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1.
Plant Cell ; 35(11): 4002-4019, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37648256

RESUMO

Heading date (flowering time), which greatly influences regional and seasonal adaptability in rice (Oryza sativa), is regulated by many genes in different photoperiod pathways. Here, we characterized a heading date gene, Early heading date 5 (Ehd5), using a modified bulked segregant analysis method. The ehd5 mutant showed late flowering under both short-day and long-day conditions, as well as reduced yield, compared to the wild type. Ehd5, which encodes a WD40 domain-containing protein, is induced by light and follows a circadian rhythm expression pattern. Transcriptome analysis revealed that Ehd5 acts upstream of the flowering genes Early heading date 1 (Ehd1), RICE FLOWERING LOCUS T 1 (RFT1), and Heading date 3a (Hd3a). Functional analysis showed that Ehd5 directly interacts with Rice outermost cell-specific gene 4 (Roc4) and Grain number, plant height, and heading date 8 (Ghd8), which might affect the formation of Ghd7-Ghd8 complexes, resulting in increased expression of Ehd1, Hd3a, and RFT1. In a nutshell, these results demonstrate that Ehd5 functions as a positive regulator of rice flowering and provide insight into the molecular mechanisms underlying heading date.


Assuntos
Flores , Oryza , Ritmo Circadiano , Flores/genética , Flores/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Oryza/genética , Oryza/metabolismo , Fotoperíodo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Repetições WD40/genética
2.
Cereb Cortex ; 34(1)2024 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-38012118

RESUMO

The present study aimed to clarify the brain function of classical trigeminal neuralgia (CTN) by analyzing 77 CTN patients and age- and gender-matched 73 healthy controls (HCs) based on three frequency bands of the static and dynamic amplitude of low-frequency fluctuation, regional homogeneity, and degree centrality (sALFF, sReHo, sDC, dALFF, dReHo, and dDC). Compared to HCs, the number of altered brain regions was different in three frequency bands, and the classical frequency band was most followed by slow-4 in CTN patients. Cerrelellum_8_L (sReHo), Cerrelellum_8_R (sDC), Calcarine_R (sDC), and Caudate_R (sDC) were found only in classical frequency band, while Precuneus_L (sALFF) and Frontal_Inf_Tri_L (sReHo) were found only in slow-4 frequency band. Except for the above six brain regions, the others overlapped in the classical and slow-4 frequency bands. CTN seriously affects the mental health of patients, and some different brain regions are correlated with clinical parameters. The static and dynamic indicators of brain function were complementary in CTN patients, and the changing brain regions showed frequency specificity. Compared to slow-5 frequency band, slow-4 is more consistent with the classical frequency band, which could be valuable in exploring the pathophysiology of CTN.


Assuntos
Fenômenos Fisiológicos do Sistema Nervoso , Neuralgia do Trigêmeo , Humanos , Lobo Parietal , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética
3.
Nano Lett ; 24(19): 5791-5798, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38695400

RESUMO

The second-order nonlinear transport illuminates a frequency-doubling response emerging in quantum materials with a broken inversion symmetry. The two principal driving mechanisms, the Berry curvature dipole and the skew scattering, reflect various information including ground-state symmetries, band dispersions, and topology of electronic wave functions. However, effective manipulation of them in a single system has been lacking, hindering the pursuit of strong responses. Here, we report on the effective manipulation of the two mechanisms in a single graphene moiré superlattice, AB-BA stacked twisted double bilayer graphene. Most saliently, by virtue of the high tunability of moiré band structures and scattering rates, a record-high second-order transverse conductivity ∼ 510 µm S V-1 is observed, which is orders of magnitude higher than any reported values in the literature. Our findings establish the potential of electrically tunable graphene moiré systems for nonlinear transport manipulations and applications.

