Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.060
Filtrar
1.
Adv Colloid Interface Sci ; 332: 103264, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39116585

RESUMO

MXenes belong to one of the recently developed advanced materials with tremendous potential for diverse sensing applications. To date, various types of MXene-based materials have been developed to generate direct/indirect ultrasensitive sensing signals against various forms of analytes via fluorescence quenching or enhancement. In this work, the fluorescence sensing/biosensing capabilities of the MXene-based materials have been explored and evaluated against a list of ionic/emerging pollutants in environment and food matrices. The suitability of an MXene-based sensing approach is also validated through the assessment of the performance based on the basic quality assurance parameters, e.g., limit of detection (LOD), sensing range, and response time. Accordingly, the best performing MXene-based materials are selected and recommended for the given target(s) to help facilitate their scalable applications under real-world conditions.

2.
Medicine (Baltimore) ; 103(32): e39139, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39121273

RESUMO

Calcinosis cutis is classified into 5 main types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. However, it is occasionally misdiagnosed as a malignancy and its management remains challenging. Therefore, in this study, we report our diagnostic and treatment experiences with patients with calcinosis cutis and suggest strategies for improving patient care. This retrospective study included 7 patients (4 men, 3 women; 44.4 ±â€…32.0 years old) who visited our hospital between March 2013 and December 2022 and were diagnosed with calcinosis cutis through histopathological procedures. The patients underwent complete excision of the mass without a safety margin. Frozen biopsy was not performed during surgery. No significant intraoperative or postoperative complications were noted after the application of various imaging techniques for diagnosis and follow-up. All patients showed complete recovery. Follow-up showed no recurrence or complications in the 6 patients who completed 1 year of follow-up. Radiological tests such as plain radiography, ultrasonography, computed tomography, and magnetic resonance imaging are important for accurate diagnosis and treatment of calcinosis cutis. This approach can ensure precise assessment of preoperative lesions, leading to safe and less invasive patient treatment, recurrence prevention, and complications of calcinosis cutis.


Assuntos
Calcinose , Dermatopatias , Humanos , Calcinose/diagnóstico , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Estudos Retrospectivos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Dermatopatias/diagnóstico , Dermatopatias/patologia , Dermatopatias/cirurgia , Calcinose Cutânea
3.
J Hazard Mater ; 478: 135412, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39126855

RESUMO

A prototype air purifier (AP) module has been constructed using bismuth-doped titanium dioxide (Bix-P25: x(%) as Bi/Ti molar ratios of 1.1, 2.1, 3.3, 5.3, and 8.7). The reactive adsorption property of Bix-P25 materials is evaluated against H2S gas at a recirculation rate of 160 L min-1 in a 17 L closed chamber. The AP (Bi5.3-P25) exhibits superior performance against 10 ppm H2S in dry air under dark conditions (i.e., without light irradiation), with a removal efficiency (XH2S)= 99% in 5 mins, reaction kinetic rate (r (at X = 10%))= 7.3 mmol h-1g-1, and partition coefficient= 0.18 mol kg-1 Pa-1. As such, its superiority is evident over the reference AP (P25) filter with XH2S < 10%. The clean air delivery rate (CADR) of AP (Bi5.3-P25) increases noticeably from 9.9 to 17.8 L min-1 with increasing relative humidity (RH) from 0 to 80%, respectively. In contrast, the CADR decreases from 9.9 to 5.8 L min-1 as the H2S increases from 10 to 20 ppm. According to density functional theory (DFT), the presence of H2O vapor enhances the hydroxylation of Bix-P25 surface to promote H2S mineralization through the formation of TiS3 (i.e., thermodynamic reaction of S atom with the catalytic surface). Complete removal of H2S on the Bi5.3-P25 surface is also confirmed consistently through gas chromatography-mass spectrometry (GC-MS), in-situ diffuse reflection infrared spectroscopy (in-situ DRIFTS), and elemental analysis (EA). This work represents the first utilization of Bix-P25 materials fabricated on an AP platform toward the desulfurization of H2S at room temperature (RT). The practical utility of Bix-P25 is overall validated by its eminent role in reactive adsorption and catalytic oxidation (RACO) of H2S from the air.

