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BACKGROUND: People are exposed to metals in various ways during their daily lives. However, the association between metal exposure and gallstones remains unclear. OBJECTIVES: To investigate the relationship between serum elemental concentrations and the risk of gallstones. METHODS: Participants (n = 4204) were drawn from the Henan Rural Cohort. Gallstone diagnosis was based on abdominal ultrasound reports during follow-up. Baseline serum elemental concentrations were measured using inductively coupled plasma mass spectrometry. The relationship between serum elemental levels and gallstones was evaluated using robust Poisson regression, restricted cubic spline (RCS), quantile g-computation (Qgcomp), grouped weighted quantile sum (GWQS) and Bayesian kernel machine regression (BKMR). RESULTS: 121 individuals were diagnosed with gallstone (incidence rate of 2.88 %). In robust Poisson regression, after adjusting for confounding factors, the highest quartile of arsenic concentration compared to the lowest quartile had a 1.90 times higher relative risk (RR) [95 % confidence interval (CI): 1.05, 3.44]. Conversely, the highest quartile of zinc concentration compared to the lowest quartile had a 0.50 times lower RR (95 % CI: 0.28, 0.89). RCS showed an approximately "S"-shaped nonlinear relationship between serum arsenic levels and gallstones, with increasing arsenic concentration leading to a higher risk of gallstones; however, the risk plateaued when arsenic concentration exceeded 0.62 µg/L. Both the Qgcomp and GWQS indicated that arsenic plays a significant role in increasing the risk of gallstones, whereas zinc plays a significant role in reducing the risk of gallstones. BKMR showed that raising arsenic exposure from the 25th to the 75th percentile increased the risk of gallstones, while raising serum zinc concentration reduced it. CONCLUSIONS: Higher serum arsenic concentration increases the risk of gallstones, whereas higher zinc concentration may reduce the risk. Effective prevention of gallstones may require further reduction of arsenic exposure and appropriate increases in zinc intake.
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This study examines the economic impact of soaring international energy prices during the Russia-Ukraine conflict from February 23, 2022, to May 31, 2022. Notably, by applying a CGE model, this study offers insights into energy policies at both macroeconomic and industrial levels, emphasizing the model's utility in analyzing complex economic interactions under geopolitical stress. Findings indicate that: (1) Russia, a critical energy-producing country, faced severe economic setbacks due to sanctions, with its GDP contracting by 5.5 %, household income decreasing by 4 %, and consumer spending dropping by 3.5 %. This was accompanied by a significant reduction in domestic investment by 6 %, a decline in output by 5 %, and a decrease in societal welfare indicators. (2) Other energy-producing countries or regions, such as the Middle Eastern oil-producing countries, Australia, Canada, Mexico, and Southeast Asia, experienced economic benefits from the global energy market's "crowding-out effect." These regions saw an increase in GDP ranging from 2 % to 4.5 %, output growth by 3 %-6 %, and household income and consumption improvements by approximately 3 %-5 %. However, these benefits were tempered by a 1 %-2.5 % decline in domestic investment due to rising local energy costs. (3) Developed and developing regions, suffered adverse impacts, including the US, UK, EU, Japan, China, South Asia, Middle Eastern non-oil-producing countries, and Africa. These regions reported a decrease in GDP by 0.5 %-3 %, a decline in household income by 2 %-4 %, and lower consumption rates by 1.5 %-3.5 %. The economic strain was further exacerbated by an inflation increase of up to 2 % across these economies. This research offers valuable insights for governments and policymakers globally to address the challenges posed by the Ukraine crisis-induced energy crisis, underscoring the need for strategic energy policy adjustments and economic resilience planning.