4.
Diabetologia ; 67(7): 1429-1443, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38676722

RESUMO

AIMS: Lactate accumulation is reported to be a biomarker for diabetic nephropathy progression. Lactate drives lysine lactylation, a newly discovered post-translational modification that is involved in the pathogenesis of cancers and metabolic and inflammatory disease. Here, we aimed to determine whether lysine lactylation is involved in the pathogenesis of diabetic nephropathy. METHODS: Renal biopsy samples from individuals with diabetic nephropathy (n=22) and control samples from individuals without diabetes and kidney disease (n=9) were obtained from the First Affiliated Hospital of Zhengzhou University for immunohistochemical staining. In addition, we carried out global lactylome profiling of kidney tissues from db/m and db/db mice using LC-MS/MS. Furthermore, we assessed the role of lysine lactylation and acyl-CoA synthetase family member 2 (ACSF2) in mitochondrial function in human proximal tubular epithelial cells (HK-2). RESULTS: The expression level of lysine lactylation was significantly increased in the kidneys of individuals with diabetes as well as in kidneys from db/db mice. Integrative lactylome analysis of the kidneys of db/db and db/m mice identified 165 upregulated proteins and 17 downregulated proteins, with an increase in 356 lysine lactylation sites and a decrease in 22 lysine lactylation sites decreased. Subcellular localisation analysis revealed that most lactylated proteins were found in the mitochondria (115 proteins, 269 sites). We further found that lactylation of the K182 site in ACSF2 contributes to mitochondrial dysfunction. Finally, the expression of ACSF2 was notably increased in the kidneys of db/db mice and individuals with diabetic nephropathy. CONCLUSIONS: Our study strongly suggests that lysine lactylation and ACSF2 are mediators of mitochondrial dysfunction and may contribute to the progression of diabetic nephropathy. DATA AVAILABILITY: The LC-MS/MS proteomics data have been deposited in the ProteomeXchange Consortium database ( https://proteomecentral.proteomexchange.org ) via the iProX partner repository with the dataset identifier PXD050070.


Assuntos
Nefropatias Diabéticas , Túbulos Renais , Lisina , Animais , Camundongos , Humanos , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Lisina/metabolismo , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Masculino , Coenzima A Ligases/metabolismo , Processamento de Proteína Pós-Traducional , Lipoilação , Camundongos Endogâmicos C57BL , Feminino
5.
Am J Epidemiol ; 193(2): 296-307, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-37814392

RESUMO

Body mass index (BMI; weight (kg)/height (m)2) is commonly used to measure general adiposity. However, evidence of its appropriateness for males and females remains inconsistent. We aimed to identify the most appropriate sex-specific power value that height should be raised to in the formula and the value that would make it achieve height independency and body fatness dependency. We randomly assigned UK Biobank participants recruited in the United Kingdom between 2006 and 2010 (n = 489,873; mean age = 56.5 years; 94.2% White) to training and testing sets (80%:20%). Using height raised to the power of -50.00 to 50.00, we identified the optimal power value that either minimized correlation with height or maximized correlation with body fat percentage, using age-adjusted correlations. The optimal power values for height were 1.77 for males and 1.39 for females. The new formulas resulted in 4.5% of females and 2.4% of males being reclassified into a different BMI category. The formulas did not show significant improvement (in terms of area under the receiver operating characteristic curve, sensitivity, and specificity) in identifying individuals with excessive body fat percentage or in predicting risk of all-cause mortality. Therefore, the conventional BMI formula is still valuable in research and disease screening for both sexes.


Assuntos
Bancos de Espécimes Biológicos , Biobanco do Reino Unido , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Índice de Massa Corporal , Peso Corporal , Tecido Adiposo , Adiposidade , Estatura
6.
Small ; 20(16): e2306964, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38072815