4.
Chem Biol Interact ; : 111192, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39127184

RESUMO

The genus Salix spp. has long been recognized as a healing herb for its use in treating fever, inflammation, and pain relief, as well as a food source for its nutritional value. In this study, we aimed to explore the potential bioactive natural products in the leaves of Salix chaenomeloides, commonly known as Korean pussy willow, for their protective effects against skin damage, including aging. Utilizing LC/MS-guided chemical analysis of the ethanol extract of S. chaenomeloides leaves, with a focus on major compounds, we successfully isolated two main phenolic compounds, tremulacin (1) and tremuloidin (2). Subsequently, we investigated the protective effects of tremulacin (1) and tremuloidin (2) in TNF-α-stimulated human dermal fibroblasts (HDFs). The results revealed that both tremulacin (1) and tremuloidin (2) inhibited TNF-α-stimulation-induced ROS, suppressed matrix metalloproteinase-1 (MMP-1) expression, and enhanced collagen secretion. This implies that both tremulacin (1) and tremuloidin (2) hold promise as preventive agents against photoaging-induced skin aging. Furthermore, we assessed the activity of mitogen-activated protein kinases (MAPKs), cyclooxygenase-2 (COX-2), and heme oxygenase 1 (HO-1) to elucidate the mechanism of photoaging inhibition by tremuloidin (2), which exhibited superior efficacy. We found that tremuloidin (2) inhibited ERK and p38 phosphorylation and notably suppressed COX-2 expression while significantly upregulating HO-1 expression. These findings suggest potent anti-inflammatory and antioxidant properties of tremuloidin (2), positioning it as a potential candidate for combating photoaging-induced skin aging.

5.
Sci Immunol ; 9(97): eadn6509, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39028827

RESUMO

Most patients treated with US Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T cells eventually experience disease progression. Furthermore, CAR T cells have not been curative against solid cancers and several hematological malignancies such as T cell lymphomas, which have very poor prognoses. One of the main barriers to the clinical success of adoptive T cell immunotherapies is CAR T cell dysfunction and lack of expansion and/or persistence after infusion. In this study, we found that CD5 inhibits CAR T cell activation and that knockout (KO) of CD5 using CRISPR-Cas9 enhances the antitumor effect of CAR T cells in multiple hematological and solid cancer models. Mechanistically, CD5 KO drives increased T cell effector function with enhanced cytotoxicity, in vivo expansion, and persistence, without apparent toxicity in preclinical models. These findings indicate that CD5 is a critical inhibitor of T cell function and a potential clinical target for enhancing T cell therapies.


Assuntos
Antígenos CD5 , Imunoterapia Adotiva , Linfócitos T , Animais , Imunoterapia Adotiva/métodos , Antígenos CD5/imunologia , Camundongos , Humanos , Linfócitos T/imunologia , Linfócitos T/transplante , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Linhagem Celular Tumoral , Sistemas CRISPR-Cas , Feminino
6.
J Nat Prod ; 87(7): 1881-1887, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-38950087

RESUMO

A family of pyrazinone metabolites (1-11) were characterized from Staphylococcus xylosus ATCC 29971. Six of them were hydroxylated or methoxylated, which were proposed to be produced by the rare noncatalytic oxa-Michael addition reaction with a water or methanol molecule. It was confirmed that isopropyl alcohol can also be the Michael donor of the reaction. 1-7 and the synthetic precursor 2a showed significant inhibition of breast cancer cell migration.


Assuntos
Pirazinas , Staphylococcus , Humanos , Movimento Celular/efeitos dos fármacos , Estrutura Molecular , Pirazinas/química , Pirazinas/farmacologia , Staphylococcus/efeitos dos fármacos
7.
J Hazard Mater ; 476: 135016, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38986407

