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1.
Nat Methods ; 19(2): 205-215, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35132245

RESUMO

Transgenic expression of bacterial nitroreductase (NTR) enzymes sensitizes eukaryotic cells to prodrugs such as metronidazole (MTZ), enabling selective cell-ablation paradigms that have expanded studies of cell function and regeneration in vertebrates. However, first-generation NTRs required confoundingly toxic prodrug treatments to achieve effective cell ablation, and some cell types have proven resistant. Here we used rational engineering and cross-species screening to develop an NTR variant, NTR 2.0, which exhibits ~100-fold improvement in MTZ-mediated cell-specific ablation efficacy, eliminating the need for near-toxic prodrug treatment regimens. NTR 2.0 therefore enables sustained cell-loss paradigms and ablation of previously resistant cell types. These properties permit enhanced interrogations of cell function, extended challenges to the regenerative capacities of discrete stem cell niches, and novel modeling of chronic degenerative diseases. Accordingly, we have created a series of bipartite transgenic reporter/effector resources to facilitate dissemination of NTR 2.0 to the research community.


Assuntos
Metronidazol/farmacologia , Nitrorredutases/metabolismo , Pró-Fármacos/química , Animais , Animais Geneticamente Modificados , Células CHO , Cricetulus , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Metronidazol/farmacocinética , Nitrorredutases/química , Nitrorredutases/genética , Pró-Fármacos/farmacologia , Engenharia de Proteínas/métodos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Retina/citologia , Retina/efeitos dos fármacos , Vibrio/enzimologia , Peixe-Zebra/genética
2.
Chem Soc Rev ; 53(10): 5149-5189, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38566609

RESUMO

The electrochemical reduction of CO2 into value-added chemicals has been explored as a promising solution to realize carbon neutrality and inhibit global warming. This involves utilizing the electrochemical CO2 reduction reaction (CO2RR) to produce a variety of single-carbon (C1) and multi-carbon (C2+) products. Additionally, the electrolyte solution in the CO2RR system can be enriched with nitrogen sources (such as NO3-, NO2-, N2, or NO) to enable the synthesis of organonitrogen compounds via C-N coupling reactions. However, the electrochemical conversion of CO2 into valuable chemicals still faces challenges in terms of low product yield, poor faradaic efficiency (FE), and unclear understanding of the reaction mechanism. This review summarizes the promising strategies aimed at achieving selective production of diverse carbon-containing products, including CO, formate, hydrocarbons, alcohols, and organonitrogen compounds. These approaches involve the rational design of electrocatalysts and the construction of coupled electrocatalytic reaction systems. Moreover, this review presents the underlying reaction mechanisms, identifies the existing challenges, and highlights the prospects of the electrosynthesis processes. The aim is to offer valuable insights and guidance for future research on the electrocatalytic conversion of CO2 into carbon-containing products of enhanced value-added potential.

3.
J Cell Mol Med ; 28(1): e18023, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38146147

RESUMO

In recent years, an increasing number of observational studies have revealed an association between gut microbiota composition and psoriasis patients. However, whether this association reflects a causal relationship remains unclear. This study aimed to identify the causal relationship between gut microbiota and psoriasis through relevant research. In order to determine whether gut microbiota and psoriasis are causally related, we conducted a Mendelian randomization analysis using summary statistics from genome-wide association studies (GWAS). As the exposure factor, we used summary statistics data from a GWAS study conducted by the MiBioGen Consortium, including 18,340 individuals with whole-genome gut microbiota composition, and data from the FinnGen GWAS study on psoriasis, including 9267 patients and 364,071 controls as the disease outcome. Two-sample Mendelian randomization analysis was subsequently performed with inverse variance weighted, MR-Egger and weighted median, while sensitivity analyses were conducted to address heterogeneity and horizontal pleiotropy. The IVW results confirmed the causal relationship between certain gut microbiota groups and psoriasis. Specifically, family Veillonellaceae (OR = 1.162, 95% CI: 1.038-1.301, p = 0.009), genus Candidatus Soleaferrea (OR = 1.123, 95% CI: 1.011-1.247, p = 0.030) and genus Eubacterium fissicatena group (OR = 0.831, 95% CI: 0.755-0.915, p = 0.00016) showed significant associations. Sensitivity analysis did not reveal any abnormalities in SNPs. Currently, we have found some causal relationship between the gut microbiota and psoriasis. However, the study needs further RCTs for further validation.