RESUMO

In this study, single-crystalline BiSBr is synthesized using a solution-based approach and conducted a systematic characterization of its photoelectric properties and photovoltaic performances. UV photoelectron spectroscopy and density functional theory (DFT) calculations reveal that BiSBr is an indirect p-type semiconductor, characterized by distinct positions and compositions of the valence band maximum and conduction band minimum. The BiSBr single crystal microrod features a significant electrical conductivity of 14 800 S m-1 along the c-axis, denoting minimal carrier resistance in this direction. For photovoltaic performance assessment, the authors successfully fabricated two homogeneous BiSBr films on TiO2 porous substrates: A microsheet array film via physical vapor deposition (PVD) and solvothermal treatment, and a BiSBr microsheet film via PVD and thermal treatment. The solar cell, comprising a BiSBr microsheet array film with an architecture of fluorine-doped tin oxide FTO/TiO2/BiSBr/(I3 -/I-)/Pt, demonstrated a power conversation efficiency of 1.40%, ≈11 times that of BiSBr microsheet film counterpart. These preliminary results underscore the potential of BiSBr microsheet arrays, producible through low-cost solution processes, as adept light absorbers, enhancing photovoltaic efficiency through effective light scattering and promoting efficient electron-hole separation and transport.

8.
Plant Physiol ; 192(2): 967-981, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-36822628

RESUMO

Grain yield and grain quality are major determinants in modern breeding controlled by many quantitative traits loci (QTLs) in rice (Oryza sativa). However, the mechanisms underlying grain shape and quality are poorly understood. Here, we characterize a QTL for grain size and grain quality via map-based cloning from wild rice (W1943), GS10 (Grain Size on Chromosome 10), which encodes a protein with 6 tandem armadillo repeats. The null mutant gs10 shows slender and narrow grains with altered cell size, which has a pleiotropic effect on other agronomical traits. Functional analysis reveals that GS10 interacts with TUD1 (Taihu Dwarf1) and is epistatic to OsGSK2 (glycogen synthase kinase 2) through regulating grain shape and lamina joint inclination, indicating it is negatively involved in brassinosteroid (BR) signaling. Pyramiding gs10 and the grain size gene GW5 into cultivar GLA4 substantially improved grain shape and appearance quality. Natural variation analysis revealed that gs10 from the wild rice Oryza rufipogon W1943 is a rare allele across the rice population. Collectively, these findings advance our understanding of the underlying mechanism of grain shape and provide the beneficial allele of gs10 for future rice breeding and genetic improvement.


Assuntos
Brassinosteroides , Oryza , Brassinosteroides/metabolismo , Grão Comestível/genética , Oryza/genética , Fenótipo , Melhoramento Vegetal , Locos de Características Quantitativas/genética
9.
Cardiovasc Diabetol ; 23(1): 150, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702777

RESUMO

BACKGROUND: Vasculopathy is the most common complication of diabetes. Endothelial cells located in the innermost layer of blood vessels are constantly affected by blood flow or vascular components; thus, their mechanosensitivity plays an important role in mediating vascular regulation. Endothelial damage, one of the main causes of hyperglycemic vascular complications, has been extensively studied. However, the role of mechanosensitive signaling in hyperglycemic endothelial damage remains unclear. METHODS: Vascular endothelial-specific Piezo1 knockout mice were generated to investigate the effects of Piezo1 on Streptozotocin-induced hyperglycemia and vascular endothelial injury. In vitro activation or knockdown of Piezo1 was performed to evaluate the effects on the proliferation, migration, and tubular function of human umbilical vein endothelial cells in high glucose. Reactive oxygen species production, mitochondrial membrane potential alternations, and oxidative stress-related products were used to assess the extent of oxidative stress damage caused by Piezo1 activation. RESULTS: Our study found that in VECreERT2;Piezo1flox/flox mice with Piezo1 conditional knockout in vascular endothelial cells, Piezo1 deficiency alleviated streptozotocin-induced hyperglycemia with reduced apoptosis and abscission of thoracic aortic endothelial cells, and decreased the inflammatory response of aortic tissue caused by high glucose. Moreover, the knockout of Piezo1 showed a thinner thoracic aortic wall, reduced tunica media damage, and increased endothelial nitric oxide synthase expression in transgenic mice, indicating the relief of endothelial damage caused by hyperglycemia. We also showed that Piezo1 activation aggravated oxidative stress injury and resulted in severe dysfunction through the Ca2+-induced CaMKII-Nrf2 axis in human umbilical vein endothelial cells. In Piezo1 conditional knockout mice, Piezo1 deficiency partially restored superoxide dismutase activity and reduced malondialdehyde content in the thoracic aorta. Mechanistically, Piezo1 deficiency decreased CaMKII phosphorylation and restored the expression of Nrf2 and its downstream molecules HO-1 and NQO1. CONCLUSION: In summary, our study revealed that Piezo1 is involved in high glucose-induced oxidative stress injury and aggravated endothelial dysfunction, which have great significance for alleviating endothelial damage caused by hyperglycemia.