RESUMO

Formaldehyde (FA) is a hazardous indoor air pollutant with carcinogenic propensity. Oxidation of FA in the dark at low temperature (DLT) is a promising strategy for its elimination from indoor air. In this light, binary manganese-cobalt oxide (0.1 to 5 mol L-1-MnCo2O4) is synthesized and modified in an alkaline medium (0.1-5 mol L-1 potassium hydroxide) for FA oxidation under room temperature (RT) conditions. Accordingly, 1-MnCo2O4 achieves 100 % FA conversion at RT (50 ppm and 7022 h-1 gas hourly space velocity (GHSV)). The catalytic activity of 1-MnCo2O4 is assessed further as a function of diverse variables (e.g., catalyst mass, relative humidity, FA concentration, molecular oxygen (O2) content, flow rate, and time on-stream). In situ diffuse reflectance infrared Fourier-transform spectroscopy confirms that FA molecules are adsorbed onto the active surface sites of 1-MnCo2O4 and oxidized into water (H2O) and carbon dioxide (CO2) through dioxymethylene (DOM) and formate (HCOO-) as the reaction intermediates. According to the density functional theory simulations, the higher catalytic activity of 1-MnCo2O4 can be attributed to the combined effects of its meritful surface properties (e.g., the firmer attachment of FA molecules, lower energy cost of FA adsorption, and lower desorption energy for CO2 and H2O). This work is the first report on the synthesis of alkali (KOH)-modified MnCo2O4 and its application toward the FA oxidative removal at RT in the dark. The results of this study are expected to provide valuable insights into the development of efficient and cost-effective non-noble metal catalysts against indoor FA at DLT.

8.
Environ Res ; 260: 119664, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39048069

RESUMO

The preparation of nitrogen-doped TiO2 (i.e., N-TiO2) catalysts is a highly effective option to improve the photocatalytic activity of TiO2. Nonetheless, relatively little is known about the effects of dopant precursors selected for their preparation with regard to the photocatalytic efficacy. In this study, three types of dopants are selected and used as N sources (urea (U), melamine (M), and aqueous ammonia (A)) for N-TiO2 samples with the name codes of NTU, NTM, and NTA, respectively. The photocatalytic efficacy of these N-TiO2 samples is examined against toluene in a packed bed flow reactor. Under optimal conditions (e.g., relative humidity (RH) = 20% and gas hourly space velocity (GHSV) = 1698 h-1), the superiority of NTA is evident over others with a quantum efficiency (QE) of 7.03 × 10-4 molecules photon-1, a space time yield (STY) of 1.38 × 10-4 molecules photon-1 mg-1, and a specific clean air delivery rate (SCADR) of 1148.8 L g-1 h-1. The analysis based on in-situ diffuse reflectance infrared Fourier transform spectroscopy and gas chromatography-mass spectrometry confirms the formation of several intermediates such as benzyl alcohol, benzaldehyde, benzoic acid, and alkane species through ring opening reactions. In addition, the prepared NTA photocatalyst exhibits the highest toluene photocatalytic degradation efficiency among all TiO2-based catalysts surveyed to date. Overall, this study offers as a valuable guideline for the development of advanced TiO2 catalytic systems (such as N-TiO2) for the treatment of aromatic hydrocarbons in indoor air.

