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1.
J Environ Manage ; 365: 121610, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38955048

RESUMO

Effective elimination of heavy metals from complex wastewater is of great significance for industrial wastewater treatment. Herein, bimetallic adsorbent Fe3O4-CeO2 was prepared, and H2O2 was added to enhance Sb(V) adsorption by Fe3O4-CeO2 in complex wastewater of Sb(V) and aniline aerofloat (AAF) for the first time. Fe3O4-CeO2 showed good adsorption performance and could be rapidly separated by external magnetic field. After five adsorption/desorption cycles, Fe3O4-CeO2 still maintained good stability. The maximum adsorption capacities of Fe3O4-CeO2 in single Sb(V), AAF + Sb(V), and H2O2+AAF + Sb(V) systems were 77.33, 70.14, and 80.59 mg/g, respectively. Coexisting AAF inhibited Sb(V) adsorption. Conversely, additional H2O2 promoted Sb(V) removal in AAF + Sb(V) binary system, and made the adsorption capacity of Fe3O4-CeO2 increase by 14.90%. H2O2 could not only accelerate the reaction rate, but also reduce the optimal amount of adsorbent from 2.0 g/L to 1.2 g/L. Meanwhile, coexisting anions had little effect on Sb(V) removal by Fe3O4-CeO2+H2O2 process. The adsorption behaviors of Sb(V) in three systems were better depicted by pseudo-second-order kinetics, implying that the chemisorption was dominant. The complexation of AAF with Sb(V) hindered the adsorption of Sb(V) by Fe3O4-CeO2. The complex Sb(V) was oxidized and decomposed into free state by hydroxyl radicals produced in Fe3O4-CeO2+H2O2 process. Then the free Sb(V) was adsorbed by Fe3O4-CeO2 mostly through outer-sphere complexation. This work provides a new tactic for the treatment of heavy metal-organics complex wastewater.


Assuntos
Peróxido de Hidrogênio , Águas Residuárias , Águas Residuárias/química , Peróxido de Hidrogênio/química , Adsorção , Poluentes Químicos da Água/química , Compostos de Anilina/química , Cério/química
2.
Chemistry ; : e202401553, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937940

RESUMO

Copper iodide organic-inorganic hybrid materials have been favored by many researchers in the field of solid-state lighting (SSL) due to their structural diversity and optical adjustability. In this paper, three isomeric copper iodide cluster hybrid materials, Cu4I6(L)2(1), Cu5I4.5Cl2.5(L)2(2) and Cu5I7(L)2) (3) (L=1-(4-methylpyrimidin-2-yl)-1,4-diazabicyclo[2.2.2]octan-1-ium), were achieved by adjusting the reaction conditions. The crystal color transit from green, yellow to orange and the internal quantum yield (IQY) increase from 57% to 88%. All three complexes have good thermal stability, good solution processability, and high quantum yield. And origin and mechanism of luminescence of complexes were further studied. This study can provide ideas and theoretical basis for the regulation of cuprous iodide cluster luminescent materials.

3.
FASEB J ; 38(13): e23751, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38923701

RESUMO

Mesenchymal stem cells (MSCs) reveal multifaceted immunoregulatory properties, which can be applied for diverse refractory and recurrent disease treatment including acute graft-versus-host disease (aGVHD). Distinguishing from MSCs with considerable challenges before clinical application, MSCs-derived exosomes (MSC-Exos) are cell-free microvesicles with therapeutic ingredients and serve as advantageous alternatives for ameliorating the outcomes of aGVHD. MSC-Exos were enriched and identified by western blotting analysis, NanoSight, and transmission electron microscopy (TEM). Bone marrow-derived MSCs (denoted as MSCs) and exosomes (denoted as MSC-Exos) were infused into the aGVHD SD-Wister rat model via tail vein, and variations in general growth and survival of rats were observed. The level of inflammatory factors in serum was quantized by enzyme-linked immunosorbent assay (ELISA). The pathological conditions of the liver and intestine of rats were observed by frozen sectioning. The ratios of CD4+/CD8+ and Treg cell proportions in peripheral blood, together with the autophagy in the spleen and thymus, were analyzed by flow cytometry. After treatment with MSC-Exos, the survival time of aGVHD rats was prolonged, the clinical manifestations of aGVHD in rats were improved, whereas the pathological damage of aGVHD in the liver and intestine was reduced. According to ELISA, we found that MSC-Exos revealed ameliorative effect upon aGVHD inflammation (e.g., TNF-α, IL-2, INF-γ, IL-4, and TGF-ß) compared to the MSC group. After MSC-Exo treatment, the ratio of Treg cells in peripheral blood was increased, whereas the ratio of CD4+/CD8+ in peripheral blood and the autophagy in the spleen and thymus was decreased. MSC-Exos effectively suppressed the activation of immune cells and the manifestation of the inflammatory response in the aGVHD rat model. Our data would supply new references for MSC-Exo-based "cell-free" biotherapy for aGVHD in future.