Assuntos
Glicemia , Diabetes Mellitus Experimental , Células Endoteliais da Veia Umbilical Humana , Canais Iônicos , Camundongos Knockout , Óxido Nítrico Sintase Tipo III , Estresse Oxidativo , Animais , Humanos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Diabetes Mellitus Experimental/metabolismo , Canais Iônicos/metabolismo , Canais Iônicos/genética , Glicemia/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Mecanotransdução Celular , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/deficiência , Células Cultivadas , Proliferação de Células , Apoptose , Masculino , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/fisiopatologia , Angiopatias Diabéticas/patologia , Angiopatias Diabéticas/genética , Angiopatias Diabéticas/etiologia , Movimento Celular , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Aorta Torácica/fisiopatologia , Camundongos , Estreptozocina , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Endotélio Vascular/patologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética
10.
Ann Hematol ; 103(3): 999-1005, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38285081

RESUMO

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that is highly aggressive with a poor prognosis. There is no standard treatment for BPDCN. Although conventional chemotherapies are usually sensitive in the initial therapy, relapse and drug resistance are inevitable within a short duration. Targeted therapies have enlightened new prospects for the treatment of BPDCN, especially for those in a frail state and intolerable to standard chemotherapies or hematopoietic stem cell transplantation. Here, we report an 82-year-old man diagnosed with cutaneous-limited BPDCN. Considering the old age and limited involvement of the tumor, we reduced the dosage of venetoclax. His skin lesions subsided significantly after 1 cycle of azacytidine (100 mg d1-7) combined with reduced doses of venetoclax (200 mg d1-14). The reduction in the dose of venetoclax avoided severe myelosuppression while achieving satisfactory outcomes. The patient received 2 cycles of therapy with no skin lesions re-occurred for 7 months before relapsing.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Neoplasias Hematológicas , Transtornos Mieloproliferativos , Neoplasias Cutâneas , Sulfonamidas , Masculino , Humanos , Idoso de 80 Anos ou mais , Azacitidina/uso terapêutico , Células Dendríticas/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Hematológicas/terapia , Transtornos Mieloproliferativos/patologia
11.
Cell Commun Signal ; 22(1): 113, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347570

RESUMO

Chronic kidney disease (CKD) has historically been a significant global health concern, profoundly impacting both life and well-being. In the process of CKD, with the gradual loss of renal function, the incidence of various life-threatening complications, such as cardiovascular diseases, cerebrovascular accident, infection and stroke, is also increasing rapidly. Unfortunately, existing treatments exhibit limited ability to halt the progression of kidney injury in CKD, emphasizing the urgent need to delve into the precise molecular mechanisms governing the occurrence and development of CKD while identifying novel therapeutic targets. Renal fibrosis, a typical pathological feature of CKD, plays a pivotal role in disrupting normal renal structures and the loss of renal function. Ferroptosis is a recently discovered iron-dependent form of cell death characterized by lipid peroxide accumulation. Ferroptosis has emerged as a potential key player in various diseases and the initiation of organ fibrosis. Substantial evidence suggests that ferroptosis may significantly contribute to the intricate interplay between CKD and its progression. This review comprehensively outlines the intricate relationship between CKD and ferroptosis in terms of iron metabolism and lipid peroxidation, and discusses the current landscape of pharmacological research on ferroptosis, shedding light on promising avenues for intervention. It further illustrates recent breakthroughs in ferroptosis-related regulatory mechanisms implicated in the progression of CKD, thereby providing new insights for CKD treatment. Video Abstract.