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The efficient utilization of residual sludge and the rapid cultivation of aerobic granular sludge in continuous-flow engineering applications present significant challenges. In this study, aerobic granular cultivation was fostered in a continuous-flow system using Ca(ClO)2-sludge carbon (Ca-SC). Ca-SC retained the original sludge properties, contributing to granular growth in an A/O bioreactor. By day 40, the granule diameters increased to 0.8 mm with the SVI30 decreased by 2.7 times. Moreover, Ca-SC facilitated protein secretion, reaching 98.06 mg/g VSS and enhanced the hydrophobicity to 68.4 %. The continuous-flow aerobic granular sludge exhibited a nutrient removal rate above 90 %. Furthermore, Tessaracoccus and Nitrospira were enriched to promote granular formation and nitrogen removal. The residual sludge was carbonized and reused in the traditional wastewater treatment process to culture granular sludge in situ, aiming to achieve "self-production and self-consumption" of sludge and promote the innovative model of "treating waste with waste" in urban sewage environmental restoration.
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Reatores Biológicos , Esgotos , Esgotos/microbiologia , Aerobiose , Nitrogênio , Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos , Cloreto de Cálcio/farmacologiaRESUMO
Nitrogen (N) and carbon (C) inputs substantially affect soil microbial functions. However, the influences of long-term N and C additions on soil microbial resource limitation and heterotrophic respiration-fundamental microbial functional traits-remain unclear, impeding the understanding of how soil C dynamics respond to global change. In this study, the responses of soil microbial resource limitation and heterotrophic respiration (Rh) to 7-year N and biochar (BC) additions in a subtropical Moso bamboo (Phyllostachys edulis) plantation were investigated. We used eight treatments: Control, no N and BC addition; N30, 30 kg N (ammonium nitrate)·hm-2·a-1; N60, 60 kg N·hm-2·a-1; N90, 90 kg N·hm-2·a-1; BC20, 20 t BC (originating from Moso bamboo chips) hm-2; N30 + BC20, 30 kg N·hm-2·a-1 + 20 t BC hm-2; N60 + BC20, 60 kg N·hm-2·a-1 + 20 t BC hm-2; and N90 + BC20, 90 kg N·hm-2·a-1 + 20 t BC hm-2. Soil microbes were co-limited by N and phosphorus (P) and not limited by C in the control treatments. Long-term N addition enhanced soil microbial N and P limitation but significantly reduced soil Rh by 15.1 %-20.0 % relative to that in the control treatments. BC amendment alleviated soil microbial N and P limitation and significantly decreased C use efficiency by 10.9 %-42.1 % but increased Rh by 33.6 %-91.6 % in the long-term N-free and N-supplemented treatments (P < 0.05). Soil C- and N-acquisition enzyme activities were the dominant drivers of soil microbial resource limitation. Furthermore, microbial resource limitation was a more reliable predictor of Rh than soil resources or microbial biomass. The results suggested that long-term N and BC additions affect Rh by regulating microbial resource limitation, highlighting its significance in understanding soil C cycling under environmental change.
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The clinical incidence of sjogren's syndrome combined with gastroesophageal reflux disease is high. Existing observational studies have shown inconsistent results in the association between gastroesophageal reflux disease (GERD) and Sjogren's syndrome (SS).We observed that the symptoms of SS patients also improved after receiving GERD-related treatment. Therefore, we aimed to investigate the relationship between GERD and SS through a bidirectional two-sample Mendelian randomization (MR) study. Independent SNPs associated with GERD and SS were selected from a genome-wide association study (GWAS) as instrumental variables to conduct a bidirectional two-sample Mendelian analysis of GERD and SS. Genetic data were obtained from two databases for the following two outcomes: Gastroesophageal reflux (IEU Open GWAS) [sample size = 602,604 (patients = 129,080; nonpatients = 473,524)] and SS (FinnGen) [sample size = 392,423 (patients = 2,495; nonpatients = 389,928)]. Statistical methods for the MR analysis included the inverse-variance weighting method, weighted median, simple mode and weighted mode, as well as heterogeneity and sensitivity analyses using the Cochran Q statistic, MRâEgger regression, outlier detection methods (MR-PRESSO). In addition, Steiger Test was conducted to test the direction of causality. MR analysis showed a positive correlation between GERD and SS risk [odds ratio (OR) = 1.3279 (95% confidence interval 1.0312-1.7099, P = 0.0280)]. However, in contrast, no significant causal effect of SS on GERD was observed [OR = 1.0024 (95% CI 0.9651-1.0412; P = 0.8995)]. This bidirectional two-sample Mendelian randomization study confirmed a causal relationship between SS and GERD, and suggested that GERD is a risk factor for SS, while SS does not affect GERD.