Assuntos
Exossomos , Doença Enxerto-Hospedeiro , Células-Tronco Mesenquimais , Animais , Exossomos/metabolismo , Doença Enxerto-Hospedeiro/terapia , Ratos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Ratos Wistar , Masculino , Ratos Sprague-Dawley , Transplante de Células-Tronco Mesenquimais/métodos , Linfócitos T Reguladores/imunologia , Células da Medula Óssea/citologia , Autofagia
4.
J Exp Clin Cancer Res ; 43(1): 163, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38863037

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and lack of effective targets, it is crucial to identify novel molecular targets that would increase RT efficacy. Here we demonstrate the role of BUB1 (cell cycle Ser/Thr kinase) in TNBC radioresistance and offer a novel strategy to improve TNBC treatment. METHODS: Gene expression analysis was performed to look at genes upregulated in TNBC patient samples compared to other subtypes. Cell proliferation and clonogenic survivals assays determined the IC50 of BUB1 inhibitor (BAY1816032) and radiation enhancement ratio (rER) with pharmacologic and genomic BUB1 inhibition. Mammary fat pad xenografts experiments were performed in CB17/SCID. The mechanism through which BUB1 inhibitor sensitizes TNBC cells to radiotherapy was delineated by γ-H2AX foci assays, BLRR, Immunoblotting, qPCR, CHX chase, and cell fractionation assays. RESULTS: BUB1 is overexpressed in BC and its expression is considerably elevated in TNBC with poor survival outcomes. Pharmacological or genomic ablation of BUB1 sensitized multiple TNBC cell lines to cell killing by radiation, although breast epithelial cells showed no radiosensitization with BUB1 inhibition. Kinase function of BUB1 is mainly accountable for this radiosensitization phenotype. BUB1 ablation also led to radiosensitization in TNBC tumor xenografts with significantly increased tumor growth delay and overall survival. Mechanistically, BUB1 ablation inhibited the repair of radiation-induced DNA double strand breaks (DSBs). BUB1 ablation stabilized phospho-DNAPKcs (S2056) following RT such that half-lives could not be estimated. In contrast, RT alone caused BUB1 stabilization, but pre-treatment with BUB1 inhibitor prevented stabilization (t1/2, ~8 h). Nuclear and chromatin-enriched fractionations illustrated an increase in recruitment of phospho- and total-DNAPK, and KAP1 to chromatin indicating that BUB1 is indispensable in the activation and recruitment of non-homologous end joining (NHEJ) proteins to DSBs. Additionally, BUB1 staining of TNBC tissue microarrays demonstrated significant correlation of BUB1 protein expression with tumor grade. CONCLUSIONS: BUB1 ablation sensitizes TNBC cell lines and xenografts to RT and BUB1 mediated radiosensitization may occur through NHEJ. Together, these results highlight BUB1 as a novel molecular target for radiosensitization in women with TNBC.


Assuntos
Reparo do DNA por Junção de Extremidades , Proteínas Serina-Treonina Quinases , Tolerância a Radiação , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/radioterapia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Animais , Feminino , Camundongos , Linhagem Celular Tumoral , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Camundongos SCID
5.
Nano Lett ; 24(27): 8343-8350, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38923939

RESUMO

The shrinkage and collapse of wood cell walls during carbonization make it challenging to control the size and shape of carbonized wood (CW) through pre- or postprocessing (e.g., sawing, cutting, and milling). Herein, a shape-adaptive MXene shell (MS) is created on the surface of the wood cell walls. The MS limits the deformation of wood cell walls by spatial confinement and traction effects, which is supported by the inherent dimensional stability of the MS and the formation of new C-O-Ti covalent bonds between the wood cell wall and MS. Consequently, the volumetric shrinkage ratio of CW encapsulated by the MS (CW-MS) is significantly reduced from 54.8% for CW to 2.6% for CW-MS even at 800 °C. The harnessing of this collapse enables the production of CW-MS with prolonged stability and high electric conductivity (384 S m-1). These properties make CW-MS suitable for energy storage devices with various designed shapes, matching the increasingly compact and complex structures of electronic devices.