Assuntos
Doenças Cardiovasculares , Ferroptose , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/complicações , Morte Celular , Ferro
12.
Pharmacol Res ; 205: 107263, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38876442

RESUMO

Pressure overload-induced pathological cardiac hypertrophy eventually leads to heart failure (HF). Unfortunately, lack of effective targeted therapies for HF remains a challenge in clinical management. Mixed-lineage leukemia 4 (MLL4) is a member of the SET family of histone methyltransferase enzymes, which possesses histone H3 lysine 4 (H3K4)-specific methyltransferase activity. However, whether and how MLL4 regulates cardiac function is not reported in adult HF. Here we report that MLL4 is required for endoplasmic reticulum (ER) stress homeostasis of cardiomyocytes and protective against pressure overload-induced cardiac hypertrophy and HF. We observed that MLL4 is increased in the heart tissue of HF mouse model and HF patients. The cardiomyocyte-specific deletion of Mll4 (Mll4-cKO) in mice leads to aggravated ER stress and cardiac dysfunction following pressure overloading. MLL4 knockdown neonatal rat cardiomyocytes (NRCMs) also display accelerated decompensated ER stress and hypertrophy induced by phenylephrine (PE). The combined analysis of Cleavage Under Targets and Tagmentation sequencing (CUT&Tag-seq) and RNA sequencing (RNA-seq) data reveals that, silencing of Mll4 alters the chromatin landscape for H3K4me1 modification and gene expression patterns in NRCMs. Interestingly, the deficiency of MLL4 results in a marked reduction of H3K4me1 and H3K27ac occupations on Thrombospondin-4 (Thbs4) gene loci, as well as Thbs4 gene expression. Mechanistically, MLL4 acts as a transcriptional activator of Thbs4 through mono-methylation of H3K4 and further regulates THBS4-dependent ER stress response, ultimately plays a role in HF. Our study indicates that pharmacologically targeting MLL4 and ER stress might be a valid therapeutic approach to protect against cardiac hypertrophy and HF.


Assuntos
Estresse do Retículo Endoplasmático , Insuficiência Cardíaca , Histona-Lisina N-Metiltransferase , Camundongos Endogâmicos C57BL , Miócitos Cardíacos , Animais , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/etiologia , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Masculino , Humanos , Camundongos Knockout , Ratos , Camundongos , Células Cultivadas , Cardiomegalia/metabolismo , Cardiomegalia/genética , Ratos Sprague-Dawley , Trombospondinas
13.
Artigo em Inglês | MEDLINE | ID: mdl-38913036