Assuntos
Microbioma Gastrointestinal , Psoríase , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único
4.
Expert Rev Mol Med ; 26: e10, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38659380

RESUMO

Autoimmune diseases are pathological autoimmune reactions in the body caused by various factors, which can lead to tissue damage and organ dysfunction. They can be divided into organ-specific and systemic autoimmune diseases. These diseases usually involve various body systems, including the blood, muscles, bones, joints and soft tissues. The transient receptor potential (TRP) and PIEZO receptors, which resulted in David Julius and Ardem Patapoutian winning the Nobel Prize in Physiology or Medicine in 2021, attracted people's attention. Most current studies on TRP and PIEZO receptors in autoimmune diseases have been carried out on animal model, only few clinical studies have been conducted. Therefore, this study aimed to review existing studies on TRP and PIEZO to understand the roles of these receptors in autoimmune diseases, which may help elucidate novel treatment strategies.


Assuntos
Doenças Autoimunes , Canais Iônicos , Canais de Potencial de Receptor Transitório , Humanos , Doenças Autoimunes/metabolismo , Doenças Autoimunes/imunologia , Animais , Canais Iônicos/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo
5.
Exp Eye Res ; 244: 109939, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38789021

RESUMO

Transforming growth factor-ß2 (TGF-ß2) induced fibrogenic changes in human trabecular meshwork (HTM) cells have been implicated in trabecular meshwork (TM) damage and intraocular pressure (IOP) elevation in primary open-angle glaucoma (POAG) patients. Silibinin (SIL) exhibited anti-fibrotic properties in various organs and tissues. This study aimed to assess the effects of SIL on the TGF-ß2-treated HTM cells and to elucidate the underlying mechanisms. Our study found that SIL effectively inhibited HTM cell proliferation, attenuated TGF-ß2-induced cell migration, and mitigated TGF-ß2-induced reorganization of both actin and vimentin filaments. Moreover, SIL suppressed the expressions of fibronectin (FN), collagen type I alpha 1 chain (COL1A1), and alpha-smooth muscle actin (α-SMA) in the TGF-ß2-treated HTM cells. RNA sequencing indicated that SIL interfered with the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway, extracellular matrix (ECM)-receptor interaction, and focal adhesion in the TGF-ß2-treated HTM cells. Western blotting demonstrated SIL inhibited the activation of Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and the downstream PI3K/AKT signaling pathways induced by TGF-ß2, potentially contributing to its inhibitory effects on ECM protein production in the TGF-ß2-treated HTM cells. Our study demonstrated the ability of SIL to inhibit TGF-ß2-induced fibrogenic changes in HTM cells. SIL could be a potential IOP-lowering agent by reducing the fibrotic changes in the TM tissue of POAG patients, which warrants further investigation through additional animal and clinical studies.


Assuntos
Movimento Celular , Proliferação de Células , Janus Quinase 2 , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Fator de Transcrição STAT3 , Transdução de Sinais , Silibina , Malha Trabecular , Fator de Crescimento Transformador beta2 , Humanos , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/metabolismo , Malha Trabecular/patologia , Fator de Crescimento Transformador beta2/farmacologia , Fator de Crescimento Transformador beta2/metabolismo , Fator de Transcrição STAT3/metabolismo , Janus Quinase 2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Cultivadas , Silibina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Western Blotting , Fibrose , Silimarina/farmacologia , Antioxidantes/farmacologia , Glaucoma de Ângulo Aberto/metabolismo , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/patologia
6.
Langmuir ; 40(12): 6550-6561, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38483322