6.
PLoS One ; 19(5): e0297137, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38722851

RESUMO

BACKGROUND: Inhaled nitric oxide (iNO) has a beneficial effect on hypoxemic respiratory failure. The increased use of concurrent iNO and milrinone was observed. We aimed to report the trends of iNO use in the past 15 years in Taiwan and compare the first-year outcomes of combining iNO and milrinone to the iNO alone in very low birth weight preterm (VLBWP) infants under mechanical ventilation. METHODS: This nationwide cohort study enrolled preterm singleton infants with birth weight <1500g treated with iNO from 2004 to 2019. Infants were divided into two groups, with a combination of intravenous milrinone (Group 2, n = 166) and without milrinone (Group 1, n = 591). After propensity score matching (PSM), each group's sample size is 124. The primary outcomes were all-cause mortality and the respiratory condition, including ventilator use and duration. The secondary outcomes were preterm morbidities within one year after birth. RESULTS: After PSM, more infants in Group 2 needed inotropes. The mortality rate was significantly higher in Group 2 than in Group 1 from one month after birth till 1 year of age (55.1% vs. 13.5%) with the adjusted hazard ratio of 4.25 (95%CI = 2.42-7.47, p <0.001). For infants who died before 36 weeks of postmenstrual age (PMA), Group 2 had longer hospital stays compared to Group 1. For infants who survived after 36 weeks PMA, the incidence of moderate and severe bronchopulmonary dysplasia (BPD) was significantly higher in Group 2 than in Group 1. For infants who survived until one year of age, the incidence of pneumonia was significantly higher in Group 2 (28.30%) compared to Group 1 (12.62%) (p = 0.0153). CONCLUSION: Combined treatment of iNO and milrinone is increasingly applied in VLBWP infants in Taiwan. This retrospective study did not support the benefits of combining iNO and milrinone on one-year survival and BPD prevention. A future prospective study is warranted.


Assuntos
Recém-Nascido de muito Baixo Peso , Milrinona , Óxido Nítrico , Humanos , Milrinona/administração & dosagem , Milrinona/uso terapêutico , Recém-Nascido , Óxido Nítrico/administração & dosagem , Óxido Nítrico/uso terapêutico , Masculino , Administração por Inalação , Feminino , Estudos Retrospectivos , Taiwan/epidemiologia , Recém-Nascido Prematuro , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/mortalidade , Lactente , Respiração Artificial , Resultado do Tratamento , Hipóxia/tratamento farmacológico
7.
Nano Lett ; 24(22): 6576-6584, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38775216

RESUMO

Hierarchical biobased micro/nanomaterials offer great potential as the next-generation building blocks for robust films or macroscopic fibers with high strength, while their capability in suppressing crack propagation when subject to damage is hindered by their limited length. Herein, we employed an approach to directly convert bulk wood into fibers with a high aspect ratio and nanosized branching structures. Particularly, the length of microfibers surpassed 1 mm with that of the nanosized branches reaching up to 300 µm. The presence of both interwoven micro- and nanofibers endowed the product with substantially improved tensile strength (393.99 MPa) and toughness (19.07 MJ m-3). The unique mechanical properties arose from mutual filling and the hierarchical deformation facilitated by branched nanofibers, which collectively contributed to effective energy dissipation. Hence, the nanotransformation strategy opens the door toward a facial, scalable method for building high-strength film or macroscopic fibers available in various advanced applications.

8.
ACS Infect Dis ; 10(6): 2303-2317, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38725130

RESUMO

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1H)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo. By monitoring changes in the fluorescence intensity of FAM conjugate 20 in bacteria, the translocation of the conjugate across the outer membranes of Gram-negative pathogens was confirmed. Further, the use of the fluorogen activating protein(FAP)/MG system revealed that 3-hydroxypyridin-4(1H)-one-MG conjugate 26 was ultimately distributed mainly in the periplasm rather than being translocated into the cytosol of Escherichia coli and Pseudomonas aeruginosa PAO1. Additional mechanistic studies suggested that the uptake of the conjugate involved the siderophore-dependent iron transport pathway and the 3-hydroxypyridin-4(1H)-ones siderophore receptor-dependent mechanism. Meanwhile, we demonstrated that the conjugation of 3-hydroxypyridin-4(1H)-ones to the fluorescein 5-FAM can reduce the possibility of the conjugates crossing the membrane layers of mammalian Vero cells by passive diffusion, and the advantages of the mono-3-hydroxypyridin-4(1H)-ones as a delivery vehicle in the design of conjugates compared to the tri-3-hydroxypyridin-4(1H)-ones. Overall, this work reveals the localization rules of 3-hydroxypyridin-4(1H)-ones as siderophores to deliver the cargo into Gram-negative bacteria. It provides a theoretical basis for the subsequent design of siderophore-antibiotic conjugates, especially based on 3-hydroxypyridin-4(1H)-ones as siderophores.