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Refluxo Gastroesofágico , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Síndrome de Sjogren , Humanos , Refluxo Gastroesofágico/genética , Síndrome de Sjogren/genética , Síndrome de Sjogren/complicações , Predisposição Genética para Doença , FemininoRESUMO
BACKGROUND: Fewer studies have examined the relationship between air pollution and depressive or anxiety symptoms in rural residents. Social economic status (SES), as an important indicator of the current state of socioeconomic development, we know little about how it modifies the relationship between air pollution and symptoms of depression or anxiety. METHODS: The patient health questionnaire (PHQ-2) and generalized anxiety scale (GAD-2) were used to learn about the prevalence of depressive and anxiety symptoms, the social economic status of the participants was categorized into two levels: lower and higher, and a binary logistic regression model was used to analyze the relationship between air pollution and residents' symptoms of depression or anxiety. RESULTS: A total of 10,670 adults were enrolled in this study, of which a total of 1292 participants suffered from depressive symptoms and 860 suffered from anxiety symptoms. Short-term exposure to PM2.5 and O3, singly or in combination, may be associated with the onset of depression symptoms, and there was a significant interaction between SES and exposure to PM2.5 or O3. Residents of areas with higher SES may have a lower risk of suffering from anxiety symptoms after O3 exposure compared to participants living in lower SES. LIMITATIONS: The study was a cross-sectional study, which may have lowered the quality level of the evidence. CONCLUSIONS: Short-term PM2.5 and O3 exposure may be associated with an increased prevalence risk of depressive symptoms. Higher levels of SES may reduce the adverse effects of air pollution on depressive or anxiety symptoms.
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Poluição do Ar , Ansiedade , Depressão , População Rural , Humanos , Feminino , Estudos Transversais , Masculino , China/epidemiologia , Poluição do Ar/efeitos adversos , Poluição do Ar/estatística & dados numéricos , Depressão/epidemiologia , Depressão/psicologia , Adulto , População Rural/estatística & dados numéricos , Pessoa de Meia-Idade , Ansiedade/epidemiologia , Ansiedade/psicologia , Classe Social , Material Particulado/efeitos adversos , Prevalência , Ozônio/efeitos adversos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , IdosoRESUMO
Brevitaxin was prepared in nine steps from commercially available carnosic acid. The construction of the 1,4-benzodioxin moiety involved an unique stepwise ortho-quinone-engaged [4+2] cycloaddition. Two strategic stages were employed to prepare the highly unsaturated cycloaddition precursor 3: (1) synthesizing the diene moiety (C1-C2 and C10-C20 double bonds) by regioselective ortho-quinone tautomerization, and (2) installing four sp2-hybridized carbon atoms (C3, C5, C6 and C7) in one step using a SeO2-promoted chemo- and regioselective oxidation reaction.