RESUMO

With environmental pollution becoming more serious, developing efficient treatment technologies for all kinds of organic wastewater has become the focus of current research. In this work, the coaxial electrospinning technology was used to one-step fabricate a porous and underwater superoleophobic polyacrylonitrile nanofibrous membrane with an Fe-based metal-organic framework (MIL-100(Fe)). Benefiting from the synergistic effect of two jets, the nanofibers are smaller and denser, which prompt the exposure of more nanomaterial additives (MIL-100(Fe)). The BET surface area increased to 202.888 m2/g, and the membranes demonstrated outstanding underwater superoleophobicity. Moreover, compared with traditional blended matrix membranes by the single-axis method, separation of the modifier and membrane matrix material by coaxial methods also maintained excellent mechanical properties, which enhanced Young's modulus 3.4 times (∼1.34 MPa). As a result, facing soluble dyes, the porous C-PAN/MIL-100(Fe) membrane can demonstrate outstanding and fast adsorptive property (the Qm of MB and CR reached 44.71 and 88.74 mg g-1, respectively). For oily emulsion, the hydrophilic and oleophobic nanofibrous reticular surface provided excellent separation performance (flux: 1124.0-1549.3 L m-2 h-1, R > 98%). Moreover, the porous and underwater superoleophobic C-PAN/MIL-100(Fe)-0.5 membrane can synchronously purify the dye/oil mixture emulsions by one-step filtration. Based on the above performance, we believe that the modified nanofibrous membrane prepared by one-step coaxial electrospinning technology can promote more studies of the development of membrane preparation technology in the field of oily wastewater treatment.

7.
J Pediatr Gastroenterol Nutr ; 78(4): 817-826, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38451058

RESUMO

OBJECTIVES: Percutaneous electrical nerve field stimulation (PENFS) has demonstrated promise in single-center trials for pediatric abdominal pain-related disorders of gut-brain interaction (DGBI). Our aim was to explore efficacy of PENFS as standard therapy for DGBI in a registry involving multiple pediatric gastroenterology referral centers. METHODS: This was a multicenter, prospective open-label registry of children (8-18 years) undergoing PENFS for DGBI at seven tertiary care gastroenterology clinics. DGBI subtypes were classified by Rome IV criteria. Parents and patients completed Abdominal Pain Index (API), Nausea Severity Scale (NSS), and Functional Disability Inventory (FDI) questionnaires before, during therapy and at follow-up visits up to 1 year later. RESULTS: A total of 292 subjects were included. Majority (74%) were female with median (interquartile range [IQR]) age 16.3 (14.0, 17.7) years. Most (68%) met criteria for functional dyspepsia and 61% had failed ≥4 pharmacologic therapies. API, NSS, and FDI scores showed significant declines within 3 weeks of therapy, persisting long-term in a subset. Baseline (n = 288) median (IQR) child-reported API scores decreased from 2.68 (1.84, 3.58) to 1.99 (1.13, 3.27) at 3 weeks (p < 0.001) and 1.81 (0.85, 3.20) at 3 months (n = 75; p < 0.001). NSS scores similarly improved from baseline, persisting at three (n = 74; p < 0.001) and 6 months later (n = 55; p < 0.001). FDI scores displayed similar reductions at 3 months (n = 76; p = 0.01) but not beyond. Parent-reported scores were consistent with child reports. CONCLUSIONS: This large, comprehensive, multicenter registry highlights efficacy of PENFS for gastrointestinal symptoms and functionality for pediatric DGBI.


Assuntos
Encefalopatias , Dispepsia , Gastroenteropatias , Síndrome do Intestino Irritável , Humanos , Criança , Masculino , Feminino , Adolescente , Estudos Prospectivos , Gastroenteropatias/terapia , Gastroenteropatias/diagnóstico , Dor Abdominal/etiologia , Dor Abdominal/terapia , Dor Abdominal/diagnóstico , Dispepsia/diagnóstico , Inquéritos e Questionários , Acetaminofen , Encéfalo , Síndrome do Intestino Irritável/diagnóstico
8.
Pediatr Transplant ; 28(3): e14708, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38553812

RESUMO

BACKGROUND: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection. METHODS: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance. RESULTS: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection. CONCLUSION: The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.