RESUMO

A novel chemoheterotrophic iron-reducing micro-organism, designated as strain LSZ-M11000T, was isolated from sediment of the Marianas Trench. Phylogenetic analysis based on the 16S rRNA gene revealed that strain LSZ-M11000T belonged to genus Tepidibacillus, with 97 % identity to that of Tepidibacillus fermentans STGHT, a mesophilic bacterium isolated from the Severo-Stavropolskoye underground gas storage facility in Russia. The polar lipid profile of strain LSZ-M11000T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, as well as other unidentified phospholipids and lipids. The major fatty acids were C16 : 0 (28.4 %), C18 : 0 (15.8 %), iso-C15 : 0 (12.9 %), and anteiso-C15 : 0 (12.0 %). Strain LSZ-M11000T had no menaquinone. Genome sequencing revealed that the genome size of strain LSZ-M11000T was 2.97 Mb and the DNA G+C content was 37.9 mol%. The average nucleotide identity values between strain LSZ-M11000T and its close phylogenetic relatives, Tepidibacillus fermentans STGHT and Tepidibacillus decaturensis Z9T, were 76.4 and 72.6 %, respectively. The corresponding DNA-DNA hybridization estimates were 20.9 and 23.4 %, respectively. Cells of strain LSZ-M11000T were rod-shaped (1.0-1.5×0.3-0.5 µm). Using pyruvate as an electron donor, it was capable of reducing KMnO4, MnO2, As(V), NaNO3, NaNO2, Na2SO4, Na2S2O3, and K2Cr2O7. Based on phenotypic, genotypic, and phylogenetic evidence, strain LSZ-M11000T is proposed to be a novel strain of the genus Tepidibacillus, for which the name Tepdibacillus marianensis is proposed. The type strain is LSZ-M11000T (=CCAM 1008T=JCM 39431T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Sedimentos Geológicos , Ferro , Fosfolipídeos , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , RNA Ribossômico 16S/genética , Sedimentos Geológicos/microbiologia , DNA Bacteriano/genética , Federação Russa , Ferro/metabolismo , Processos Heterotróficos , Hibridização de Ácido Nucleico , Bacillaceae/classificação , Bacillaceae/genética , Bacillaceae/isolamento & purificação , Sequenciamento Completo do Genoma , Oxirredução
14.
Int J Legal Med ; 138(3): 767-779, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38197923

RESUMO

Monozygotic (MZ) twins are theoretically genetically identical. Although they are revealed to accumulate mutations after the zygote splits, discriminating between twin genomes remains a formidable challenge in the field of forensic genetics. Single-nucleotide variants (SNVs) are responsible for a substantial portion of genetic variation, thus potentially serving as promising biomarkers for the identification of MZ twins. In this study, we sequenced the whole genome of a pair of female MZ twins when they were 27 and 33 years old to approximately 30 × coverage using peripheral blood on an Illumina NovaSeq 6000 Sequencing System. Potentially discordant SNVs supported by whole-genome sequencing were validated extensively by amplicon-based targeted deep sequencing and Sanger sequencing. In total, we found nine bona fide post-twinning SNVs, all of which were identified in the younger genomes and found in the older genomes. None of the SNVs occurred within coding exons, three of which were observed in introns, supported by whole-exome sequencing results. A double-blind test was employed, and the reliability of MZ twin discrimination by discordant SNVs was endorsed. All SNVs were successfully detected when input DNA amounts decreased to 0.25 ng, and reliable detection was limited to seven SNVs below 0.075 ng input. This comprehensive analysis confirms that SNVs could serve as cost-effective biomarkers for MZ twin discrimination.


Assuntos
Nucleotídeos , Gêmeos Monozigóticos , Adulto , Feminino , Humanos , Biomarcadores , Mutação , Reprodutibilidade dos Testes , Gêmeos Monozigóticos/genética
15.
Inorg Chem ; 63(1): 1-26, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38109856

RESUMO

As a typical cation-exchangeable layered compound, layered titanate has a unique open layered structure. Its excellent physical and chemical properties allow its wide use in the energy, environmental protection, electronics, biology, and other fields. This paper reviews the recent progress in the research on the structure, synthesis, properties, and application of layered titanates. Various reactivities, as well as the advantages and disadvantages, of different synthetic methods are discussed. The reaction mechanism and influencing factors of the ion exchange reaction, intercalation reaction, and exfoliation reaction are analyzed. The latest research progress on layered titanates and their modified products in the fields of photocatalysis, adsorption, electrochemistry, and other applications is summarized. Finally, the future development of layered titanate and its exfoliated product two-dimensional nanosheets is proposed.