Assuntos
Antibacterianos , Pseudomonas aeruginosa , Sideróforos , Sideróforos/química , Sideróforos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Corantes Fluorescentes/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Piridonas/farmacologia , Piridonas/química , Piridinas/química , Piridinas/farmacologia , Animais , Fluoresceína/química , Transporte Biológico , Testes de Sensibilidade Microbiana
9.
bioRxiv ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38766122

RESUMO

Background: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and lack of effective targets, it is crucial to identify novel molecular targets that would increase RT efficacy. Here we demonstrate the role of BUB1 (cell cycle Ser/Thr kinase) in TNBC radioresistance and offer a novel strategy to improve TNBC treatment. Methods: Gene expression analysis was performed to look at genes upregulated in TNBC patient samples compared to other subtypes. Cell proliferation and clonogenic survivals assays determined the IC 50 of BUB1 inhibitor (BAY1816032) and radiation enhancement ratio (rER) with pharmacologic and genomic BUB1 inhibition. Mammary fat pad xenografts experiments were performed in CB17/SCID. The mechanism through which BUB1 inhibitor sensitizes TNBC cells to radiotherapy was delineated by γ-H2AX foci assays, BLRR, Immunoblotting, qPCR, CHX chase, and cell fractionation assays. Results: BUB1 is overexpressed in BC and its expression is considerably elevated in TNBC with poor survival outcomes. Pharmacological or genomic ablation of BUB1 sensitized multiple TNBC cell lines to cell killing by radiation, although breast epithelial cells showed no radiosensitization with BUB1 inhibition. Kinase function of BUB1 is mainly accountable for this radiosensitization phenotype. BUB1 ablation also led to radiosensitization in TNBC tumor xenografts with significantly increased tumor growth delay and overall survival. Mechanistically, BUB1 ablation inhibited the repair of radiation-induced DNA double strand breaks (DSBs). BUB1 ablation stabilized phospho-DNAPKcs (S2056) following RT such that half-lives could not be estimated. In contrast, RT alone caused BUB1 stabilization, but pre-treatment with BUB1 inhibitor prevented stabilization (t 1/2 , ∼8 h). Nuclear and chromatin-enriched fractionations illustrated an increase in recruitment of phospho- and total-DNAPK, and KAP1 to chromatin indicating that BUB1 is indispensable in the activation and recruitment of non-homologous end joining (NHEJ) proteins to DSBs. Additionally, BUB1 staining of TNBC tissue microarrays demonstrated significant correlation of BUB1 protein expression with tumor grade. Conclusions: BUB1 ablation sensitizes TNBC cell lines and xenografts to RT and BUB1 mediated radiosensitization may occur through NHEJ. Together, these results highlight BUB1 as a novel molecular target for radiosensitization in women with TNBC.

10.
Medicine (Baltimore) ; 103(16): e37901, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640266

RESUMO

Taiwan is one of the countries with the highest motorcycle per capita globally, and motorcycle crashes are predominant among traffic crashes. This study examines the impact of coronavirus disease 2019 restrictions on motorcycle crashes. We analyzed the trend of motorcycle crashes in Taipei City from 2019 to 2020 using the dataset provided by the Department of Transportation, Taipei City Government, Taiwan. We found 47,108 and 51,441 motorcycle crashes in 2019 and 2020, involving 61,141 and 67,093 motorcycles, respectively. Mopeds had the highest risk in 2020, followed by heavy motorcycles [≥550 cubic capacity (cc)] and scooters compared to 2019. Food delivery motorcycle crashes increased for scooters (0.93% in 2019 to 3.45% in 2020, P < .0001) and heavy motorcycles (250 < cc < 550) (0.90% in 2019 to 3.38% in 2020, P < .0001). While fatalities remained under 1%, 30% to 51% of motorcyclists sustained injuries. Food delivery with scooters or heavy motorcycles (250 < cc < 550) was significantly associated with motorcyclist injuries and deaths. Compared with 2019, the adjusted odds ratios of motorcyclist injuries and deaths in 2020 were 1.43 (95% confidence interval = 1.05-1.94) for heavy motorcycles (≥550 cc) and 1.07 (95% confidence interval = 1.04-1.09) for scooters. This study shows that coronavirus disease 2019 restrictions was associated with elevated risks of crashes, injuries, and deaths among motorcyclists, reflecting the general preference for private transport over public transport. The popularity of food delivery services also contributed to increased motorcycle crashes.