Assuntos
Ácidos Nucleicos Livres , Transplante de Coração , Adulto , Humanos , Criança , Estudos Prospectivos , Biomarcadores , Rejeição de Enxerto , Doadores de Tecidos
9.
J Asthma ; : 1-9, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38913839

RESUMO

OBJECTIVES: Dexamethasone has become the standard of care for pediatric patients with status asthmaticus in the emergency department (ED) setting. Inpatient providers often must decide between continuing the second dose of dexamethasone or transitioning to prednisone. The effectiveness of receiving dexamethasone followed by prednisone (combination therapy) compared to only prednisone or dexamethasone remains unclear. This study compares patient characteristics and ED reutilization/hospital readmission outcomes of dexamethasone, prednisone, and combination therapy for inpatient asthma management. METHODS: A retrospective study was conducted at our tertiary children's hospital of children aged 2 to 18 years hospitalized between March 2016 and December 2018 with a primary discharge diagnosis of asthma, reactive airway disease, or bronchospasm. The differences between steroid groups were compared using Fisher's exact or Chi-square tests for categorical variables, and a Kruskal-Wallis test for continuous variables. A multivariable logistic regression was performed to analyze ED reutilization and hospital readmission rates. RESULTS: 1697 subjects met inclusion criteria. 115 (6.8%) patients received dexamethasone, 597 (35.2%) received prednisone, and 985 (58.0%) received combination therapy. Patients prescribed combination therapy had a lower exacerbation severity than patients prescribed prednisone, but higher severity than patients prescribed dexamethasone (p < .001, p = .001, respectively). Dexamethasone and combination therapy were not associated with increased 30-day ED reutilization/hospital readmissions compared to prednisone (p > .05). CONCLUSIONS: In our study, most patients hospitalized for status asthmaticus received combination therapy. Despite the differences in severity between steroid groups, outcomes of combination therapy and dexamethasone monotherapy, as measured by frequency of ED reutilizations/hospital readmissions, are comparable to prednisone monotherapy.

10.
Pediatr Cardiol ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842557

RESUMO

Pulmonary vein stenosis (PVS) is a rare, serious, and progressive disease in the pediatric population. Evaluation is complex and involves multimodality imaging. Diagnosis is important as early treatment to prevent progressive pulmonary hypertension and right ventricular dysfunction is essential. Adult studies have shown good correlation between various imaging modalities; however, there are limited data in children. This is a single-center retrospective pilot study to determine the reliability of measurement of pulmonary vein stenosis and pulmonary hypertension across different imaging modalities-computed tomography angiography (CTA), echocardiography (echo), lung perfusion scan (LPS), and cardiac catheterization (cath). PVS was defined as > 2 mmHg by echo and cath and/or 50% reduction in diameter by CTA. Patients had to have an echo, CTA and cath performed within a 1-month timeframe of one another to be included in the study, with LPS data included if testing was completed at initial evaluation. Fifteen total patients were enrolled; 87% were categorized as primary PVS; a condition not directly related to direct injury or prior surgical intervention. Twenty-seven total stenotic pulmonary veins were identified (mean 1.8, range 1-4). CTA had a slightly better agreement with cath than echo in identifying PVS in different vein locations except in the LLPV. Additionally, echo and CTA had excellent sensitivity (91%) and specificity (100%) compared to cath for diagnosis of PH. We conclude that non-invasive imaging of echo and CTA has an acceptable correlation to cardiac catheterization for screening and initial evaluation of PVS and PH, as directly related to PVS, in pediatrics.

11.
J Environ Manage ; 352: 120037, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38194872

RESUMO

Herbicide abuse has a significantly negative impact on soil microflora and further influences the ecological benefit. The regulating measures and corresponding mechanisms mitigating the decreased bacterial diversity due to herbicide use have rarely been studied. A field experiment containing the application gradient of an efficient maize herbicide thiencarbazone-methyl·isoxaflutole was performed. The relationship between soil bacterial community and thiencarbazone-methyl·isoxaflutole use was revealed. Modified attapulgite was added to explore its impacts on soil microflora under the thiencarbazone-methyl·isoxaflutole application. Based on the analytic network process-entropy weighting method-TOPSIS method model, the ecological benefit focusing on microbial responses was quantitatively estimated along with technical effectiveness and economic benefit. The results showed that the diversity indices of soil microflora, especially the Inv_Simpson index, were reduced at the recommended, 5 and 10 times the recommended dosages of thiencarbazone-methyl·isoxaflutole use. The Flavisolibacter bacteria was negatively correlated with the residues in soils based on the random forest model and correlation analysis, indicating a potential degrader of thiencarbazone-methyl·isoxaflutole residues. The structural equation model further confirmed that the high soil water content and soil pH promoted the function of Flavisolibacter bacteria, facilitated the dissipation of thiencarbazone-methyl·isoxaflutole residues and further improved the diversity of soil microflora. In addition, the presence of modified attapulgite was found to increase the soil pH, which may improve bacterial diversity through the regulating pathway. This explained the high ecological benefits of the treatment where the thiencarbazone-methyl·isoxaflutole was applied at the recommended dosage rates in conjunction with modified attapulgite addition. Therefore, the comprehensive benefits of thiencarbazone-methyl·isoxaflutole application with a focus on ecological benefits can be improved by regulating the soil pH with modified attapulgite.