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BACKGROUND: Although myotomy is crucial in peroral endoscopic myotomy (POEM) surgeries, its optimum length remains controversial. Herein, we propose a modified POEM with new method of tailoring myotomy length aim to evaluate the safety, efficacy, and clinical outcomes of this modified POEM compared with standard POEM in type I or II achalasia. METHODS: Seventy-five patients with type I or II achalasia who underwent POEM at the First Hospital of Jilin University between January 2018 and December 2022 were retrospectively analyzed. According to the myotomy approach, these patients were divided into the retrograde on-demand myotomy (RDM, n = 34), with myotomy beginning on gastric side and length tailored by determining the degree of lower esophageal sphincter (LES) distention, and standard myotomy (SM, n = 41) groups. The baseline data, myotomy length, operation time, clinical success rate, adverse event rate, and reflux-related adverse events were compared and analyzed. RESULTS: The median myotomy length in the RDM group was significantly shorter than that in the SM group (6 vs. 8 cm, respectively; p < 0.001). Moreover, the median myotomy time in the RDM group was significantly shorter than that in the SM group (10 vs. 16 min, respectively; p < 0.001). POEM was successfully performed in all the patients. At the 2-year follow-up, high clinical success rates were observed in both the RDM and SM groups (92.0% vs. 93.3%, respectively; p = 1.000). The incidence of intraoperative adverse events and postoperative reflux-related adverse events was low and comparable in both groups. CONCLUSIONS: RDM POEM is a safe and effective method for patients with type I or II achalasia. Furthermore, it has a shorter myotomy length and operation time than standard POEM technique.
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Acalasia Esofágica , Miotomia , Cirurgia Endoscópica por Orifício Natural , Humanos , Acalasia Esofágica/cirurgia , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Miotomia/métodos , Cirurgia Endoscópica por Orifício Natural/métodos , Resultado do Tratamento , Duração da Cirurgia , Idoso , Esfíncter Esofágico Inferior/cirurgia , Esofagoscopia/métodosRESUMO
Glucose metabolic disorders, prevalent in numerous metabolic diseases, have become a pressing global public health concern. Artemisinin (ART) and its derivatives, including artesunate (ARTs) and artemether (ARTe), have shown potential as metabolic regulators. However, the specific effects of ART and its derivatives on glucose metabolism under varying nutritional conditions and the associated molecular mechanisms remain largely unexplored. In this study, we examined the impact of ART, ARTs, and ARTe on glucose homeostasis using a mouse model subjected to different dietary regimens. Our findings revealed that ART, ARTs, and ARTe increased blood glucose levels in mice on a normal-chow diet (ND) while mitigating glucose imbalances in high-fat diet (HFD) mice. Notably, treatment with ART, ARTs, and ARTe had contrasting effects on in vivo insulin signaling, impairing it in ND mice and enhancing it in HFD mice. Moreover, the composition of gut microbiota underwent significant alterations following administration of ART and its derivatives. In ND mice, these treatments reduced the populations of bacteria beneficial for improving glucose homeostasis, including Parasutterella, Alloprevotella, Bifidobacterium, Ileibacterium, and Alistipes. In HFD mice, there was an increase in the abundance of beneficial bacteria (Alistipes, Akkermanisia) and a decrease in bacteria known to negatively impact glucose metabolism (Coprobacillus, Helicobacter, Mucispirillum, Enterorhabdus). Altogether, ART, ARTs, and ARTe exhibited distinct effects on the regulation of glucose metabolism, depending on the nutritional context, and these effects were closely associated with modifications in gut microbiota composition.
