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1.
Sci Total Environ ; 932: 173013, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38719041

RESUMO

As a highly effective broad-spectrum antibacterial agent, triclosan (TCS) is widely used in personal care and medical disinfection products, resulting in its widespread occurrence in aquatic and terrestrial environments, and even in the human body. Notably, the use of TCS surged during the COVID-19 outbreak, leading to increasing environmental TCS pollution pressure. From the perspective of environmental health, it is essential to systematically understand the environmental occurrence and behavior of TCS, its toxicological effects on biota and humans, and technologies to remove TCS from the environment. This review comprehensively summarizes the current knowledge regarding the sources and behavior of TCS in surface water, groundwater, and soil systems, focusing on its toxicological effects on aquatic and terrestrial organisms. Effluent from wastewater treatment plants is the primary source of TCS in aquatic systems, whereas sewage application and/or wastewater irrigation are the major sources of TCS in soil. Human exposure pathways to TCS and associated adverse outcomes were also analyzed. Skin and oral mucosal absorption, and dietary intake are important TCS exposure pathways. Reducing or completely degrading TCS in the environment is important for alleviating environmental pollution and protecting public health. Therefore, this paper reviews the removal mechanisms, including adsorption, biotic and abiotic redox reactions, and the influencing factors. In addition, the advantages and disadvantages of the different techniques are compared, and development prospects are proposed. These findings provide a basis for the management and risk assessment of TCS and are beneficial for the application of treatment technology in TCS removal.

2.
BMJ Open ; 14(5): e079167, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724047

RESUMO

INTRODUCTION: The 2020 American Heart Association guidelines encourage lay rescuers to provide chest compression-only cardiopulmonary resuscitation to simplify the process and encourage cardiopulmonary resuscitation initiation. However, recent clinical trials had contradictory results about chest compression-only cardiopulmonary resuscitation. This study will aim to compare standard and chest compressions-only cardiopulmonary resuscitation after out-of-hospital cardiac arrest. METHODS AND ANALYSIS: This study will retrieve only randomised and quasi-randomised controlled trials from the Cochrane Library, PubMed, Web of Science and Embase databases. Data on study design, participant characteristics, intervention details and outcomes will be extracted by a unified standard form. Primary outcomes to be assessed are hospital admission, discharge, and 30-day survival, and return of spontaneous circulation. The Grading of Recommendations, Assessment, Development and Evaluation framework will evaluate the quality of evidence. Cochrane's tool for assessing the risk of bias will evaluate risk deviation. If the I2 statistic is lower than 40%, the fixed-effects model will be used for meta-analysis. Otherwise, the random-effects model will be used. The search will be performed following the publication of this protocol (estimated to occur on 30 December 2024). DISCUSSION: This study will evaluate the effect of chest compression-only cardiopulmonary resuscitation after out-of-hospital cardiac arrest and provide evidence for cardiopulmonary resuscitation guidelines. ETHICS AND DISSEMINATION: No patient or public entity will be involved in this study. Therefore, the study does not need to be ethically reviewed. The results of the study will be disseminated through peer-reviewed journal publications and committee conferences. PROSPERO REGISTRATION NUMBER: CRD42021295507.


Assuntos
Reanimação Cardiopulmonar , Metanálise como Assunto , Parada Cardíaca Extra-Hospitalar , Revisões Sistemáticas como Assunto , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/mortalidade , Humanos , Reanimação Cardiopulmonar/métodos , Projetos de Pesquisa , Ensaios Clínicos Controlados Aleatórios como Assunto , Massagem Cardíaca/métodos , Massagem Cardíaca/normas
3.
EFSA J ; 22(5): e8779, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38741669