Assuntos
Herbicidas , Isoxazóis , Compostos de Magnésio , Compostos de Silício , Herbicidas/química , Solo , Bactérias/metabolismo , Microbiologia do Solo
12.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(2): 273-278, 2024 Apr 18.
Artigo em Zh | MEDLINE | ID: mdl-38595244

RESUMO

OBJECTIVE: To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus (SLE) in a real-world setting, and to analyze the related factors of low disease activity and clinical remission. METHODS: One thousand patients with SLE were enrolled from 11 teaching hospitals. Demographic, clinical and laboratory data, as well as treatment regimes were collec-ted by self-completed questionnaire. The rates of low disease activity and remission were calculated based on the lupus low disease activity state (LLDAS) and definitions of remission in SLE (DORIS). Charac-teristics of patients with LLDAS and DORIS were analyzed. Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission. RESULTS: 20.7% of patients met the criteria of LLDAS, while 10.4% of patients achieved remission defined by DORIS. Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration, compared with non-remission group. Moreover, the rates of anemia, creatinine elevation, increased erythrocyte sedimentation rate (ESR) and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group. Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission. The results of Logistic regression analysis showed that increased ESR, positive anti-dsDNA antibodies, low level of complement (C3 and C4), proteinuria, low household income were negatively related with LLDAS and DORIS remission. However, hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission. CONCLUSION: LLDAS and DORIS remission of SLE patients remain to be improved. Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.


Assuntos
Hidroxicloroquina , Lúpus Eritematoso Sistêmico , Humanos , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Imunossupressores/uso terapêutico , Índice de Gravidade de Doença
13.
Int Wound J ; 21(4): e14608, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38151912

RESUMO

Management of postoperative pain is of vital importance for patients undergoing Video-Assisted Thoracoscopic Surgery (VATS) for Pulmonary Carcinoma Resection. The study evaluates the impact of Paravertebral Nerve Blockade (PNB) in conjunction with general anaesthesia on postoperative pain relief, as compared with general anaesthesia alone. A retrospective analysis was carried out from May 2020 to May 2023, involving 100 patients with pathologically confirmed pulmonary carcinoma. The patients were divided into two groups: a control group that received general anaesthesia and an observation group that received a combination of general anaesthesia and PNB. The intensity of postoperative pain was assessed at various time intervals using the visual analogue scale (VAS), while the effectiveness of patient-controlled analgesia was also evaluated. Additionally, the study examined the incidence rates of chronic pain in the postoperative period. Statistical analysis was performed using IBM SPSS version 27.0. Significant reductions in VAS scores for both resting and cough-induced pain were observed in the observation group at 2 and 6 h post-operation (p < 0.01). However, the difference diminished over time. The observation group had fewer patient-controlled analgesia activations and required lower dosages of hydromorphone at both 24- and 48-h post-operation. The incidence of chronic pain was also significantly lower in the observation group (24.00%) compared with the control group (54.00%) (p < 0.01). PNB, when administered in combination with general anaesthesia, significantly reduces immediate postoperative pain and the requirement for additional analgesics in patients undergoing VATS for pulmonary carcinoma resection. The effect diminishes over time but has a lasting impact on reducing the incidence of chronic postoperative pain.