9.
J Ethnopharmacol ; 333: 118398, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38823660

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Wikstroemia has been extensively utilized in traditional Chinese medicine (TCM) for the management of conditions such as coughs, edema, arthritis, and bronchitis. Studies have indicated that the crude extracts of Wikstroemia exhibit anti-inflammatory, anti-allergy, anti-aging, skin psoriasis, anti-cancer, and antiviral properties. In addition, these extracts are known to contain bioactive substances, including flavonoids, coumarins, and lignans. However, few studies have investigated the anti-inflammatory or anti-allergic activities of Wikstroemia trichotoma (Thunb.) Makino against atopic dermatitis (AD). AIM OF THE STUDY: The study aimed to explore the potential of a 95% ethanol extract of W. trichotoma (WTE) on the dysfunction of skin barrier and immune system, which are primary symptoms of AD, in 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice and phorbol 12-myristate 13-acetate (PMA)/ionomycin or immunoglobulin E (IgE) + 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulated rat basophilic leukemia cell line (RBL-2H3). Furthermore, we sought to identify the chemical contents of WTE using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA). MATERIALS AND METHODS: An in vitro study was conducted using RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA to assess the inhibitory effects of WTE on mast cell degranulation and interleukin-4 (IL-4) mRNA expression levels. For the in vivo study, AD was induced in SKH-1 hairless mice by applying 1% DNCB to the dorsal skin daily for 7 days. Subsequently, 0.1% DNCB solution was applied on alternate days, and mice were orally administered WTE (at 30 or 100 mg/kg/day) dissolved in 0.5% carboxymethyl cellulose (CMC) daily for 2 weeks. Transepidermal water loss (TEWL), skin hydration, skin pH, and total serum IgE levels were measured. RESULTS: In DNCB-stimulated SKH-1 hairless mice, WTE administration significantly improved AD symptoms and ameliorated dorsal skin inflammation. Oral administration of WTE led to a significant decrease in skin thickness, infiltration of mast cells, and level of total serum IgE, thus restoring skin barrier function in the DNCB-induced skin lesions. In addition, WTE inhibited ß-hexosaminidase release and reduced IL-4 mRNA levels in RBL-2H3 cells. Chemical profile analysis of WTE confirmed the presence of three phenolic compounds, viz. chlorogenic acid, miconioside B, and matteucinol-7-O-ß-apiofuranosyl (1 â†’ 6)-ß-glucopyranoside. CONCLUSIONS: WTE ameliorates AD symptoms by modulating in the skin barrier and immune system dysfunction. This suggests that W. trichotoma extract may offer therapeutic benefits for managing AD.


Assuntos
Dermatite Atópica , Dinitroclorobenzeno , Modelos Animais de Doenças , Etanol , Imunoglobulina E , Extratos Vegetais , Wikstroemia , Animais , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/induzido quimicamente , Wikstroemia/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Camundongos , Etanol/química , Imunoglobulina E/sangue , Camundongos Pelados , Anti-Inflamatórios/farmacologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Feminino , Antialérgicos/farmacologia , Linhagem Celular Tumoral , Pele/efeitos dos fármacos , Pele/patologia , Pele/metabolismo , Masculino , Interleucina-4/metabolismo
10.
BMC Public Health ; 24(1): 1656, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38902653

RESUMO

INTRODUCTION: Although the risk of CVD is increased in cancer survivors, few studies have investigated the CVD risk in survivors of gastrointestinal (GI) cancer. Therefore, we evaluated the CVD risk using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score for GI cancer survivors and associated physical activity factors. METHODS: Using the 2014-2019 Korean National Health and Nutrition Examination Surveys, data were collected for 262 GI cancer survivors and 1,310 cancer-free controls matched at a 1:5 ratio based on age and sex. The International Physical Activity Questionnaire Short-Form was used to assess physical activity, and the Euro QoL Questionnaire 5-Dimensional Classification (EQ-5D) was used to assess the health-related quality of life. RESULTS: A multiple logistic regression analysis demonstrated a lower risk of ASCVD in GI cancer survivors than in controls (adjusted odds ratio [aOR] = 0.73, 95% confidence interval [CI] = 0.55-0.97). Moreover, the risk of having a high ASCVD score was significantly lower in individuals who performed sufficient aerobic physical activity (aOR = 0.59, 95% CI = 0.47-0.75) and those with an EQ-5D score 1 or 2 (aOR = 0.36, 95% CI = 0.20-0.65 and aOR = 0.31, 95% CI = 0.16-0.58, respectively). CONCLUSIONS: This population-based study demonstrated that engaging in sufficient physical activity can reduce the ASCVD risk among GI cancer survivors.


Assuntos
Sobreviventes de Câncer , Doenças Cardiovasculares , Exercício Físico , Neoplasias Gastrointestinais , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Sobreviventes de Câncer/estatística & dados numéricos , Sobreviventes de Câncer/psicologia , Pessoa de Meia-Idade , Neoplasias Gastrointestinais/psicologia , República da Coreia/epidemiologia , Doenças Cardiovasculares/epidemiologia , Idoso , Adulto , Qualidade de Vida , Fatores de Risco , Estudos de Casos e Controles , Medição de Risco
11.
Chemosphere ; 361: 142550, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38857633

