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1.
BMC Genomics ; 25(1): 40, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191299

RESUMO

BACKGROUND: Viral diseases are posing threat to annual production and quality of tobacco in China. Recently, tomato spotted wilt orthotospovirus (TSWV) has been reported to infect three major crops including tobacco. Current study was aimed to investigate the population dynamics and molecular diversity of the TSWV. In the current study, to assess and identify the prevalence and evolutionary history of TSWV in tobacco crops in China, full-length genome sequences of TSWV isolates from tobacco, were identified and analyzed. METHODS: After trimming and validation, sequences of new isolates were submitted to GenBank. We identified the full-length genomes of ten TSWV isolates, infecting tobacco plants from various regions of China. Besides these, six isolates were partially sequenced. Phylogenetic analysis was performed to assess the relativeness of newly identified sequences and corresponding sequences from GenBank. Recombination and population dynamics analysis was performed using RDP4, RAT, and statistical estimation. Reassortment analysis was performed using MegaX software. RESULTS: Phylogenetic analysis of 41 newly identified sequences, depicted that the majority of the Chinese isolates have separate placement in the tree. RDP4 software predicted that RNA M of newly reported isolate YNKM-2 had a recombinant region spanning from 3111 to 3811 bp. The indication of parental sequences (YNKMXD and YNHHKY) from newly identified isolates, revealed the conservation of local TSWV population. Genetic diversity and population dynamics analysis also support the same trend. RNA M was highlighted to be more capable of mutating or evolving as revealed by data obtained from RDP4, RAT, population dynamics, and phylogenetic analyses. Reassortment analysis revealed that it might have happened in L segment of TSWV isolate YNKMXD (reported herein). CONCLUSION: Taken together, this is the first detailed study revealing the pattern of TWSV genetic diversity, and population dynamics helping to better understand the ability of this pathogen to drastically reduce the tobacco production in China. Also, this is a valuable addition to the existing worldwide profile of TSWV, especially in China, where a few studies related to TSWV have been reported including only one complete genome of this virus isolated from tobacco plants.


Assuntos
Vírus de RNA , Solanum lycopersicum , Filogenia , Evolução Biológica , China , Produtos Agrícolas , Nicotiana , RNA
2.
Oncologist ; 29(9): e1189-e1200, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-38982653

RESUMO

BACKGROUND AND OBJECTIVES: Envafolimab is the first and only globally approved subcutaneously injectable PD-L1 antibody for the treatment of instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) advanced solid tumors in adults, including those with advanced colorectal cancer that has progressed after treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. The aim of this investigation was to examine the pharmacokinetic and exposure-response (E-R) profile of envafolimab in patients with solid tumors to support the approval of fixed and alternative dose regimens. METHODS: In this study, a population pharmacokinetic (PopPK) modeling approach will be employed to quantitatively evaluate intrinsic and extrinsic covariates. Additionally, PopPK-estimated exposure parameters were used to evaluate E-R relationship for safety and efficacy to provide a theoretical basis for recommending optimal treatment regimens. Simulations were performed on the dosing regimens of body weight-based regimen of 2.50 mg/kg QW, fixed dose 150 mg QW, and 300 mg Q2W for the selection of alternative dosing regimens. Data from 4 clinical studies (NCT02827968, NCT03101488, NCT03248843, and NCT03667170) were utilized. RESULTS: The PopPK dataset comprised 182 patients with 1810 evaluable envafolimab concentration records. Finally, a one-compartment model incorporating first-order absorption, first-order linear elimination, and time-dependent elimination according to an Emax function was found to accurately describe the concentration-time data of envafolimab in patients with advanced solid tumors. Creatinine clearance and country were identified as statistically significant factors affecting clearance, but had limited clinical significance. A relative flat exposure-response relationship was observed between early measures of safety and efficacy to verify that no dose adjustment is required. Simulation results indicated that 2.50 mg/kg QW, 150 mg QW, and 300 mg Q2W regimen yield similar steady-state exposure. CONCLUSIONS: No statistically significant difference was observed between weight-based and fixed dose regimens. Model-based simulation supports the adoption of a 150 mg weekly or 300 mg biweekly dosing regimen of envafolimab in the solid tumor population, as these schedules effectively balance survival benefits and safety risks.