RESUMO

The food enzyme with two declared activities, bacillolysin (EC 3.4.24.28) and subtilisin (EC 3.4.21.62), is produced with the non-genetically modified Bacillus amyloliquefaciens strain AR-383 by AB Enzymes GmbH. The food enzyme is intended to be used in nine food manufacturing processes. Since residual amounts of total organic solids (TOS) are removed in the production of distilled alcohol, dietary exposure was calculated only for the remaining eight food manufacturing processes. Exposure was estimated to be up to 1.958 mg TOS/kg body weight per day in European populations. As the production strain qualifies for the qualified presumption of safety approach to safety assessment and no issues of concern arising from the production process of the food enzyme were identified, the Panel considered that no toxicological studies other than the assessment of allergenicity were necessary. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made, and 30 matches were found, including one food allergen (melon). The Panel considered that, under the intended conditions of use, the risk of allergic reactions by dietary exposure to this food enzyme cannot be excluded, but for individuals sensitised to melon, this would not exceed the risk of consuming melon. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

5.
Biomol Biomed ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38733633

RESUMO

Patients older than the expected age of the local population generally have limited life expectancy. The optimal treatment approach for very elderly patients with head and neck cancer remains uncertain. This study retrospectively analyzed patients over 78 years old, the expected age in 2019 for Chinese individuals, who underwent treatment for head and neck cancer at a tertiary cancer center in China. The study compared the overall survival rates among different treatment groups. The findings revealed that among patients eligible for surgery, radical resection yielded better outcomes compared to radiotherapy-based treatments, with a hazard ratio of 0.362 (95% CI 0.160-0.819, P = 0.015). Among patients who received radiotherapy, those who received a total dose exceeding 60 Gy had a significantly longer survival compared to those who received palliative doses, with median survival time of 31 months versus 14 months (P = 0.003). Among 78 patients who underwent conventional fractionated radiotherapy (CFRT), 15 patients (19.23%) experienced unscheduled treatment breaks with a median duration of 12 days. However, these treatment breaks did not appear to impact survival (P > 0.1). The study also suggested that altered fractionated radiotherapy, including hypofractionated radiotherapy (hypo-RT), could be a viable alternative to CFRT, offering similar survival outcomes with reduced treatment duration. In conclusion, eligible patients should be treated with curative intent, even if they are older than the expected age of the local population. When radiotherapy is indicated, altered fractionation, particularly hypo-RT, may be a favorable option to consider.

7.
J Cancer ; 15(10): 2900-2912, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706900

RESUMO

Background: Gastric cancer (GC) is a common malignancy with early detection being crucial for survival. Liquid biopsy analysis using cell-free nucleic acid is a preferred method for detection. Hence, we conducted a systematic review to assess the diagnostic efficacy of cell-free nucleic acid markers for GC. Methods: We searched PubMed and ISI Web of Science databases for articles that conformed to our inclusion and exclusion criteria from 2012 to 2022. The following information was abstracted: first author, year of publication, country/region, age, male proportion, tumor stage for cases, specimen type, measurement method, targeted markers and diagnostic related indicators (including sensitivity, specificity, AUC, P-value). Results: Fifty-eight studies examined cell-free RNAs (cfRNAs) with a total of 62 individual circulating markers and 7 panels in serum or plasma, while 21 studies evaluated cell-free DNAs (cfDNAs) with 29 individual circulating markers and 7 panels. For individual cfRNAs, the median (range) sensitivity and specificity were 80% (21% - 98%) and 80% (54% - 99%), respectively. The median (range) sensitivity and specificity for cfRNA panels were 86% (83% - 90%) and 75% (60% - 98%), respectively. In comparison, the median (range) sensitivity and specificity reported for individual cfDNAs were 50% (18% - 96%) and 93% (57% - 100%), respectively, while cfDNA panels had a median (range) sensitivity and specificity of 85% (41% - 92%) and 73.5% (38% - 90%), respectively. The meta results indicate that cfRNA markers exhibit high sensitivity (80%) and low specificity (80%) for detecting GC, while cfDNA markers have lower sensitivity (59%) but higher specificity (92%). Conclusions: This review has demonstrated that cell-free nucleic acids have the potential to serve as useful diagnostic markers for GC. Given that both cfRNA and cfDNA markers have shown promising diagnostic performance for GC, the combination of the two may potentially enhance diagnostic efficiency.