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Artemisininas , Dieta Hiperlipídica , Microbioma Gastrointestinal , Homeostase , Camundongos Endogâmicos C57BL , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Artemisininas/farmacologia , Masculino , Dieta Hiperlipídica/efeitos adversos , Camundongos , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Glucose/metabolismo , Artesunato/farmacologia , Artemeter/farmacologiaRESUMO
Bamboo cultivation, particularly Moso bamboo (Phyllostachys edulis), holds significant economic importance in various regions worldwide. Bamboo shoot degradation (BSD) severely affects productivity and economic viability. However, despite its agricultural consequences, the molecular mechanisms underlying BSD remain unclear. Consequently, we explored the dynamic changes of BSD through anatomy, physiology and the transcriptome. Our findings reveal ruptured protoxylem cells, reduced cell wall thickness and the accumulation of sucrose and reactive oxygen species (ROS) during BSD. Transcriptomic analysis underscored the importance of genes related to plant hormone signal transduction, sugar metabolism and ROS homoeostasis in this process. Furthermore, BSD appears to be driven by the coexpression regulatory network of senescence-associated gene transcription factors (SAG-TFs), specifically PeSAG39, PeWRKY22 and PeWRKY75, primarily located in the protoxylem of vascular bundles. Yeast one-hybrid and dual-luciferase assays demonstrated that PeWRKY22 and PeWRKY75 activate PeSAG39 expression by binding to its promoter. This study advanced our understanding of the molecular regulatory mechanisms governing BSD, offering a valuable reference for enhancing Moso bamboo forest productivity.
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Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Proteínas de Plantas , Brotos de Planta , Fatores de Transcrição , Brotos de Planta/metabolismo , Brotos de Planta/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Poaceae/genética , Poaceae/fisiologia , Poaceae/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Senescência Vegetal/genética , Transcriptoma , Parede Celular/metabolismoRESUMO
Objective: To quantitatively assess the impact of COVID-19 pandemic on public health, as well as its economic and social consequences in major economies, which is an international public health concern. The objective is to provide a scientific basis for policy interventions. Subject and methods: This study utilizes a multi-country, multi-sector CGE-COVID-19 model to analyze the repercussions of the pandemic in 2022. The re-search focuses on quantifying the effects of COVID-19 on the macroeconomy and various industry sectors within six economies: the United States, China, the EU, the United Kingdom, Japan, and South Korea. Results: The COVID-19 pandemic shock had the most significant impact on China and the EU, followed by notable effects observed in the United States and the United Kingdom. In contrast, South Korea and Japan experienced relatively minimal effects. The reduction in output caused by the pandemic has affected major economies in multiple sectors, including real industries such as forestry and fisheries, and the services such as hotels and restaurants. Conclusion: The overall negative macroeconomic impact of the epidemic on major economies has been significant. Strategic interventions encompassing initiatives like augmenting capital supply, diminishing corporate taxes and fees, offering individual subsidies, and nurturing international cooperation held the potential to mitigate the detrimental economic consequences and enhance the global-economic amid the pan-demic. Consequently, this study contributes to the advancement of global anti-epidemic policies targeting economic recovery. Moreover, using the CGE-COVID-19 model has enriched the exploration of general equilibrium models in PHEIC events.
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COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , China , Pesqueiros , IndústriasRESUMO
Sjogren's syndrome (SS) is an autoimmune disease characterized by dysfunction of exocrine glands, such as salivary glands. However, the molecular mechanism of salivary secretion dysfunction in SS is still unclear. Given the significance of glutathione peroxidase 4 (GPX4) in cellular redox homeostasis, we hypothesized that dysregulation of GPX4 may play a pivotal role in the pathogenesis of salivary secretion dysfunction observed in SS. The salivary gland of SS patients and the SS mouse model exhibited reduced expression of the ferroptosis inhibitor GPX4 and the important protein aquaporin 5 (AQP5), which is involved in salivary secretion. GPX4 overexpression upregulated and GPX4 knockdown downregulated AQP5 expression in salivary gland epithelial cells (SGECs) and salivary secretion. Bioinformatics analysis of GSE databases from SS patients' salivary glands revealed STAT4 as a key intermediary regulator between GPX4 and AQP5. A higher level of nuclear pSTAT4 was observed in the salivary gland of the SS mouse model. GPX4 overexpression inhibited and GPX4 knockdown promoted STAT4 phosphorylation and nuclear translocation in SGECs. CHIP assay confirmed the binding of pSTAT4 within the promoter of AQP5 inhibiting AQP5 transcription. GPX4 downregulation accumulates intracellular lipid ROS in SGECs. Lipid ROS inhibitor ferrostatin-1 treatment during in vitro and in vivo studies confirmed that lipid ROS activates STAT4 phosphorylation and nuclear translocation in SGECs. In summary, the downregulated GPX4 in SGECs contributes to salivary secretion dysfunction in SS via the lipid ROS/pSTAT4/AQP5 axis. This study unraveled novel targets to revitalize the salivary secretion function in SS patients.