Assuntos
Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Injeções Subcutâneas , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Antígeno B7-H1/antagonistas & inibidores , Idoso , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacocinética
3.
J Intern Med ; 296(3): 291-297, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39073192

RESUMO

BACKGROUND: Currently, pathophysiological mechanisms of post-acute sequelae of coronavirus disease-19-cardiovascular syndrome (PASC-CVS) remain unknown. METHODS AND RESULTS: Patients with PASC-CVS exhibited significantly higher circulating levels of severe acute respiratory syndrome-coronavirus-2 spike protein S1 than the non-PASC-CVS patients and healthy controls. Moreover, individuals with high plasma spike protein S1 concentrations exhibited elevated heart rates and normalized low frequency, suggesting cardiac ß-adrenergic receptor (ß-AR) hyperactivity. Microscale thermophoresis (MST) assay revealed that the spike protein bound to ß1- and ß2-AR, but not to D1-dopamine receptor. These interactions were blocked by ß1- and ß2-AR blockers. Molecular docking and MST assay of ß-AR mutants revealed that the spike protein interacted with the extracellular loop 2 of both ß-ARs. In cardiomyocytes, spike protein dose-dependently increased the cyclic adenosine monophosphate production with or without epinephrine, indicating its allosteric effects on ß-ARs. CONCLUSION: Severe acute respiratory syndrome-coronavirus-2 spike proteins act as an allosteric ß-AR agonist, leading to cardiac ß-AR hyperactivity, thus contributing to PASC-CVS.


Assuntos
COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Glicoproteína da Espícula de Coronavírus/metabolismo , COVID-19/complicações , COVID-19/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Síndrome de COVID-19 Pós-Aguda , Idoso , Simulação de Acoplamento Molecular , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Agonistas Adrenérgicos beta/farmacologia , Agonistas Adrenérgicos beta/uso terapêutico
4.
Small ; 20(31): e2311930, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38433391

RESUMO

Human health and the environment face significant challenges of air pollution, which is predominantly caused by PM2.5 or PM10 particles. Existing control methods often require elevated energy consumption or bulky high-voltage electrical equipment. To overcome these limitations, a self-powered, convenient, and compact direct current high-voltage triboelectric nanogenerator based on triboelectrification and electrostatic breakdown effects is proposed. By optimizing the structure-design of the direct current triboelectric nanogenerator and corresponding output voltage, it can easily achieve an output voltage of over 3 kV with a high charge density of 320 µC m-2. A power management circuit is designed to overcome the influence of third domain self-breakdown, optimize 92.5% amplitude of voltage shake, and raise 5% charge utilization ratio. With a device size as tiny as 2.25 cm3, it can continuously drive carbon nanowires to generate negative ions that settle dust within 300 s. This compact, simple, efficient, and safe high-voltage direct current triboelectric nanogenerator represents a promising sustainable solution. It offers efficient dust mitigation, fostering cleaner environments, and enhancing overall health.

5.
Opt Lett ; 49(9): 2393-2396, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691727

RESUMO

Topological photonic crystals (PCs) provide an effective method for controlling how light propagates and concentrates through their topological states. However, it remains unclear whether topological states can be obtained by combining two different two-dimensional (2D) PCs with topological non-trivial states. In this Letter, two types of 2D Penrose-square (P-S) PCs are proposed. These PCs can generate topological edge states (TESs) and topological corner states (TCSs) within the low-frequency part of the bandgap. Moreover, by combining these two non-trivial PCs, a total of two groups of TESs and four groups of TCSs can be generated in both the high-frequency and low-frequency parts of the common bandgap. To the best of our knowledge, the two proposed P-S PCs offer a new platform for investigating topological photonics and related devices, providing novel approaches and perspectives for generating topological states in 2D PCs.