8.
Heliyon ; 10(9): e29688, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707301

RESUMO

Accurate assessment of evapotranspiration (ETa) and crop coefficient (Kc) is crucial for optimizing irrigation practices in water-scarce regions. While satellite-based surface energy balance models offer a promising solution, their application to sparse canopies like apple orchards requires specific validation. This study investigated the spatial and temporal dynamics of ETa and Kc in a drip-irrigated 'Pink Lady' apple orchard under Mediterranean conditions over three growing seasons (2012/13, 2013/14, 2014/15). The METRIC model, incorporating calibrated sub-models for leaf area index (LAI), surface roughness (Zom), and soil heat flux (G), was employed to estimate ETa and Kc. These estimates were validated against field-scale Eddy Covariance data. Results indicated that METRIC overpredicted Kc and ETa with errors less than 10 %. These findings highlight the potential of the calibrated METRIC model as a valuable decision-making tool for irrigation management in apple orchards.

9.
Front Bioeng Biotechnol ; 12: 1390337, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707496

RESUMO

Objective: This study aims to develop and evaluate the biocompatibility and osteogenic potential of a novel injectable strontium-doped hydroxyapatite bone-repair material. Methods: The properties of strontium-doped hydroxyapatite/chitosan (Sr-HA/CS), hydroxyapatite/chitosan (HA/CS) and calcium phosphate/chitosan (CAP/CS) were assessed following their preparation via physical cross-linking and a one-step simplified method. Petri dishes containing Escherichia coli and Staphylococcus epidermidis were inoculated with the material for in vitro investigations. The material was also co-cultured with stem cells derived from human exfoliated deciduous teeth (SHEDs), to assess the morphology and proliferation capability of the SHEDs, Calcein-AM staining and the Cell Counting Kit-8 assay were employed. Osteogenic differentiation of SHEDs was determined using alkaline phosphatase (ALP) staining and Alizarin Red staining. For in vivo studies, Sr-HA/CS was implanted into the muscle pouch of mice and in a rat model of ovariectomy-induced femoral defects. Hematoxylin-eosin (HE) staining was performed to determine the extent of bone formation and defect healing. The formation of new bone was determined using Masson's trichrome staining. The osteogenic mechanism of the material was investigated using Tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemical studies. Results: X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS) showed that strontium was successfully doped into HA. The Sr-HA/CS material can be uniformly squeezed using a syringe with a 13% swelling rate. Sr-HA/CS had a significant antibacterial effect against both E. coli and S. epidermidis (p < 0.05), with a stronger effect observed against E. coli. The Sr-HA/CS significantly improved cell proliferation and cell viability in vitro studies (p < 0.05). Compared to CAP/CS and CS, Sr-HA/CS generated a substantially greater new bone area during osteoinduction experiments (p < 0.05, p < 0.001). The Sr-HA/CS material demonstrated a significantly higher rate of bone repair in the bone defeat studies compared to the CAP/CS and CS materials (p < 0.01). The OCN-positive area and TRAP-positive cells in Sr-HA/CS were greater than those in control groups (p < 0.05). Conclusion: A novel injectable strontium-doped HA bone-repair material with good antibacterial properties, biocompatibility, and osteoinductivity was successfully prepared.

10.
Ecotoxicol Environ Saf ; 278: 116444, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38728943

RESUMO

Silicosis is a disease characterized by lung inflammation and fibrosis caused by long-term inhalation of free silicon dioxide (SiO2). Recent studies have found that a large number of lymphatic hyperplasia occurs during the occurrence and development of silicosis. miRNAs play an important role in lymphangiogenesis. However, the regulation and mechanism of miRNAs on lymphangiogenesis in silicosis remain unclear. In this study, lymphangiogenesis was observed in silicosis rats, and VEGF-C-targeted miRNAs were screened, and the effect of miRNAs on the formation of human lymphatic endothelial cells (HLECs) tubular structure was investigated in vitro. The results showed that SiO2 promoted the expressions of Collagen Ι and α-SMA, TNF-α, IL-6 and VEGF-C increased first and then decreased, and promoted the formation of lymphatic vessels. Bioinformatics methods screened miR-455-3p for targeted binding to VEGF-C, and dual luciferase reporter genes confirmed VEGF-C as the target gene of miR-455-3p, and miR-455-3p was down-regulated in the lung tissue of silicosis rats. Transfection of miR-455-3p Inhibitors down-regulated the expression level of miR-455-3p and up-regulated the expression levels of VEGF-C and VEGFR-3 in HLECs, enhanced migration ability and increased tube formation. Transfection of miR-455-3p Mimics showed an opposite trend. These results suggest that miR-455-3p further regulates the tubular structure formation of HLECs by regulating VEGF-C/VEGFR3. Therefore, targeting miR-455-3p may provide a new therapeutic strategy for SiO2-induced silicosis injury.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38691150