RESUMO

Materials Institute Lavoisier (MIL) metal organic frameworks (MOFs) are known for their potential to adsorb gaseous organic pollutants. This study explores the synergistic effects between the selection of central metals (e.g., titanium, iron, and aluminum) and the incorporation of -NH2 groups in terms of adsorption efficiency against gaseous formaldehyde (FA). A group of the pristine MIL MOFs is synthesized using three different metals (i.e., titanium, iron, and aluminum) and terephthalic acid along with their NH2 derivatives using 2-aminoterephthalic acid. Among the pristine forms, MIL-125(Ti) achieves the highest FA adsorption capacity (Q) of 26.96 mg g-1 and a partition coefficient (PC) of 0.0898 mol kg-1 Pa-1. Further, amination significantly improves the FA adsorption potential of NH2-MIL-125(Ti) with a Q value of 91.22 mg g-1 (PC = 0.3038 mol kg-1 Pa-1). In situ diffuse reflectance infrared Fourier-transform spectroscopy reveals that the FA adsorption of plain MILs should be governed primarily by physisorption. In contrast, FA adsorption of NH2-MILs appears to be regulated by both physisorption and chemisorption, while the latter being affected mainly through FA-NH2 interactions (Schiff base reactions). These findings provide valuable insights into the utility of aminated MIL sorbents, possibly toward the efficient management of indoor air quality.


Assuntos
Poluentes Atmosféricos , Formaldeído , Estruturas Metalorgânicas , Formaldeído/química , Adsorção , Estruturas Metalorgânicas/química , Poluentes Atmosféricos/química , Titânio/química , Alumínio/química , Espectroscopia de Infravermelho com Transformada de Fourier , Ferro/química
12.
Res Sq ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38853999

RESUMO

Human lung cancer carries high genetic alterations, expressing high tumor-specific neoantigens. Although orthotopic murine lung cancer models recapitulate many characteristics of human lung cancers, genetically engineered mouse models have fewer somatic mutations than human lung cancer, resulting in scarce immune cell infiltration and deficient immune responses. The endogenous mouse lung cancer model driven by Kras mutation and Trp53 deletion (KP model) has minimal immune infiltration because of a scarcity of neoantigens. Fine-tuning tumor antigenicity to trigger the appropriate level of antitumor immunity would be key to investigating immune responses against human lung cancer. We engineered the KP model to express antigens of OVA peptides (minOVA) as neoantigens along with ZsGreen, a traceable fluorescent conjugate. The KP model expressing minOVA exhibited stronger immunogenicity with higher immune cell infiltration comprised of CD8+ T cells and CD11c+ dendritic cells (DCs). Consequentially, the KP model expressing minOVA exhibits suppressed tumor growth compared to its origin. We further analyzed tumor-infiltrated DCs. The majority of ZsGreen conjugated with minOVA was observed in the conventional type 2 DCs (cDC2), where cDC1 has minimal. These data indicate that tumor immunogenicity regulates host immune responses, and tumor neoantigen is mostly recognized by cDC2 cells, which may play a critical role in initiating anti-tumor immune responses in an orthotopic murine lung cancer model.

13.
Food Chem Toxicol ; 190: 114794, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38849046

RESUMO

Phytochemical analysis of the methanolic extracts of Jatropha podagrica stalks and roots using liquid chromatography-mass spectrometry (LC-MS) led to the isolation of six compounds: corchoionoside C (1), isobiflorin (2), fraxin (3), hovetrichoside C (4), fraxetin (5), and corillagin (6). The isolated compounds (1-6) were tested for their cytotoxicity against MDA-MB-231 human breast cancer cells. Remarkably, compound 4 (hovetrichoside C) exhibited robust cytotoxicity against MDA-MB-231 cells, displaying an IC50 value of 50.26 ± 1.22 µM, along with an apoptotic cell death rate of 24.21 ± 2.08% at 100 µM. Treatment involving compound 4 amplified protein levels of cleaved caspase-8, -9, -3, -7, BH3-interacting domain death agonist (Bid), Bcl-2-associated X protein (Bax), and cleaved poly (ADP-ribose) polymerase (cleaved PARP), while concurrently reducing B-cell lymphoma 2 (Bcl-2) levels. In totality, these findings underscore that hovetrichoside C (4) possesses anti-breast cancer activity that revolves around apoptosis induction via both extrinsic and intrinsic signaling pathways.