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Aquaporina 5 , Células Epiteliais , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Espécies Reativas de Oxigênio , Fator de Transcrição STAT4 , Glândulas Salivares , Síndrome de Sjogren , Síndrome de Sjogren/metabolismo , Síndrome de Sjogren/genética , Síndrome de Sjogren/patologia , Animais , Humanos , Camundongos , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia , Aquaporina 5/metabolismo , Aquaporina 5/genética , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT4/metabolismo , Fator de Transcrição STAT4/genética , Modelos Animais de Doenças , Feminino , Regulação para Baixo , Masculino , Transdução de Sinais , Regulação da Expressão Gênica , Ferroptose/genética , Saliva/metabolismo , Pessoa de Meia-IdadeRESUMO
The inflammatory response is a key factor affecting tissue regeneration. Inspired by the immunomodulatory role of spermidine, an injectable double network hydrogel functionalized with spermidine (DN-SPD) is developed, where the first and second networks are formed by dynamic imine bonds and non-dynamic photo-crosslinked bonds respectively. The single network hydrogel before photo-crosslinking exhibits excellent injectability and thus can be printed and photo-crosslinked in situ to form double network hydrogels. DN-SPD hydrogel has demonstrated desirable mechanical properties and tissue adhesion. More importantly, an "operando" comparison of hydrogels loaded with spermidine or diethylenetriamine (DETA), a sham molecule resembling spermidine, has shown similar physical properties, but quite different biological functions. Specifically, the outcomes of 3 sets of in vivo animal experiments demonstrate that DN-SPD hydrogel can not only reduce inflammation caused by implanted exogenous biomaterials and reactive oxygen species but also promote the polarization of macrophages toward regenerative M2 phenotype, in comparison with DN-DETA hydrogel. Moreover, the immunoregulation by spermidine can also translate into faster and more natural healing of both acute wounds and diabetic wounds. Hence, the local administration of spermidine affords a simple but elegant approach to attenuate foreign body reactions induced by exogenous biomaterials to treat chronic refractory wounds.
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Diabetes Mellitus Experimental , Modelos Animais de Doenças , Hidrogéis , Inflamação , Espermidina , Cicatrização , Espermidina/farmacologia , Animais , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Inflamação/tratamento farmacológico , Camundongos , Masculino , Materiais BiocompatíveisRESUMO
Fatty acid desaturases (FADs) play pivotal roles in determining plant stress tolerance. Barley is the most salt-tolerant cereal crop. In this study, we performed genome-wide identification and characterization analysis of the FAD gene family in barley (Hordeum vulgare). A total of 24 HvFADs were identified and divided into four subfamilies based on their amino acid sequence similarity. HvFADs unevenly distributed on six of seven barley chromosomes, and three clusters of HvFADs mainly occurred on the chromosome 2, 3 and 6. Segmental duplication events were found to be a main cause for the HvFAD gene family expansion. The same HvFAD subfamily showed the relatively consistent exon-intron composition and conserved motifs of HvFADs. Cis-element analysis in HvFAD promoters indicated that the expression of HvFADs may be subject to complex regulation, especially stress-responsive elements that may involve in saline-alkaline stress response. Combined transcriptomic data with quantitative experiments, at least five HvFADs highly expressed in roots under salt or alkali treatment, suggesting they may participate in saline or alkaline tolerance in barley. This study provides novel and valuable insights for underlying salt/alkali-tolerant mechanisms in barley.