Assuntos
Acidentes de Trânsito , COVID-19 , Humanos , Motocicletas , Taiwan/epidemiologia , COVID-19/epidemiologia
11.
J Phys Chem C Nanomater Interfaces ; 128(12): 5313-5320, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38567374

RESUMO

Solution-processable semiconductors with antiferromagnetic (AFM) order are attractive for future spintronics and information storage technology. Halide perovskites containing magnetic ions have emerged as multifunctional materials, demonstrating a cross-link between structural, optical, electrical, and magnetic properties. However, stable optoelectronic halide perovskites that are antiferromagnetic remain sparse, and the critical design rules to optimize magnetic coupling still must be developed. Here, we combine the complementary magnetometry and electron-spin-resonance experiments, together with first-principles calculations to study the antiferromagnetic coupling in stable Cs2(Ag:Na)FeCl6 bulk semiconductor alloys grown by the hydrothermal method. We show the importance of nonmagnetic monovalence ions at the BI site (Na/Ag) in facilitating the superexchange interaction via orbital hybridization, offering the tunability of the Curie-Weiss parameters between -27 and -210 K, with a potential to promote magnetic frustration via alloying the nonmagnetic BI site (Ag:Na ratio). Combining our experimental evidence with first-principles calculations, we draw a cohesive picture of the material design for B-site-ordered antiferromagnetic halide double perovskites.

12.
Hum Mol Genet ; 33(11): 958-968, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38453145

RESUMO

Type 1 diabetes (T1D) is an autoimmune disease caused by destruction of the pancreatic ß-cells. Genome-wide association (GWAS) and fine mapping studies have been conducted mainly in European ancestry (EUR) populations. We performed a multi-ancestry GWAS to identify SNPs and HLA alleles associated with T1D risk and age at onset. EUR families (N = 3223), and unrelated individuals of African (AFR, N = 891) and admixed (Hispanic/Latino) ancestry (AMR, N = 308) were genotyped using the Illumina HumanCoreExome BeadArray, with imputation to the TOPMed reference panel. The Multi-Ethnic HLA reference panel was utilized to impute HLA alleles and amino acid residues. Logistic mixed models (T1D risk) and frailty models (age at onset) were used for analysis. In GWAS meta-analysis, seven loci were associated with T1D risk at genome-wide significance: PTPN22, HLA-DQA1, IL2RA, RNLS, INS, IKZF4-RPS26-ERBB3, and SH2B3, with four associated with T1D age at onset (PTPN22, HLA-DQB1, INS, and ERBB3). AFR and AMR meta-analysis revealed NRP1 as associated with T1D risk and age at onset, although NRP1 variants were not associated in EUR ancestry. In contrast, the PTPN22 variant was significantly associated with risk only in EUR ancestry. HLA alleles and haplotypes most significantly associated with T1D risk in AFR and AMR ancestry differed from that seen in EUR ancestry; in addition, the HLA-DRB1*08:02-DQA1*04:01-DQB1*04:02 haplotype was 'protective' in AMR while HLA-DRB1*08:01-DQA1*04:01-DQB1*04:02 haplotype was 'risk' in EUR ancestry, differing only at HLA-DRB1*08. These results suggest that much larger sample sizes in non-EUR populations are required to capture novel loci associated with T1D risk.