Assuntos
Apoptose , Neoplasias da Mama , Jatropha , Humanos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Jatropha/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124752, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38945007

RESUMO

Serum creatinine (CR) is regarded as one of the most sought out prognostic biomarkers in medical evaluation of chronic kidney disease (CKD). In light of the diagnostic significance of CR, the utility of a fluorescence biosensor for its detection in human urine specimens has been explored based on Förster resonance energy transfer (FRET) across nitrogen-doped carbon dots (N-CDs) and gold nanoparticles (GNPs). A straightforward microwave-assisted synthesis procedure has been adopted to prepare N-CDs (λexcitation = 400 nm, λemission = 540 ± 5 nm) with bright green emissions. On addition of pre-synthesized GNPs, the radiative emanation of the N-CDs is completely suppressed on account of FRET across the N-CDs and the GNPs. About 77 % of their fluorescence intensity is recovered after adding CR to GNPs@N-CDs nanocomposite. The limit of detection for CR sensing is estimated as 0.02 µg•mL-1. This biosensor is selective enough to recognize CR in the existence of potential interfering substances (e.g., ascorbic acid, glucose, glutathione, urea, and electrolytes). Its practical utility for CR detection has been validated further on the basis of satisfactory correlation with the benchmark Jaffe method, as observed in artificial/human urine specimens. Consequently, this manuscript marks a pioneering report on employing CDs and GNPs-based FRET for identifying CR in urine specimens of CKD patients.


Assuntos
Carbono , Creatinina , Transferência Ressonante de Energia de Fluorescência , Ouro , Nanopartículas Metálicas , Nitrogênio , Pontos Quânticos , Humanos , Transferência Ressonante de Energia de Fluorescência/métodos , Ouro/química , Carbono/química , Nanopartículas Metálicas/química , Pontos Quânticos/química , Creatinina/urina , Nitrogênio/química , Limite de Detecção , Técnicas Biossensoriais/métodos
15.
Commun Chem ; 7(1): 129, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849519

RESUMO

Fungi constitute the Earth's second most diverse kingdom, however only a small percentage of these have been thoroughly examined and categorized for their secondary metabolites, which still limits our understanding of the ecological chemical and pharmacological potential of fungi. In this study, we explored members of the co-evolved termite-associated fungal genus Xylaria and identified a family of highly oxygenated polyketide-terpene hybrid natural products using an MS/MS molecular networking-based dereplication approach. Overall, we isolated six no yet reported xylasporin derivatives, of which xylasporin A (1) features a rare cyclic-carbonate moiety. Extensive comparative spectrometric (HRMS2) and spectroscopic (1D and 2D NMR) studies allowed to determine the relative configuration across the xylasporin family, which was supported by chemical shift calculations of more than 50 stereoisomers and DP4+ probability analyses. The absolute configuration of xylasporin A (1) was also proposed based on TDDFT-ECD calculations. Additionally, we were able to revise the relative and absolute configurations of co-secreted xylacremolide B produced by single x-ray crystallography. Comparative genomic and transcriptomic analysis allowed us to deduce the putative biosynthetic assembly line of xylasporins in the producer strain X802, and could guide future engineering efforts of the biosynthetic pathway.

16.
Nat Immunol ; 25(6): 1020-1032, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38831106

RESUMO

The efficacy of T cell-based immunotherapies is limited by immunosuppressive pressures in the tumor microenvironment. Here we show a predominant role for the interaction between BTLA on effector T cells and HVEM (TNFRSF14) on immunosuppressive tumor microenvironment cells, namely regulatory T cells. High BTLA expression in chimeric antigen receptor (CAR) T cells correlated with poor clinical response to treatment. Therefore, we deleted BTLA in CAR T cells and show improved tumor control and persistence in models of lymphoma and solid malignancies. Mechanistically, BTLA inhibits CAR T cells via recruitment of tyrosine phosphatases SHP-1 and SHP-2, upon trans engagement with HVEM. BTLA knockout thus promotes CAR signaling and subsequently enhances effector function. Overall, these data indicate that the BTLA-HVEM axis is a crucial immune checkpoint in CAR T cell immunotherapy and warrants the use of strategies to overcome this barrier.