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Hordeum , Humanos , Hordeum/genética , Álcalis , Sequência de Aminoácidos , Cromossomos Humanos Par 2 , Grão Comestível , Solução SalinaRESUMO
OBJECTIVE: Our purpose is to unveil Andrographolide's potential multi-target and multi-mechanism therapeutic effects in treating OA via systematic network pharmacological analysis and cell experimental validation. MATERIALS AND METHODS: Initially, we gathered data from Andrographolide and OA-related databases to obtain information on Andrographolide's biological properties and the targets linked with OA. We developed a bioinformatic network about Andrographolide and OA, whereby we analyzed the network to identify potential therapeutic targets and mechanisms of action of Andrographolide. Subsequently, we used molecular docking to analyze the binding sites of Andrographolide to the target proteins. At the same time, SDF-1 was used to construct an OA cell model to verify the therapeutic effect of Andrographolide on OA and its effect on target proteins. RESULTS: Our experimental results show that Andrographolide has excellent pharmaceutical properties, by Lipinski's rules for drugs, suggesting that this compound can be considered to have a high therapeutic potential in drug development. 233 targets were preliminarily investigated, the mechanisms through which Andrographolide targets OA primarily involve the TNF signaling pathway, PI3K-AKT signaling pathway, IL-17 signaling pathway, and TLR signaling pathway. These mechanisms target OA by influencing immune and inflammatory responses in the joints, regulating apoptosis to prevent chondrocyte death. Finally, TNF-α, STAT3, TP53, IL-6, JUN, IL-1ß, HIF-1α, TGF-ß1, and AKT1 were identified as 9 key targets of Andrographolide anti-OA. In addition, our molecular docking analyzes with cell experimental validation further confirm the network pharmacology results. According to our molecular docking results, Andrographolide can bind to all the hub target proteins and has a good binding ability (binding energy < -5 kcal/mol), with the strongest binding affinity to AKT1 of -9.2 kcal/ mol. The results of cell experiments showed that Andrographolide treatment significantly increased the cell viability and the expression of COL2A1 and ACAN proteins. Moreover, 30 µM Andrographolide significantly reversed SDF-1-induced increases in the protein expression of TNF-α, STAT3, TP53, IL-6, JUN, IL-1ß, HIF-1α, and TGF-ß1, and decreases in the protein expression of AKT1. CONCLUSION: This study provides a comprehensive understanding of the potential therapeutic targets and mechanisms of action of Andrographolide in OA treatment. Our findings suggest that Andrographolide is a promising candidate for drug development in the management of OA.
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Diterpenos , Medicamentos de Ervas Chinesas , Fator de Crescimento Transformador beta1 , Interleucina-6 , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Fator de Necrose Tumoral alfaRESUMO
Nitrogen (N) fertilization is crucial for maintaining plant productivity. Clonal plants can share resources between connected ramets through clonal integration influencing microbial communities and regulating soil biogeochemical cycling, especially in the rhizosphere. However, the effect of various N fertilization practices on microbial communities in the rhizosphere of clonal ramets remain unknown. In this study, clonal fragments of Moso bamboo (Phyllostachys edulis), consisting of a parent ramet, an offspring ramet, and an interconnecting rhizome, were established in the field. NH4NO3 solution was applied to the parent, offspring ramets or rhizomes to investigate the effect of fertilization practices on the structure and function of rhizosphere microbial communities. The differences in N availability, microbial biomass and community composition, and abundance of nitrifying genes among rhizosphere soils of ramets gradually decreased during the rapid growth of Moso bamboo, irrespective of fertilization practice. The soil N availability variation, particularly in NO3-, caused by fertilization practices altered the rhizosphere microbial community. Soil N availability and stable microbial biomass N in parent fertilization were the highest, being 9.0 % and 18.7 %, as well as 60.8 % and 90.4 % higher than rhizome and offspring fertilizations, respectively. The microbial network nodes and links in rhizome fertilization were 1.8 and 7.5 times higher than in parent and offspring fertilization, respectively. However, the diversity of bacterial community and abundance of nitrifying and denitrifying genes were the highest in offspring fertilization among three practices, which may be associated with increased N loss. Collectively, the rhizosphere microbial community characteristics depended on fertilization practices by altering the clonal integration of N in Moso bamboo. Parent and rhizome fertilization were favorable for N retention in plant-soil system and resulted in more stable microbial functions than offspring fertilization. Our findings provide new insights into precision fertilization for the sustainable Moso bamboo forest management.