Assuntos
Carcinoma , Dor Crônica , Bloqueio Nervoso , Ferida Cirúrgica , Humanos , Cirurgia Torácica Vídeoassistida , Manejo da Dor , Estudos Retrospectivos , Dor Pós-Operatória/tratamento farmacológico
14.
Angew Chem Int Ed Engl ; 63(7): e202318043, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38135669

RESUMO

A key task in today's inorganic synthetic chemistry is to develop effective reactions, routes, and associated techniques aiming to create new functional materials with specifically desired multilevel structures and properties. Herein, we report an ultrathin two-dimensional layered composite of graphene ribbon and silicate via a simple and scalable one-pot reaction, which leads to the creation of a novel carbon-metal-silicate hybrid family: carbosilicate. The graphene ribbon is in situ formed by unzipping carbon nanotubes, while the ultrathin silicate is in situ obtained from bulk silica or commercial glass; transition metals (Fe or Ni) oxidized by water act as bridging agent, covalently bonding the two structures. The unprecedented structure combines the superior properties of the silicate and the nanocarbon, which triggers some specific novel properties. All processes during synthesis are complementary to each other. The associated synergistic chemistry could stimulate the discovery of a large class of more interesting, functionalized structures and materials.

15.
Clin Immunol ; 255: 109749, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37657525

RESUMO

An investigator-initiated, multicentre, randomized, double-blind, triple-dummy, controlled trial was conducted at 14 tertiary rheumatology centers in China to evaluate the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) with recombinant human TNF receptor IgGFc fusion protein (rhTNFR-Fc) in active Rheumatoid Arthritis (RA). Primary endpoint was the proportion of patients achieved a 50% improvement of American College of Rheumatology criteria (ACR50) in TwHF+rhTNFR-Fc vs. methotrexate (MTX) group at week 12. ACR50 was achieved in 57.1% (72/126), 41.3% (52/126), 23.0% (29/126), and 26.2% (33/126) patients receiving TwHF+rhTNFR-Fc, MTX + rhTNFR-Fc, TwHF and MTX monotherapy, respectively, at week 12 (TwHF+rhTNFR-Fc vs. other three groups, all p < 0.05). No statistical difference in serious adverse events or adverse events leading to discontinuation of study across all groups was documented. TwHF+rhTNFR-Fc was superior to MTX for active RA, and was more effective than MTX + rhTNFR-Fc on ACR50, with a similar safety profile. Trial registration:ClinicalTrials.govNCT03589833.

16.
Clin Exp Immunol ; 214(1): 36-49, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-37422711

RESUMO

Esophageal squamous cell carcinoma (ESCC), one of the most commonly diagnosed and lethal malignant diseases, has a complex tumor ecosystem. An obvious requirement for T-cell-mediated tumor control is the infiltration of tumor-reactive T cells into the tumor. Here, we obtained detailed T-cell compositions in both ESCC tumors and matched peripheral blood mononuclear cells (PBMCs) at single-cell resolution. We demonstrated that T cells in tumors and PBMCs had different compositions and functional states. ESCC tumors were rich in Treg and exhausted T cells but poor in cytotoxic and naïve T cells compared with PBMCs. The exhausted T cells showed higher exhausted signature in tumors than in PBMCs, while the cytotoxic T cells exhibited higher cytotoxic signature in PBMCs than in tumors. Our data indicated an immunosuppressive status and a defect at the level of T-cell priming in the tumor microenvironment. Leukocyte-associated Ig-like receptor-2 (LAIR2), a soluble collagen receptor that prevents the binding of human leukocyte-associated Ig-like receptor-1 (LAIR1) to collagens, was predominantly expressed in proliferating CD8+ T and Treg cells in tumors but in cytotoxic cells in PBMCs. LAIR2 could inhibit tumor metastasis, invasion, and collagen deposition via suppressing transforming growth factor-ß signaling. These findings revealed differential T-cell populations in tumors and PBMCs and provided convincing evidence that LAIR2 acted as a tumor suppressor.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/patologia , Leucócitos Mononucleares/patologia , Ecossistema , Linfócitos T Reguladores , Microambiente Tumoral
17.
Exp Eye Res ; 235: 109628, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37619828