Assuntos
Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Receptores Imunológicos , Membro 14 de Receptores do Fator de Necrose Tumoral , Microambiente Tumoral , Animais , Humanos , Imunoterapia Adotiva/métodos , Membro 14 de Receptores do Fator de Necrose Tumoral/metabolismo , Membro 14 de Receptores do Fator de Necrose Tumoral/imunologia , Membro 14 de Receptores do Fator de Necrose Tumoral/genética , Camundongos , Microambiente Tumoral/imunologia , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/genética , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Linfócitos T Reguladores/imunologia , Transdução de Sinais , Linhagem Celular Tumoral , Neoplasias/imunologia , Neoplasias/terapia , Camundongos Knockout
17.
ACS Appl Mater Interfaces ; 16(26): 33669-33687, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38912904

RESUMO

To learn more about the behavior of amine (NH2)-functionalized metal-organic framework (MOF)-derived noble metal catalysts in the removal of aromatic volatile organic compounds in air, benzene oxidation at low temperatures has been investigated using 0.2-, 0.8-, and 1.5%-platinum (Pt)/Universitetet i Oslo (UiO)-66-NH2. The benzene conversion (XB) of x%-Pt/UiO-66-NH2-R under dry conditions (175 °C) was 23% (x = 0.2%) < 52% (x = 0.8%) < 100% (x = 1.5%): 'R' suffix denotes reduction pretreatment using a hydrogen (10 vol %) and nitrogen mixture at 300 °C for the generation of metallic Pt (Pt0) sites and simultaneous partial MOF decomposition into carbon- and nitrogen-loaded zirconium dioxide. The prominent role of reduction pretreatment was apparent in benzene oxidation as 1.5%-Pt/UiO-66-NH2 did not exhibit catalytic activity below 175 °C (dry condition). The promotional role of moisture in benzene oxidation by 1.5%-Pt/UiO-66-NH2-R was evident with a rise in the steady-state reaction rate (r) at 110 °C (21 kPa molecular oxygen (O2)) from 1.3 × 10-3 to 5.0 × 10-3 µmol g-1 s-1 as the water (H2O) partial pressure increased from 0 to 1.88 kPa. In contrast, the activity was lowered with increasing RH due to catalyst poisoning by excess moisture (r (110 °C) of 6.6 × 10-04 µmol g-1 s-1 at 2.83 kPa H2O (21 kPa O2)). Kinetic modeling suggests that XB proceeds through the Langmuir-Hinshelwood mechanism on the Pt/UiO-66-NH2-R surface (dissociative O2 chemisorption and the involvement of two oxygen species in benzene oxidation). According to the density functional theory simulation, the carbon and nitrogen impurities are to make the first XB step (i.e., hydrogen migration from the benzene molecule to the substrate) energetically favorable. The second hydrogen atom from the benzene molecule is also extracted effectively, while the oxygen derived from O2 facilitates further XB. The Pt0 sites dissociate the O2 and H2O molecules, while the product of the latter, i.e., free hydrogen and hydroxyl, makes the subsequent XB steps energetically favorable.