Assuntos
Diabetes Mellitus Tipo 1 , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Humanos , Diabetes Mellitus Tipo 1/genética , Masculino , Feminino , População Branca/genética , Idade de Início , Alelos , Cadeias alfa de HLA-DQ/genética , População Negra/genética , Criança , Hispânico ou Latino/genética , Antígenos HLA/genética , Adolescente
13.
Eur J Med Chem ; 269: 116339, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38537513

RESUMO

The low permeability of the outer membrane of Gram-negative bacteria is a serious obstacle to the development of new antibiotics against them. Conjugation of antibiotic with siderophore based on the "Trojan horse strategy" is a promising strategy to overcome the outer membrane obstacle. In this study, series of antibacterial agents were designed and synthesized by conjugating the 3-hydroxypyridin-4(1H)-one based siderophores with cajaninstilbene acid (CSA) derivative 4 which shows good activity against Gram-positive bacteria by targeting their cell membranes but is ineffective against Gram-negative bacteria. Compared to the inactive parent compound 4, the conjugates 45c or 45d exhibits significant improvement in activity against Gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae and especially P. aeruginosa (minimum inhibitory concentrations, MICs = 7.8-31.25 µM). The antibacterial activity of the conjugates is attributed to the CSA derivative moiety, and the action mechanism is by disruption of bacterial cell membranes. Further studies on the uptake mechanisms showed that the bacterial siderophore-dependent iron transport system was involved in the uptake of the conjugates. In addition, the conjugates 45c and 45d showed a lower cytotoxic effects in vivo and in vitro and a positive therapeutic effect in the treatment of C. elegans infected by P. aeruginosa. Overall, our work describes a new class and a promising 3-hydroxypyridin-4(1H)-one-CSA derivative conjugates for further development as antibacterial agents against Gram-negative bacteria.


Assuntos
Antibacterianos , Salicilatos , Sideróforos , Estilbenos , Animais , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Sideróforos/farmacologia , Sideróforos/metabolismo , Caenorhabditis elegans/metabolismo , Bactérias Gram-Negativas , Bactérias/metabolismo , Testes de Sensibilidade Microbiana
14.
Environ Res ; 250: 118518, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38382662

RESUMO

Plant residues are important sources of soil organic carbon in terrestrial ecosystems. The degradation of plant residue by microbes can influence the soil carbon cycle and sequestration. However, little is known about the microbial composition and function, as well as the accumulation of soil organic carbon (SOC) in response to the inputs of different quality plant residues in the desert environment. The present study evaluated the effects of plant residue addition from Pinus sylvestris var. mongolica (Pi), Artemisia desertorum (Ar) and Amorpha fruticosa (Am) on desert soil microbial community composition and function in a field experiment in the Mu Us Desert. The results showed that the addition of the three plant residues with different C/N ratios induced significant variation in soil microbial communities. The Am treatment (low C/N ratio) improved microbial diversity compared with the Ar and Pi treatments (medium and high C/N ratios). The variations in the taxonomic and functional compositions of the dominant phyla Actinobacteria and Proteobacteria were higher than those of the other phyla among the different treatments. Moreover, the network links between Proteobacteria and other phyla and the CAZyme genes abundances from Proteobacteria increased with increasing residue C/N, whereas those decreased for Actinobacteria. The SOC content of the Am, Ar and Pi treatments increased by 45.73%, 66.54% and 107.99%, respectively, as compared to the original soil. The net SOC accumulation was positively correlated with Proteobacteria abundance and negatively correlated with Actinobacteria abundance. These findings showed that changing the initial quality of plant residue from low C/N to high C/N can result in shifts in taxonomic and functional composition from Actinobacteria to Proteobacteria, which favors SOC accumulation. This study elucidates the ecophysiological roles of Actinobacteria and Proteobacteria in the desert carbon cycle, expands our understanding of the potential microbial-mediated mechanisms by which plant residue inputs affect SOC sequestration in desert soils, and provides valuable guidance for species selection in desert vegetation reconstruction.


Assuntos
Clima Desértico , Microbiologia do Solo , Ecossistema , Carbono/análise , Carbono/metabolismo , Solo/química , Sequestro de Carbono , Microbiota , Bactérias/classificação , Bactérias/genética
15.
Genome Med ; 16(1): 31, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355597