6.
Arch Biochem Biophys ; 754: 109942, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38387828

RESUMO

Several simple secondary structures could form complex and diverse functional proteins, meaning that secondary structures may contain a lot of hidden information and are arranged according to certain principles, to carry enough information of functional specificity and diversity. However, these inner information and principles have not been understood systematically. In our study, we designed a structure-function alphabet of helix based on reduced amino acid clusters to describe the typical features of helices and delve into the information. Firstly, we selected 480 typical helices from membrane proteins, zymoproteins, transcription factors, and other proteins to define and calculate the interval range, and the helices are classified in terms of hydrophilicity, charge and length: (1) hydrophobic helix (≤43%), amphiphilic helix (43%∼71%), and hydrophilic helix (≥71%). (2) positive helix, negative helix, electrically neutral helix and uncharged helix. (3) short helix (≤8 aa), medium-length helix (9-28 aa), and long helix (≥29 aa). Then, we designed an alphabet containing 36 triplet codes according to the above classification, so that the main features of each helix can be represented by only three letters. This alphabet not only preliminarily defined the helix characteristics, but also greatly reduced the informational dimension of protein structure. Finally, we present an application example to demonstrate the value of the structure-function alphabet in protein functional determination and differentiation.


Assuntos
Proteínas de Membrana , Fatores de Transcrição , Proteínas de Membrana/química , Estrutura Secundária de Proteína , Interações Hidrofóbicas e Hidrofílicas , Aminoácidos/química
7.
Chem Res Toxicol ; 37(1): 109-116, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-38173279

RESUMO

Ferroptosis is an iron-related cell death caused by irregular lipid peroxidation that has been implicated with a variety of disease. Erastin is a canonical ferroptosis inducer that is known to function by inhibiting system Xc- and cystine transport; however, the global interactome of erastin in cells remains unexplored. In this work, we employed a quantitative chemoproteomic approach to profile direct interacting proteins of erastin in living cells using a multifunctional photo-cross-linking probe. A number of novel erastin-interacting proteins were identified, including a serine hydrolase, ABHD6, whose overexpression showed a potentiating impact on ferroptosis. Further biochemical experiments revealed that erastin can allosterically activate ABHD6's activity to produce more arachidonic acids and elevate the level of lipid reactive oxygen species. Collectively, our work provided a global portrait of erastin-interacting proteins and discovered ABHD6 as a new ferroptosis regulator.


Assuntos
Piperazinas , Morte Celular , Piperazinas/farmacologia , Piperazinas/metabolismo , Peroxidação de Lipídeos , Espécies Reativas de Oxigênio/metabolismo
8.
Diabetes Obes Metab ; 26(2): 592-601, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37953687

RESUMO

AIM: To employ a model-informed drug development approach in facilitating decision making and expediting the clinical progress of cofrogliptin (HSK7653), a novel ultralong-acting dipeptidyl peptidase-4 (DPP-4) inhibitor, for the treatment of type 2 diabetes (T2D) via a biweekly dosing regimen. METHODS: Firstly, a population pharmacokinetics and pharmacodynamics (PopPKPD) model was developed using PK and PD data from a single ascending dose study to simulate the PK and PD time profiles of HSK7653 after multiple doses. Secondly, model-based meta-analysis (MBMA) was performed on published clinical studies of Eastern Asian subjects for all DPP-4 inhibitors. We hypothesized a consistent relationship between PK and DPP-4 inhibition in both healthy individuals and in those with T2D, establishing a quantitative correlation between DPP-4 inhibition and HbA1c. Finally, the predicted PK/DPP-4 inhibition/HbA1c profiles were validated by T2D patients in late clinical trials. RESULTS: The PK/DPP-4 inhibition/HbA1c profiles of T2D patients treated with HSK7653 matched the modelled data. Our PopPKPD and MBMA models predict multiple ascending dosing PK and PD characteristics from single ascending dosing data, as well as the long-term efficacy in T2D patients, based on healthy subjects. CONCLUSIONS: Successful waiver approval for the phase 2b dose-finding study was achieved through model-informed recommendations, facilitating the clinical development of HSK7653 and other DPP-4 inhibitors.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Humanos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Hemoglobinas Glicadas , Relação Dose-Resposta a Droga , Hipoglicemiantes/farmacologia , Dipeptidil Peptidase 4
9.
Microb Cell Fact ; 23(1): 120, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38664812