RESUMO

Urinary tract infection (UTI) is one of the most prevalent bacterial infectious diseases worldwide. However, the resistance of urinary pathogens to other UTI antibiotics such as trimethoprim and trimethoprim/sulphamethoxazole increased. Pivmecillinam is a prodrug of mecillinam, which is effective for the treatment of urinary tract infections. The purpose of this study was to assess the safety, and pharmacokinetics of pivmecillinam and mecillinam after single- and multiple-dose oral administration of pivmecillinam tablets in healthy Chinese subjects. The study also investigated the profile of urinary excretion of mecillinam, as well as the effect of food and gender on the pharmacokinetics of pivmecillinam and mecillinam. This study was a single-center, open-label phase I study carried out in three groups. In total, 34 subjects were included in the study: group 1-food effect study with pivmecillinam 200 mg (n = 12); group 2-single- and multiple-dose study with pivmecillinam 400 mg (n = 12); group 3-single dose study with pivmecillinam 600 mg (n = 10). The plasma and urine concentrations of pivmecillinam and mecillinam were measured, and their pharmacokinetics were calculated. Treatment-emergent adverse events were evaluated and recorded in safety assessments for three groups. No severe adverse events were found in this study. After a single dose of pivmecillinam was taken orally, the maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) of pivmecillinam increased in a dose-proportional manner, nor did mecillinam. Food had significant effects on Cmax and AUC0-t of pivmecillinam and Cmax of mecillinam. The mean cumulative percentage of urine excretion of mecillinam at 0 to 24 h ranged from 35.5 to 44.0%. Urinary cumulative excretion is relative to the drug dose, but the diet and multiple-dose administration did not affect the urinary cumulative excretion rate. The safety and pharmacokinetics of pivmecillinam and mecillinam after single- (200/400/600 mg) or multiple-dose (400 mg) administration were demonstrated in healthy Chinese subjects. Food affected the pharmacokinetics of pivmecillinam and mecillinam.

12.
bioRxiv ; 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38746303

RESUMO

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), omega-3 polyunsaturated fatty acids (ω-3 PUFAs) derived from fish oil, are widely used as dietary supplements and FDA-approved treatments for hypertriglyceridemia. However, studies investigating the effects of EPA and DHA on colorectal carcinogenesis (CRC) have yielded conflicting results. The factors that determine these discrepant results remain unknown. Resolvins, oxidative metabolites of EPA and DHA, inhibit key pro-tumorigenic cytokine and chemokine signaling of colorectal cancer (e.g., IL-6, IL-1ß, and CCL2). 15-lipoxygenase-1 (ALOX15), a critical enzyme for resolvin generation is commonly lost during human CRC. Whether ALOX15 expression, as a host factor, modulates the effects of EPA and DHA on CRC remains unknown. Therefore, we evaluated the effects of ALOX15 transgenic expression in colonic epithelial cells on resolvin generation by EPA and DHA and CRC in mouse models representative of human CRC. Our results revealed that 1) EPA and DHA effects on CRC were diverse, ranging from suppressive to promotive, and these effects were occasionally altered by the formulations of EPA and DHA (free fatty acid, ethyl ester, triglyceride); 2) EPA and DHA uniformly suppressed CRC in the presence of intestinal ALOX15 transgenic expression, which induced the production of resolvins, decreased colonic CCL3-5 and CXCL-5 expression and tumor associated macrophages while increasing CD8 T cell abundance in tumor microenvironment; and 3) RvD5, the predominant resolvin produced by ALOX15, inhibited macrophage generation of pro-tumorigenic cytokines. These findings demonstrate the significance of intestinal ALOX15 expression as a host factor in determining the effects of EPA and DHA on CRC. Significance: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are widely used as dietary supplements and FDA-approved treatments for hypertriglyceridemia. Studies of EPA and DHA effects on colorectal carcinogenesis (CRC) have revealed inconsistencies; factors determining the direction of their impact on CRC have remained unidentified. Our data show that EPA and DHA effects on CRC were divergent and occasionally influenced by their formulations. More importantly, intestinal 15-lipoxgenase-1 (ALOX15) expression modulated EPA and DHA effects on CRC, leading to their consistent suppression of CRC. ALOX15 promoted EPA and DHA oxidative metabolism to generate resolvins, which inhibited key pro-tumorigenic inflammatory cytokines and chemokines, including IL-6. IL-1ß, and CCL2. ALOX15 is therefore an important host factor in determining EPA and DHA effects on CRC.