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Microbiota , Nitrogênio , Rizoma , Poaceae , Microbiologia do Solo , Solo , FertilizaçãoRESUMO
BACKGROUND: Sjögren's syndrome (SS) is a chronic autoimmune disease that predominantly affects exocrine glands. Previous studies have demonstrated that upregulated interferon-gamma (IFN-γ) in SS triggers ferroptosis in salivary gland epithelial cells (SGECs), resulting in impaired salivary gland secretion. However, the immune cells responsible for secreting IFN-γ remain unclear. Therefore, this study conducted bioinformatics analysis and molecular validation to identify the origin of IFN-γ in SS salivary gland. METHODS: The 'limma' package in R software was utilized to identify differentially expressed genes (DEGs) in the human SS dataset. Subsequently, the identified DEGs were compared with the ferroptosis database and screened through Cytoscape to determine candidate genes. The cellular localization and expression patterns of candidate genes were further confirmed in the salivary gland single-cell RNA sequence (scRNA-seq) data set from healthy control and SS mice. Furthermore, in vitro and in vivo studies were performed to analyze the effect of CD4 T-secreted IFN-γ on SGECs' ferroptosis and functions. RESULTS: Upregulated TLR4, IFNG, and IL33 were screened as candidates ferroptosis ferroptosis-inducing genes in SS salivary glands. The association of IFNG and IL33 with CD4 T cells was established through immune infiltration analysis. The expression of IFN-γ on CD4 T cells was robustly higher compared with that of IL33 as evidenced by scRNA-seq and immunofluorescence co-localization. Subsequent experiments conducted on candidate genes consistently demonstrated the potent ability of IFN-γ to induce SGECs' ferroptosis and inhibit AQP5 expression. CONCLUSIONS: Our findings indicate that CD4 T cell-secreted IFN-γ in SS induces SGECs' ferroptosis and inhibits AQP5 expression.
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Ferroptose , Síndrome de Sjogren , Humanos , Animais , Camundongos , Interferon gama/metabolismo , Linfócitos T CD4-Positivos , Interleucina-33/metabolismo , Glândulas Salivares , Células Epiteliais/metabolismoRESUMO
In comparison to traditional antioxidant treatment methods, the use of hydrogen to eliminate reactive oxygen species from the body has the advantages of high biological safety, strong selectivity, and high clearance rate. As an energy storage material, metal hydrides have been extensively studied and used in transporting hydrogen as clean energy, which can achieve a high hydrogen load and controlled hydrogen release. Considering the antioxidant properties of hydrogen and the delivery ability of metal hydrides, metal-hydride-based disease treatment strategies have attracted widespread attention. Up to now, metal hydrides have been reported for the treatment of tumors and a range of inflammation-related diseases. However, limited by the insufficient investment, the use of metal hydrides in disease treatment still has many shortcomings, such as low targeting efficiency, limited therapeutic activity, and complex material preparation process. Particularly, metal hydrides have been found to have a series of optical, acoustic, and catalytic properties when scaled up to the nanoscale, and these properties are also widely used to promote disease treatment effects. From this new perspective, we comprehensively summarize the very recent research progress on metal-hydride-based disease treatment in this review. Ultimately, the challenges and prospects of such a burgeoning cancer theranostics modality are outlooked to provide inspiration for the further development and clinical translation of metal hydrides.