16.
J Chem Inf Model ; 64(10): 3977-3991, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38727192

RESUMO

The worldwide spread of the metallo-ß-lactamases (MBL), especially New Delhi metallo-ß-lactamase-1 (NDM-1), is threatening the efficacy of ß-lactams, which are the most potent and prescribed class of antibiotics in the clinic. Currently, FDA-approved MBL inhibitors are lacking in the clinic even though many strategies have been used in inhibitor development, including quantitative high-throughput screening (qHTS), fragment-based drug discovery (FBDD), and molecular docking. Herein, a machine learning-based prediction tool is described, which was generated using results from HTS of a large chemical library and previously published inhibition data. The prediction tool was then used for virtual screening of the NIH Genesis library, which was subsequently screened using qHTS. A novel MBL inhibitor was identified and shown to lower minimum inhibitory concentrations (MICs) of Meropenem for a panel of E. coli and K. pneumoniae clinical isolates expressing NDM-1. The mechanism of inhibition of this novel scaffold was probed utilizing equilibrium dialyses with metal analyses, native state electrospray ionization mass spectrometry, UV-vis spectrophotometry, and molecular docking. The uncovered inhibitor, compound 72922413, was shown to be 9-hydroxy-3-[(5-hydroxy-1-oxa-9-azaspiro[5.5]undec-9-yl)carbonyl]-4H-pyrido[1,2-a]pyrimidin-4-one.


Assuntos
Aprendizado de Máquina , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Inibidores de beta-Lactamases , beta-Lactamases , beta-Lactamases/metabolismo , beta-Lactamases/química , Inibidores de beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/química , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Ensaios de Triagem em Larga Escala
17.
Chem Rev ; 122(3): 3820-3878, 2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-34939420

RESUMO

With the development of advanced electronic devices and electric power systems, polymer-based dielectric film capacitors with high energy storage capability have become particularly important. Compared with polymer nanocomposites with widespread attention, all-organic polymers are fundamental and have been proven to be more effective choices in the process of scalable, continuous, and large-scale industrial production, leading to many dielectric and energy storage applications. In the past decade, efforts have intensified in this field with great progress in newly discovered dielectric polymers, fundamental production technologies, and extension toward emerging computational strategies. This review summarizes the recent progress in the field of energy storage based on conventional as well as heat-resistant all-organic polymer materials with the focus on strategies to enhance the dielectric properties and energy storage performances. The key parameters of all-organic polymers, such as dielectric constant, dielectric loss, breakdown strength, energy density, and charge-discharge efficiency, have been thoroughly studied. In addition, the applications of computer-aided calculation including density functional theory, machine learning, and materials genome in rational design and performance prediction of polymer dielectrics are reviewed in detail. Based on a comprehensive understanding of recent developments, guidelines and prospects for the future development of all-organic polymer materials with dielectric and energy storage applications are proposed.

18.
Environ Sci Technol ; 58(6): 2944-2955, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38306690

RESUMO

The estuary is an energetic area connecting the inland, river, and ocean. The migration of microplastics (MPs) in this highly complex area is tied to the entire ecosystem. In this study, the effects of cohesive SPM (clay) and noncohesive SPM (sand) on the vertical migration of positively buoyant MPs, polyethylene (PE), and negatively buoyant MPs, polytetrafluoroethylene (PTFE), in the estuarine environment under hydrodynamic disturbances were investigated. The settling of positively buoyant MPs was more reliant on the cohesive SPM compared to the settling of negatively buoyant MPs. Moreover, MPs interacting with the SPM mixture at a clay-to-sand ratio of 1:9 settled more efficiently than those interacting with clay alone. A significant positive correlation was observed between MP settling percentage and the salinity level. MP settling percentage was significantly negatively correlated with fluid shear stress for both types of MPs, meanwhile, negatively buoyant MPs were able to resist greater hydraulic disturbances. In the low-energy mixing state, for both types of MPs, the settling percentage reached about 50% in only 10 min. The resuspension process of MPs under hydrodynamic disturbances was also uncovered. Additionally, the migration and potential sites of MPs were described in the context of prevalent environmental phenomena in estuaries.