13.
Small ; : e2401299, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38746996

RESUMO

The immunosuppressive tumor microenvironment (TME) reduces the chimeric antigen receptor (CAR) T-cell therapy against solid tumors. Here, a CAR T cell membrane-camouflaged nanocatalyst (ACSP@TCM) is prepared to augment CAR T cell therapy efficacy against solid tumors. ACSP@TCM is prepared by encapsulating core/shell Au/Cu2- xSe and 3-bromopyruvate with a CAR T cell membrane. It is demonstrated that the CAR T cell membrane camouflaging has much better-targeting effect than the homologous tumors cell membrane camouflaging. ACSP@TCM has an appealing synergistic chemodynamic/photothermal therapy (CDT/PTT) effect that can induce the immunogenic cell death (ICD) of NALM 6 cells. Moreover, 3-bromopyruvate can inhibit the efflux of lactic acid by inhibiting the glycolysis process, regulating the acidity of TME, and providing a more favorable environment for the survival of CAR T cells. In addition, the photoacoustic (PA) imaging and computed tomography (CT) imaging performance can guide the ACSP@TCM-mediated tumor therapy. The results demonstrated that the ACSP@TCM significantly enhanced the CAR T cell therapy efficacy against NALM 6 solid tumor mass, and completely eliminated tumors. This work provides an effective tumor strategy for CAR T cell therapy in solid tumors.

14.
Plant Cell Environ ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747645

RESUMO

Potassium (K) fertilisation has frequently been shown to enhance plant resistance against pathogens, though the mechanisms remain elusive. This study investigates the interaction dynamics between Nicotiana benthamiana and the pathogen Alternaria longipes under different planta K levels. On the host side, adding K activated the expressions of three NLR (nucleotide-binding domain and leucine-rich repeat-containing proteins) resistance genes, including NbRPM1, NbR1B23 and NbNBS12. Silencing these NLRs attenuated resistance in high-K (HK, 40.8 g/kg) plant, whereas their overexpression strengthened resistance in low-K (LK, 23.9 g/kg) plant. Typically, these NLRs mainly strengthened plant resistance via promoting the expression of pathogenesis-related genes (PRs), ROS burst and synthesis of antifungal metabolites in HK plant. On the pathogen side, the expression of effectors HKCSP1, HKCSP2 and LKCSP were shown to be related to planta K content. A. longipes mainly expressed effectors HKCSP1 and HKCSP2 in HK plant to interfere host resistance. HKCSP1 physically interacted with NbRPM1 to promote the degradation of NbRPM1, then attenuated related resistance in HK N. benthamiana. Meanwhile, HKCSP2 directly interacted with NbPR5 to suppress resistance in HK plant. In LK plant, A. longipes mainly deployed LKCSP that interacted with NbR1B23 to interfere reduce resistance in N. benthamiana. Overall, our research insights that both pathogen and host mobilise distinct strategies to outcompete each other during interactions in different K nutrient environments.