RESUMO

BACKGROUND: The conversion of plant biomass into biochemicals is a promising way to alleviate energy shortage, which depends on efficient microbial saccharification and cellular metabolism. Trichoderma spp. have plentiful CAZymes systems that can utilize all-components of lignocellulose. Acetylation of polysaccharides causes nanostructure densification and hydrophobicity enhancement, which is an obstacle for glycoside hydrolases to hydrolyze glycosidic bonds. The improvement of deacetylation ability can effectively release the potential for polysaccharide degradation. RESULTS: Ammonium sulfate addition facilitated the deacetylation of xylan by inducing the up-regulation of multiple carbohydrate esterases (CE3/CE4/CE15/CE16) of Trichoderma harzianum. Mainly, the pathway of ammonium-sulfate's cellular assimilates inducing up-regulation of the deacetylase gene (Thce3) was revealed. The intracellular metabolite changes were revealed through metabonomic analysis. Whole genome bisulfite sequencing identified a novel differentially methylated region (DMR) that existed in the ThgsfR2 promoter, and the DMR was closely related to lignocellulolytic response. ThGsfR2 was identified as a negative regulatory factor of Thce3, and methylation in ThgsfR2 promoter released the expression of Thce3. The up-regulation of CEs facilitated the substrate deacetylation. CONCLUSION: Ammonium sulfate increased the polysaccharide deacetylation capacity by inducing the up-regulation of multiple carbohydrate esterases of T. harzianum, which removed the spatial barrier of the glycosidic bond and improved hydrophilicity, and ultimately increased the accessibility of glycosidic bond to glycoside hydrolases.


Assuntos
Esterases , Metionina , Esterases/metabolismo , Esterases/genética , Metionina/metabolismo , Xilanos/metabolismo , Sulfato de Amônio/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Hypocreales/metabolismo , Hypocreales/enzimologia , Hypocreales/genética , Lignina/metabolismo , Acetilação
10.
Physiol Plant ; 176(4): e14475, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39140303

RESUMO

Rhizoctonia solani is a fungal pathogen that causes significant losses in agricultural production. Because of its rapid transmission and broad host range, the exploration of genes involved in defense responses to the infection of R. solani has become an important task. Here, we performed a time-course RNA-Seq experiment to explore crucial genes or pathways involved in host responses to R. solani AG3-TB infection at 6, 12, 24, 36, 48, and 72 hours post inoculation (hpi). GO and KEGG enrichment analysis revealed that most DEGs were enriched in the basal metabolism pathways, including carbohydrate metabolic processes and the biosynthesis of amino acids. Moreover, catalase (CAT) and superoxide dismutase (SOD) were up-regulated, and transcription factors (TFs) such as WRKY, AP2, and MYB were increased significantly compared to the control (0 hpi). Silencing of WRKY70 and catalase-3 exhibited elevated susceptibility to the fungal infection. To summarize, the TFs WRKY70 and WRKY75, genes involved in jasmonic acid (JA), salicylic acid (SA), and brassinosteroids (BR) signaling pathways, and defense-related enzymes may play crucial roles in the host responses to R. solani AG3-TB infection.


Assuntos
Resistência à Doença , Regulação da Expressão Gênica de Plantas , Doenças das Plantas , Rhizoctonia , Fatores de Transcrição , Rhizoctonia/fisiologia , Rhizoctonia/patogenicidade , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Resistência à Doença/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Ácido Salicílico/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transdução de Sinais/genética , Interações Hospedeiro-Patógeno/genética
11.
BMC Infect Dis ; 24(1): 642, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926657

