agricultural production. However, there is still a knowledge gap in terms of better understanding the distinctive sources of PTEs by integrating various models and technologies. In this study, we comprehensively investigated the concentrations, distribution, and sources of seven PTEs in a dustfall-soil-crop system (424 samples in total) near a typical non-ferrous mining area, using absolute principal component score/multiple linear regression (APCS/MLR) combined with X-ray diffraction (XRD) and microscopy techniques. Our results showed that the mean values of As, Cd, Cr, Cu, Ni, Pb, and Zn in the soils were 211, 14, 105, 91, 65, 232, and 325 mg/kg, respectively. These values were significantly higher than the background soil values in Yunnan. Except for Ni and Cr, all elements in the soil were significantly higher than the screening values of agricultural lands in China. The spatial distribution of PTE concentrations was similar among the three media. The ACPS/MLR, XRD, and microscopy analyses further indicated that soil PTEs mainly originated from industrial activities (37 %), vehicle emissions and agricultural activities (29 %), respectively. Dustfall PTEs mainly originated from vehicle emissions and industrial activities, accounting for 40 % and 37 %, respectively. Crop PTEs mainly originated from vehicle emissions and soil (57 %), and agricultural activities (11 %), respectively. PTEs seriously threaten the safety of agricultural products and the ecological environment once they settle from the atmosphere to soil and crop leaves, further accumulate in crops, and spread through the food chain. Therefore, our study provides scientific evidence for government regulators to control PTE pollution and reduce their environmental risks in dustfall-soil-crop systems.

Microplastics may increase the environmental risks of Cd via promoting Cd uptake by plants: A meta-analysis.

Microplastics (MPs) and cadmium (Cd) are widely distributed in soil ecosystems, posing a potential threat to agricultural production and human health. However, the coupled effects of MPs and Cd in soil-plant systems remain largely unknown, especially on a large scale. In this study, a meta-analysis was conducted to evaluate the influence of MPs on plant growth and Cd accumulation under the Cd contamination conditions. Our results showed that MPs had significantly negative effects on shoot biomass (a decrease of 11.8 %) and root biomass (a decrease of 8.79 %). MPs also significantly increased Cd accumulation in the shoots and roots by 14.6 % and 13.5 %, respectively, revealing that MPs promote plant Cd uptake. Notably, polyethylene displayed a stronger promoting effect (an increase of 29.4 %) on Cd accumulation among these MP types. MPs induced a significantly increase (9.75 %) in concentration of soil available Cd and a slight decrease in soil pH, which may be the main driver promoting plant Cd uptake. MP addition posed physiological toxicity risks to plants by inhibiting photosynthesis and enhancing oxidative damage, directly demonstrating that MPs in combination with Cd can pose synergetic toxicity risks to plants. We further noted that MPs altered microbial diversity, likely influencing Cd bioavailability in soil-plant systems. Overall, our study has important implications for the combined impacts of Cd and MPs on plants and provides new insights into developing guidelines for the sustainable use of MPs in agriculture.