18.
Mikrochim Acta ; 191(6): 324, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38730197

RESUMO

A robust "on-off" fluorescent aptasensor was developed using nanohybrids of molybdenum sulfide (MoS2) quantum dot (QD)-doped zinc metal-organic frameworks (Zn-MOF) for selective and sensitive detection of cadmium ions (Cd2+) in water. This nanohybrid (MoS2@Zn-MOF), synthesized via "bottle around the ship" methodology, exhibited a high-intensity fluorescence emission centered at 430 nm (λEm) (blue) on excitation at 320 nm (λEx). Further, the conjugation of this fluorophore to phosphate-modified cadmium aptamer (Cd-2-2) was achieved through carbodiimide reaction. The hybridization of prepared sensing probe (MoS2@Zn-MOF/Cd-2-2 aptamer) was done with dabcyl-conjugated complementary DNA (cDNA), acting as energy donor-acceptor pair in the fluorescence resonance energy transfer (FRET) system. This hybridization causes the fluorescence quenching of the nanohybrid. In the presence of Cd2+, the aptamer from the fabricated nano-biosensing probe binds to these ions, resulting in release of dabcyl-cDNA oligomer. This release of dabcyl-cDNA oligomer from the sensing probes restores the fluorescence of the nanohybrid. Under optimized conditions (sensing probe/dabcyl-cDNA ratio 1/7, pH 7.4, and temp 28 °C), the sensing probe showed a fast response time of 1 min. The fluorescence intensity of the nanohybrid can be utilized to determine the concentration of Cd2+. The proposed aptasensor achieved highly sensitive detection of Cd2+ with a limit of detection (LOD) of 0.24 ppb over the range of 1 × 10-9 to 1 × 10-4 M along with minimal effects of interferences (e.g., Hg2+, Pb2+, and Zn2+) and good reproducibility. The designed aptasensor based on MoS2@Zn-MOF nanofluorophore offers a highly sensitive and selective approach for rapid screening of metal ions in aqueous environments.

19.
Chemosphere ; 360: 142364, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38768790

RESUMO

In this work, the practical utility of constructed wetlands (CWs) is described as a promising treatment option for micropollutants (MPs) in wastewater with the aid of their eco-friendly, low-energy, economically feasible, and ecologically sustainable nature. This paper offers a comprehensive review on CW technology with respect to the key strategies for MP removal such as phytoremediation, substrate adsorption, and microbial degradation. It explores the important factors controlling the performance of CWs (e.g., in terms of configurations, substrates, plant-microbe interactions, temperature, pH, oxygen levels, hydraulic loading rate, and retention time) along with the discussions on the pivotal role of microbial populations in CWs and plant-microbe cooperative remediation dynamics, particularly in relation to diverse organic MP patterns in CWs. As such, this review aims to provide valuable insights into the key strategies for optimizing MP treatment and for enhancing the efficacy of CW systems. In addition, the process-based models of constructed wetlands along with the numerical simulations based on the artificial neural network (ANN) method are also described in association with the data exploratory techniques. This work is thus expected to help open up new possibilities for the application of plant-microbe cooperative remediation approaches against diverse patterns of organic MPs present in CWs.


Assuntos
Biodegradação Ambiental , Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água , Áreas Alagadas , Águas Residuárias/química , Poluentes Químicos da Água/análise , Eliminação de Resíduos Líquidos/métodos , Adsorção
20.
Sci Rep ; 14(1): 12353, 2024 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811758

RESUMO

A positive resection margin after colorectal endoscopic submucosal dissection (ESD) is associated with an increased risk of recurrence. We aimed to identify the clinical significance of positive resection margins in colorectal neoplasms after ESD. We reviewed 632 patients who had en bloc colorectal ESD at two hospitals between 2015 and 2020. The recurrence rates and presence of residual tumor after surgery were evaluated. The rate of additional surgery after ESD and recurrence rate were significantly higher in patients with incomplete resection (n = 75) compared to patients with complete resection (n = 557). When focusing solely on non-invasive lesions, no significant differences in recurrence rates were observed between the groups with complete and incomplete resection (0.2% vs. 1.9%, p = 0.057). Among 84 patients with submucosal invasive carcinoma, 39 patients underwent additional surgery due to non-curative resection. Positive vertical margin and lymphovascular invasion were associated with residual tumor. Lymphovascular invasion was associated with lymph node metastasis. However, no residual tumor nor lymph node metastases were found in patients with only one unfavorable histological factor. In conclusion, a positive resection margin in non-invasive colorectal lesions, did not significantly impact the recurrence rate. Also, in T1 colorectal cancer with a positive vertical resection margin, salvage surgery can be considered in selected patients with additional risk factors.


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Margens de Excisão , Recidiva Local de Neoplasia , Humanos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Masculino , Feminino , Ressecção Endoscópica de Mucosa/métodos , Idoso , Recidiva Local de Neoplasia/patologia , Pessoa de Meia-Idade , Neoplasia Residual/patologia , Resultado do Tratamento , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Metástase Linfática
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...