RESUMO

OBJECTIVE: Given the high prevalence of hypertension among Chinese adults, this population is at a significantly increased risk of severe COVID-19 complications. The purpose of this study is to assess the willingness of Chinese hypertensive adults to receive the COVID-19 vaccine and to identify the diverse factors that shape their vaccination decisions. METHODS: Sampling was conducted utilizing multistage stratified random sampling, and ultimately, a total of 886 adult hypertensive patients from Luzhou City in Southwest China were included in this study. The questionnaire design was based on the Theory of Planned Behaviour and was used to investigate their willingness to be vaccinated with COVID-19. Structural equation modeling was employed for data analysis. RESULTS: The results showed that 75.6% of hypertensive individuals were willing to receive COVID-19 vaccination. The structural equation modeling revealed that Subjective Norms (path coefficient = 0.361, CR = 8.049, P < 0.001) and Attitudes (path coefficient = 0.253, CR = 4.447, P < 0.001) had positive effects on vaccination willingness, while Perceived Behavioral Control (path coefficient=-0.004, CR=-0.127, P = 0.899) had no significant impact on Behavioral Attitudes. Mediation analysis indicated that Knowledge (indirect path coefficient = 0.032, LLCI = 0.014, ULCI = 0.058), Risk Perception (indirect path coefficient = 0.077, LLCI = 0.038, ULCI = 0.124), and Subjective Norms (indirect path coefficient = 0.044, LLCI = 0.019, ULCI = 0.087) significantly influenced vaccination willingness through Attitudes as a mediating factor. CONCLUSION: The willingness of hypertensive individuals to receive the COVID-19 vaccination is not satisfactory. The Theory of Planned Behavior provides valuable insights into understanding their vaccination intentions. Efforts should be concentrated on enhancing the subjective norms, attitudes, and knowledge about vaccination of hypertensive patients.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Hipertensão , Intenção , SARS-CoV-2 , Vacinação , Humanos , Hipertensão/epidemiologia , Hipertensão/psicologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , COVID-19/psicologia , Masculino , Feminino , China/epidemiologia , Pessoa de Meia-Idade , Vacinas contra COVID-19/administração & dosagem , Vacinação/psicologia , Vacinação/estatística & dados numéricos , Adulto , Inquéritos e Questionários , Análise de Classes Latentes , Idoso , Conhecimentos, Atitudes e Prática em Saúde , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Estudos Transversais , População do Leste Asiático
12.
Nucleic Acids Res ; 50(W1): W633-W638, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35639512

RESUMO

Protein structure exhibits greater complexity and diversity than DNA structure, and usually affects the interpretation of the function, interactions and biological annotations. Reduced amino acid alphabets (Raaa) exhibit a powerful ability to decrease protein complexity and identify functional conserved regions, which motivated us to create RaacFold. The RaacFold provides 687 reduced amino acid clusters (Raac) based on 58 reduction methods and offers three analysis tools: Protein Analysis, Align Analysis, and Multi Analysis. The Protein Analysis and Align Analysis provide reduced representations of sequence-structure according to physicochemical similarities and computational biology strategies. With the simplified representations, the protein structure can be viewed more concise and clearer to capture biological insight than the unreduced structure. Thus, the design of artificial protein will be more convenient, and redundant interference is avoided. In addition, Multi Analysis allows users to explore biophysical variation and conservation in the evolution of protein structure and function. This supplies important information for the identification and exploration of the nonhomologous functions of paralogs. Simultaneously, RaacFold provides powerful 2D and 3D rendering performance with advanced parameters for sequences, structures, and related annotations. RaacFold is freely available at http://bioinfor.imu.edu.cn/raacfold.


Assuntos
Algoritmos , Imageamento Tridimensional , Proteínas , Aminoácidos/genética , Biologia Computacional , Bases de Dados de Proteínas , Proteínas/química , Alinhamento de Sequência , Conformação Proteica
13.
Pestic Biochem Physiol ; 204: 106106, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39277410