RESUMO

BACKGROUND: Population screening for risk of type 1 diabetes (T1D) has been proposed to identify those with islet autoimmunity (presence of islet autoantibodies). As islet autoantibodies can be transient, screening with a genetic risk score has been proposed as an entry into autoantibody testing. METHODS: Children were recruited from eight general pediatric and specialty clinics across Virginia with diverse community settings. Recruiters in each clinic obtained informed consent/assent, a medical history, and a saliva sample for DNA extraction in children with and without a history of T1D. A custom genotyping panel was used to define T1D genetic risk based upon associated SNPs in European- and African-genetic ancestry. Subjects at "high genetic risk" were offered a separate blood collection for screening four islet autoantibodies. A follow-up contact (email, mail, and telephone) in one half of the participants determined interest and occurrence of subsequent T1D. RESULTS: A total of 3818 children aged 2-16 years were recruited, with 14.2% (n = 542) having a "high genetic risk." Of children with "high genetic risk" and without pre-existing T1D (n = 494), 7.0% (34/494) consented for autoantibody screening; 82.4% (28/34) who consented also completed the blood collection, and 7.1% (2/28) of them tested positive for multiple autoantibodies. Among children with pre-existing T1D (n = 91), 52% (n = 48) had a "high genetic risk." In the sample of children with existing T1D, there was no relationship between genetic risk and age at T1D onset. A major factor in obtaining islet autoantibody testing was concern over SARS-CoV-2 exposure. CONCLUSIONS: Minimally invasive saliva sampling implemented using a genetic risk score can identify children at genetic risk of T1D. Consent for autoantibody screening, however, was limited largely due to the SARS-CoV-2 pandemic and need for blood collection.


Assuntos
Diabetes Mellitus Tipo 1 , Criança , Humanos , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Virginia , Fatores de Risco , Autoanticorpos/genética , Autoimunidade/genética , Estratificação de Risco Genético
16.
Int J Mol Sci ; 25(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38397002

RESUMO

Ferroptosis, a unique form of programmed cell death trigged by lipid peroxidation and iron accumulation, has been implicated in embryonic erythropoiesis and aging. Our previous research demonstrated that lysophosphatidic acid receptor 3 (LPA3) activation mitigated oxidative stress in progeria cells and accelerated the recovery of acute anemia in mice. Given that both processes involve iron metabolism, we hypothesized that LPA3 activation might mediate cellular ferroptosis. In this study, we used an LPA3 agonist, 1-Oleoyl-2-O-methyl-rac-glycerophosphothionate (OMPT), to activate LPA3 and examine its effects on the ferroptosis process. OMPT treatment elevated anti-ferroptosis gene protein expression, including solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), heme oxygenase-1 (HO-1), and ferritin heavy chain (FTH1), in erastin-induced cells. Furthermore, OMPT reduced lipid peroxidation and intracellular ferrous iron accumulation, as evidenced by C11 BODIPY™ 581/591 Lipid Peroxidation Sensor and FerroOrange staining. These observations were validated by applying LPAR3 siRNA in the experiments mentioned above. In addition, the protein expression level of nuclear factor erythroid 2-related factor (NRF2), a key regulator of oxidative stress, was also enhanced in OMPT-treated cells. Lastly, we verified that LPA3 plays a critical role in erastin-induced ferroptotic human erythroleukemia K562 cells. OMPT rescued the erythropoiesis defect caused by erastin in K562 cells based on a Gly A promoter luciferase assay. Taken together, our findings suggest that LPA3 activation inhibits cell ferroptosis by suppressing lipid oxidation and iron accumulation, indicating that ferroptosis could potentially serve as a link among LPA3, erythropoiesis, and aging.


Assuntos
Ferroptose , Receptores de Ácidos Lisofosfatídicos , Camundongos , Animais , Humanos , Receptores de Ácidos Lisofosfatídicos/genética , Receptores de Ácidos Lisofosfatídicos/metabolismo , Apoptose , Estresse Oxidativo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Ferro/metabolismo
17.
ACS Nano ; 18(2): 1477-1484, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38166147

RESUMO

In this study, we report a significant enhancement in the performance of GaNAs-based single nanowire lasers through optimization of growth conditions, leading to a lower lasing threshold and higher operation temperatures. Our analysis reveals that these improvements in the laser performance can be attributed to a decrease in the density of localized states within the material. Furthermore, we demonstrate that owing to their excellent nonlinear optical properties, these nanowires support self-frequency conversion of the stimulated emission through second harmonic generation (SHG) and sum-frequency generation (SFG), providing coherent light emission in the cyan-green range. Mode-specific differences in the self-conversion efficiency are revealed and explained by differences in the light extraction efficiency of the converted light caused by the electric field distribution of the fundamental modes. Our work, therefore, facilitates the design and development of multiwavelength coherent light generation and higher-temperature operation of GaNAs nanowire lasers, which will be useful in the fields of optical communications, sensing, and nanophotonics.