15.
ACS Sens ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747895

RESUMO

Quantitative nucleic acid amplification tests are of great importance for diagnostics, but current approaches require complex and costly optical setups that limit their nonlaboratory applications. Herein we describe the implementation of a microfluidics platform that can perform binary DNA-amplification-activated droplet sorting. The digital sort-enabled counting (DISCO) platform enables label-free absolute quantification of the nucleic acid. This is achieved by provoking a pH change in droplets through a loop-mediated isothermal amplification (LAMP) reaction, followed by using sorting by interfacial tension (SIFT) to direct positive and negative droplets to different outlets. With the use of on-chip electrodes at both outlets, we demonstrate that the digital electrical counting of target DNA and RNA can be realized. DISCO is a promising approach for realizing sensitive nucleic acid quantification in point-of-care settings.

16.
Mol Genet Genomics ; 299(1): 51, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743077

RESUMO

This study examines the prognostic role and immunological relevance of EMP1 (epithelial membrane protein-1) in a pan-cancer analysis, with a focus on ovarian cancer. Utilizing data from TCGA, CCLE, and GTEx databases, we assessed EMP1 mRNA expression and its correlation with tumor progression, prognosis, and immune microenvironment across various cancers. Our results indicate that EMP1 expression is significantly associated with poor prognosis in multiple cancer types, including ovarian, bladder, testicular, pancreatic, breast, brain, and uveal melanoma. Immune-related analyses reveal a positive correlation between EMP1 and immune cell infiltration, particularly neutrophils, macrophages, and dendritic cells, as well as high expression of immune checkpoint such as CD274, HAVCR2, IL10, PDCD1LG2, and TGFB1 in most tumors. In vivo experiments confirm that EMP1 promotes ovarian cancer cell proliferation, metastasis, and invasion. In conclusion, EMP1 emerges as a potential prognostic biomarker and therapeutic target in various cancers, particularly ovarian cancer, due to its influence on tumor progression and immune cell dynamics. Further research is warranted to elucidate the precise mechanisms of EMP1 in cancer biology and to translate these findings into clinical applications.


Assuntos
Biomarcadores Tumorais , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , Microambiente Tumoral , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Prognóstico , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Biomarcadores Tumorais/genética , Animais , Proliferação de Células/genética , Linhagem Celular Tumoral , Camundongos , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Glicoproteínas de Membrana/genética
17.
Acta Pharmacol Sin ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744938

RESUMO

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease with an unclear pathogenesis, and there is currently no approved drug for the treatment of this disease. Iguratimod, as a novel clinical anti-rheumatic drug in China and Japan, has shown remarkable efficacy in improving the symptoms of patients with pSS in clinical studies. In this study we investigated the mechanisms underlying the therapeutic effect of iguratimod in the treatment of pSS. Experimental Sjögren's syndrome (ESS) model was established in female mice by immunizing with salivary gland protein. After immunization, ESS mice were orally treated with iguratimod (10, 30, 100 mg·kg-1·d-1) or hydroxychloroquine (50 mg·kg-1·d-1) for 70 days. We showed that iguratimod administration dose-dependently increased saliva secretion, and ameliorated ESS development by predominantly inhibiting B cells activation and plasma cell differentiation. Iguratimod (30 and 100 mg·kg-1·d-1) was more effective than hydroxychloroquine (50 mg·kg-1·d-1). When the potential target of iguratimod was searched, we found that iguratimod bound to TEC kinase and promoted its degradation through the autophagy-lysosome pathway in BAFF-activated B cells, thereby directly inhibiting TEC-regulated B cells function, suggesting that the action mode of iguratimod on TEC was different from that of conventional kinase inhibitors. In addition, we found a crucial role of TEC overexpression in plasma cells of patients with pSS. Together, we demonstrate that iguratimod effectively ameliorates ESS via its unique suppression of TEC function, which will be helpful for its clinical application. Targeting TEC kinase, a new regulatory factor for B cells, may be a promising therapeutic option.