RESUMO

Preventing postoperative bleb scar formation is an effective way of improving glaucoma filtration surgery (GFS) outcome. Use of more effective antifibrotic drugs with fewer adverse effects may be a good way to address the problem. In the present study, we use a primary cell model, consisting of Tenon's fibroblasts obtained from patients with glaucoma, which were stimulated with TGF-ß1 to induce the fibrotic phenotype. We explored the effects of niclosamide on TGF-ß1-induced fibrosis in these cells and examined its underlying mechanism of action. A transcriptome sequencing assay was used to explore possible signaling pathways involved. Niclosamide inhibited cell proliferation and migration, and decreased the levels of alpha-smooth muscle actin, type I and type III collagen in human Tenon's fibroblasts induced by TGF-ß1. Niclosamide also induced apoptosis and counteracted TGF-ß1-induced cytoskeletal changes and extracellular matrix accumulation. Moreover, niclosamide decreased TGF-ß1-induced phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) protein expression in human Tenon's fibroblasts. The results indicate that niclosamide inhibits TGF-ß1-induced fibrosis in human Tenon's fibroblasts by blocking the MAPK-ERK1/2 signaling pathway. Thus, niclosamide is a potentially promising antifibrotic drug that could improve glaucoma filtration surgery success rate.


Assuntos
Glaucoma , Niclosamida , Fator de Crescimento Transformador beta1 , Humanos , Proliferação de Células , Células Cultivadas , Cicatriz/metabolismo , Fibroblastos/metabolismo , Fibrose , Glaucoma/metabolismo , Sistema de Sinalização das MAP Quinases , Niclosamida/farmacologia , Cápsula de Tenon/metabolismo , Fator de Crescimento Transformador beta1/efeitos adversos
18.
Inflamm Res ; 72(12): 2089-2109, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37878024

RESUMO

OBJECTIVE: The pathogenesis, diagnosis, and treatment of Sjögren's syndrome (SS) face many challenges, and there is an urgent need to develop new technologies to improve our understanding of SS. METHODS: By searching the literature published domestically and internationally in the past 20 years, this artical reviewed the research of various omics techniques in SS. RESULTS: Omics technology provided valuable insights into the pathogenesis, early diagnosis, condition and efficacy evaluation of SS. It is helpful to reveal the pathogenesis of the disease and explore new treatment schemes, which will open a new era for the study of SS. CONCLUSION: At present, omics research has made some gratifying achievements, but there are still many uncertainties. Therefore, in the future, we should improve research techniques, standardize the collection of samples, and adopt a combination of multi-omics techniques to jointly study the pathogenesis of SS and provide new schemes for its treatment.


Assuntos
Multiômica , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/genética , Síndrome de Sjogren/diagnóstico
19.
Inflamm Res ; 72(6): 1291-1301, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37300584

RESUMO

OBJECTIVE: To review the preparation, characteristics and research progress of different PsA animal models. METHODS: Computerized searches were conducted in CNKI, PubMed and other databases to classify and discuss the relevant studies on PsA animal models. The search keywords were "PsA and animal model(s), PsA and animal(s), PsA and mouse, PsA and mice, PsA and rat(s), PsA and rabbit(s), PsA and dog(s)" RESULTS: The experimental animals currently used to study PsA are mainly rodents, including mice and rats. According to the different methods of preparing the models, the retrieved animal models were classified into spontaneous or genetic mutation, transgenic and induced animal models. These PsA animal models involve multiple pathogenesis, some experimental animals' lesions appear in a short and comprehensive cycle, some have a high success rate in molding, and some are complex and less reproducibility. This article summarizes the preparation methods, advantages and disadvantages of different models. CONCLUSIONS: The animal models of PsA aim to mimic the clinicopathological alterations of PsA patients through gene mutation, transgenesis or targeted proinflammatory factor and to reveal new pathogenic pathways and therapeutic targets by exploring the pathological features and clinical manifestations of the disease. This work will have very far-reaching implications for the in-depth understanding of PsA and the development of new drugs.


Assuntos
Artrite Psoriásica , Psoríase , Camundongos , Ratos , Animais , Cães , Coelhos , Artrite Psoriásica/genética , Artrite Psoriásica/tratamento farmacológico , Psoríase/tratamento farmacológico , Reprodutibilidade dos Testes , Modelos Animais , Fatores de Risco
20.
J Org Chem ; 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37607402

RESUMO

ortho-Phthalaldehyde (OPA) with high reactivity to the amine group has been widely used to modify proteins. We discovered new modifications of OPA and 2-acylbenzaldehyde and proposed the reaction mechanism. Using isotope labeling mass spectrometry-based experiment, we identified new cross-linking properties of OPA and 2-acylbenzaldehyde. This reactivity revealed that OPA has the potential to probe proximal amino acids in biological systems.

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