18.
Angew Chem Int Ed Engl ; 63(9): e202318063, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38190839

RESUMO

The aqueous zinc-ion battery is promising as grid scale energy storage device, but hindered by the instable electrode/electrolyte interface. Herein, we report the lean-water ionic liquid electrolyte for aqueous zinc metal batteries. The lean-water ionic liquid electrolyte creates the hydrophobic tri-layer interface assembled by first two layers of hydrophobic OTF- and EMIM+ and third layer of loosely attached water, beyond the classical Gouy-Chapman-Stern theory based electrochemical double layer. By taking advantage of the hydrophobic tri-layer interface, the lean-water ionic liquid electrolyte enables a wide electrochemical working window (2.93 V) with relatively high zinc ion conductivity (17.3 mS/cm). Furthermore, the anion crowding interface facilitates the OTF- decomposition chemistry to create the mechanically graded solid electrolyte interface layer to simultaneously suppress the dendrite formation and maintain the mechanical stability. In this way, the lean-water based ionic liquid electrolyte realizes the ultralong cyclability of over 10000 cycles at 20 A/g and at practical condition of N/P ratio of 1.5, the cumulated areal capacity reach 1.8 Ah/cm2 , which outperforms the state-of-the-art zinc metal battery performance. Our work highlights the importance of the stable electrode/electrolyte interface stability, which would be practical for building high energy grid scale zinc-ion battery.

19.
Am J Ophthalmol ; 258: 99-109, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37453473

RESUMO

PURPOSE: To estimate the familial risks of primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) and assess the relative contributions of environmental and genetic factors to these risks. DESIGN: Retrospective, population-based cohort study. METHODS: We used the 2000-2017 Taiwan National Health Insurance Program database to construct 4,144,508 families for the 2017 population (N = 23,373,209). We used the polygenic liability model to estimate glaucoma's heritability and familial transmission. The degree of familial aggregation of glaucoma was obtained from the adjusted relative risk for individuals whose first-degree relatives had glaucoma using Cox's model. RESULTS: PACG and POAG prevalence rates for individuals whose first-degree relatives had PACG or POAG were 0.95% and 2.40%, higher than those of the general population (0.61% and 0.40%, respectively). The relative risk of PACG in individuals whose first-degree relatives had PACG was 2.44 (95% CI = 2.31-2.58). The relative risk of POAG in individuals whose first-degree relatives had POAG was 6.66 (95% CI = 6.38-6.94). The estimated contributions to PACG and POAG phenotypic variances were 19.4% and 59.6% for additive genetic variance, 19.1% and 23.2% for common environmental factors shared by family members, and 61.5% and 17.2% for nonshared environmental factors, respectively. CONCLUSIONS: These data highlight the relative importance of genetic contribution to POAG and environmental contribution to PACG. Therefore, future work may need to focus on finding more novel environmental determinants of PACG.


Assuntos
Glaucoma de Ângulo Fechado , Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Glaucoma de Ângulo Aberto/epidemiologia , Glaucoma de Ângulo Aberto/genética , Estudos Retrospectivos , Glaucoma de Ângulo Fechado/epidemiologia , Glaucoma de Ângulo Fechado/genética , Taiwan/epidemiologia , Estudos de Coortes , Pressão Intraocular
20.
Adv Sci (Weinh) ; 11(4): e2306391, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38044299

RESUMO

Reversible optical property changes in lead-free perovskites have recently received great interest due to their potential applications in smart windows, sensors, data encryption, and various on-demand devices. However, it is challenging to achieve remarkable color changes in their thin films. Here, methylamine gas (CH3 NH2 , MA0 ) induced switchable optical bleaching of bismuth (Bi)-based perovskite films is demonstrated for the first time. By exposure to an MA0 atmosphere, the color of Cs2 AgBiBr6 (CABB) films changes from yellow to transparent, and the color of Cs3 Bi2 I9 (CBI) films changes from dark red to transparent. More interestingly, the underlying reason is found to be the interactions between MA0 and Bi3+ with the formation of an amorphous liquefied transparent intermediate phase, which is different from that of lead-based perovskite systems. Moreover, the generality of this approach is demonstrated with other amine gases, including ethylamine (C2 H5 NH2 , EA0 ) and butylamine (CH3 (CH2 )3 NH2 , BA0 ), and another compound, Cs3 Sb2 I9 , by observing a similar reversible optical bleaching phenomenon. The potential for the application of CABB and CBI films in switchable smart windows is investigated. This study provides valuable insights into the interactions between amine gases and lead-free perovskites, opening up new possibilities for high-efficiency optoelectronic and stimuli-responsive applications of these emerging Bi-based materials.

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