18.
J Am Chem Soc ; 146(19): 13296-13305, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38695301

RESUMO

The activation of esters by strong Lewis acids via the formation of covalent adducts is a classic strategy to give reactivity; however, this approach frequently incurs limited turnover due to the low efficiency in the dissociation of catalyst from a stable catalyst-product complex. While the use of some weak interaction catalysts that can easily dissociate from any bonding complexes in the reaction system would solve this catalyst turnover problem, the poor catalytic activity in the ester activation that can be provided by these noncovalent forces in turn sets up a formidable challenge. Herein, we describe the activation and catalytic transformation of esters by weak interactions, which provides a promising platform to reconcile the catalytic activity and turnover problems. Several tailored chalcogen-bonding catalysts were developed for the activation of esters, enabling achieving several inherently low reactive Diels-Alder reactions as well as the ring-opening polymerization of lactones through weak chalcogen bonding interactions. This supramolecular catalysis approach is particularly highlighted by its capability to promote some uncommon Diels-Alder reactions involving using dienes bearing electron-withdrawing groups coupled by α,ß-unsaturated ester as dienophiles and substrate incorporating competitive Lewis basic sites, in which typical strong Lewis acids showed low catalytic efficiency, while representative hydrogen and halogen bonding catalysts were inactive.

19.
J Agric Food Chem ; 72(19): 11278-11291, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38708781

RESUMO

Moringa seeds are an excellent dietary source of phytochemicals (i.e., glucosinolates, GSLs; isothiocyanates, ITCs) with health-beneficial effects. Although numerous studies have been conducted on moringa seeds, the effect of germination on the regulation of GSLs remains scarcely explored. The present study investigated the dynamic changes of GSLs in moringa seeds during germination (at 25, 30, and 35 °C for 6 days in the dark) through an untargeted metabolomics approach and compared the antioxidant capacity of ungerminated and germinated moringa seeds. Our results showed that germination significantly increased the total GSL content from 150 (day 0) to 323 µmol/g (35 °C, day 6) on a dry weight (DW) basis, especially glucomoringin (GMG), the unique glucosinolate in moringa seeds, which was significantly upregulated from 61 (day 0) to 149 µmol/g DW (35 °C, day 4). The upregulation of GMG corresponded to the metabolism of tyrosine, which might be the initial precursor for the formation of GMG. In addition, germination enhanced the total ITC content from 85 (day 0) to 239 µmol SE/g DW (35 °C, day 6), indicating that germination may have also increased the activity of myrosinase. Furthermore, germination remarkably increased the total phenolic content (109-507 mg GAE/100 g DW) and antioxidant capacity of moringa seeds. Our findings suggest that moringa sprouts could be promoted as a novel food and/or ingredient rich in GMG.


Assuntos
Germinação , Glucosinolatos , Moringa , Sementes , Tirosina , Sementes/química , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Tirosina/metabolismo , Tirosina/análise , Moringa/química , Moringa/metabolismo , Moringa/crescimento & desenvolvimento , Glucosinolatos/metabolismo , Glucosinolatos/análise , Glucosinolatos/química , Antioxidantes/metabolismo , Antioxidantes/química , Antioxidantes/análise
20.
ACS Nano ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717846

RESUMO

P3-layered transition oxide cathodes have garnered considerable attention owing to their high initial capacity, rapid Na+ kinetics, and less energy consumption during the synthesis process. Despite these merits, their practical application is hindered by the substantial capacity degradation resulting from unfavorable structural transformations, Mn dissolution and migration. In this study, we systematically investigated the failure mechanisms of P3 cathodes, encompassing Mn dissolution, migration, and the irreversible P3-O3' phase transition, culminating in severe structural collapse. To address these challenges, we proposed an interfacial spinel local interlocking strategy utilizing P3/spinel intergrowth oxide as a proof-of-concept material. As a result, P3/spinel intergrowth oxide cathodes demonstrated enhanced cycling performance. The effectiveness of suppressing Mn migration and maintaining local structure of interfacial spinel local interlocking strategy was validated through depth-etching X-ray photoelectron spectroscopy, X-ray absorption spectroscopy, and in situ synchrotron-based X-ray diffraction. This interfacial spinel local interlocking engineering strategy presents a promising avenue for the development of advanced cathode materials for sodium-ion batteries.

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