Assuntos
Material Particulado , Poluentes Químicos da Água , Material Particulado/análise , Microplásticos , Plásticos , Salinidade , Areia , Hidrodinâmica , Argila , Ecossistema , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Estuários
19.
Environ Res ; 249: 118466, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38354882

RESUMO

Global outbreaks and the spread of viral diseases in the recent years have led to a rapid increase in the usage of antiviral drugs (ATVs), the residues and metabolites of which are discharged into the natural environment, posing a serious threat to human health. There is an urgent need to develop sensitive and rapid detection tools for multiple ATVs. In this study, we developed a highly sensitive electrochemical sensor comprising a glassy carbon electrode (GCE) modified with graphitized hydroxylated multi-walled carbon nanotubes (G-MWCNT-OH) and 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6, IL) for the detection of six ATVs including famciclovir (FCV), remdesivir (REM), favipiravir (FAV), hydroxychloroquine sulfate (HCQ), cepharanthine (CEP) and molnupiravir (MOL). The morphology and structure of the G-MWCNT-OH/IL nanocomposites were characterized comprehensively, and the electroactive surface area and electron conductivity of G-MWCNT-OH/IL/GCE were determined using cyclic voltammetry and electrochemical impedance spectroscopy. The thermodynamic stability and non-covalent interactions between the G-MWCNT-OH and IL were evaluated through quantum chemical simulation calculations, and the mechanism of ATV detection using the G-MWCNT-OH/IL/GCE was thoroughly examined. The detection conditions were optimized to improve the sensitivity and stability of electrochemical sensors. Under the optimal experimental conditions, the G-MWCNT-OH/IL/GCE exhibited excellent electrocatalytic performance and detected the ATVs over a wide concentration range (0.01-120 µM). The limit of detections (LODs) were 42.3 nM, 55.4 nM, 21.9 nM, 15.6 nM, 10.6 nM, and 3.2 nM for FCV, REM, FAV, HCQ, CEP, and MOL, respectively. G-MWCNT-OH/IL/GCE was also highly stable and selective to the ATVs in the presence of multiple interfering analytes. This sensor exhibited great potential for enabling the quantitative detection of multiple ATVs in actual water environment.


Assuntos
Antivirais , Técnicas Eletroquímicas , Líquidos Iônicos , Nanotubos de Carbono , Antivirais/análise , Antivirais/química , Nanotubos de Carbono/química , Líquidos Iônicos/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Limite de Detecção , Eletrodos , Grafite/química
20.
BMC Med Imaging ; 24(1): 66, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500069

RESUMO

OBJECTIVE: To investigate the altered trends of regional homogeneity (ReHo) based on time and frequency, and clarify the time-frequency characteristics of ReHo in 48 classical trigeminal neuralgia (CTN) patients after a single pain stimulate. METHODS: All patients underwent three times resting-state functional MRI (before stimulation (baseline), after stimulation within 5 s (triggering-5 s), and in the 30th min of stimulation (triggering-30 min)). The spontaneous brain activity was investigated by static ReHo (sReHo) in five different frequency bands and dynamic ReHo (dReHo) methods. RESULTS: In the five frequency bands, the number of brain regions which the sReHo value changed in classical frequency band were most, followed by slow 4 frequency band. The left superior occipital gyrus was only found in slow 2 frequency band and the left superior parietal gyrus was only found in slow 3 frequency band. The dReHo values were changed in midbrain, left thalamus, right putamen, and anterior cingulate cortex, which were all different from the brain regions that the sReHo value altered. There were four altered trends of the sReHo and dReHo, which dominated by decreased at triggering-5 s and increased at triggering-30 min. CONCLUSIONS: The duration of brain function changed was more than 30 min after a single pain stimulate, although the pain of CTN was transient. The localized functional homogeneity has time-frequency characteristic in CTN patients after a single pain stimulate, and the changed brain regions of the sReHo in five frequency bands and dReHo complemented to each other. Which provided a certain theoretical basis for exploring the pathophysiology of CTN.


Assuntos
Mapeamento Encefálico , Neuralgia do Trigêmeo , Humanos , Neuralgia do Trigêmeo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Dor
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