RESUMO

The black cutworm, Agrotis ipsilon (Lepidoptera: Noctuidae), is an important agricultural pest. Phoxim is an organophosphate insecticide that has been widely used to control A. ipsilon. The extensive application of phoxim has resulted in a reduction in phoxim susceptibility in A. ipsilon. However, the molecular mechanisms underlying phoxim tolerance in A. ipsilon remain unclear. In this work, we report the involvement of AiGSTz1, a zeta class glutathione S-transferase, in phoxim tolerance in A. ipsilon. Exposure to a sublethal concentration (LC50) of phoxim dramatically upregulated the transcription level of the AiGSTz1 gene in A. ipsilon larvae, and this upregulation might be caused by phoxim-induced oxidative stress. The recombinant AiGSTz1 protein expressed in Escherichia coli was able to metabolize phoxim. Furthermore, AiGSTz1 displayed antioxidant activity to protect against oxidative stress. Knockdown of AiGSTz1 by RNA interference significantly increased the mortality rate of A. ipsilon larvae in response to phoxim. In addition, the transcription factor AiCncC can bind to the cap 'n' collar isoform C: muscle aponeurosis fibromatosis (CncC:Maf) binding site in the putative promoter of the AiGSTz1 gene. Silencing of AiCncC resulted in a dramatic downregulation of AiGSTz1. These results indicated that AiGSTz1 is involved in phoxim tolerance and is potentially regulated by AiCncC. These findings provide valuable insights into the defense mechanisms used by A. ipsilon against phoxim.


Assuntos
Glutationa Transferase , Proteínas de Insetos , Inseticidas , Mariposas , Compostos Organotiofosforados , Fatores de Transcrição , Animais , Glutationa Transferase/metabolismo , Glutationa Transferase/genética , Compostos Organotiofosforados/farmacologia , Compostos Organotiofosforados/toxicidade , Inseticidas/farmacologia , Inseticidas/toxicidade , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Mariposas/efeitos dos fármacos , Mariposas/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Larva/efeitos dos fármacos , Resistência a Inseticidas/genética , Estresse Oxidativo/efeitos dos fármacos
14.
Pestic Biochem Physiol ; 201: 105893, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685255

RESUMO

Potato virus Y (PVY) is one of the most important pathogens in the genus Potyvirus that seriously harms agricultural production. Copper (Cu), as a micronutrient, is closely related to plant immune response. In this study, we found that foliar application of Cu could inhibit PVY infection to some extent, especially at 7 days post inoculation (dpi). To explore the effect of Cu on PVY infection, transcriptome sequencing analysis was performed on PVY-infected tobacco with or without Cu application. Several key pathways regulated by Cu were identified, including plant-pathogen interaction, inorganic ion transport and metabolism, and photosynthesis. Moreover, the results of virus-induced gene silencing (VIGS) assays revealed that NbMLP423, NbPIP2, NbFd and NbEXPA played positive roles in resistance to PVY infection in Nicotiana benthamiana. In addition, transgenic tobacco plants overexpressing NtEXPA11 showed increased resistance to PVY infection. These results contribute to clarify the role and regulatory mechanism of Cu against PVY infection, and provide candidate genes for disease resistance breeding.


Assuntos
Cobre , Resistência à Doença , Nicotiana , Doenças das Plantas , Potyvirus , Nicotiana/virologia , Nicotiana/genética , Potyvirus/fisiologia , Cobre/farmacologia , Doenças das Plantas/virologia , Resistência à Doença/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica , Plantas Geneticamente Modificadas/virologia , Regulação da Expressão Gênica de Plantas , Transcriptoma
15.
J Biol Chem ; 298(4): 101783, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35245502

RESUMO

Photosynthetic organisms have evolved light-harvesting antennae over time. In cyanobacteria, external phycobilisomes (PBSs) are the dominant antennae, whereas in green algae and higher plants, PBSs have been replaced by proteins of the Lhc family that are integrated in the membrane. Red algae represent an evolutionary intermediate between these two systems, as they employ both PBSs and membrane LHCR proteins as light-harvesting units. Understanding how red algae cope with light is not only interesting for biotechnological applications, but is also of evolutionary interest. For example, energy-dependent quenching (qE) is an essential photoprotective mechanism widely used by species from cyanobacteria to higher plants to avoid light damage; however, the quenching mechanism in red algae remains largely unexplored. Here, we used both pulse amplitude-modulated (PAM) and time-resolved chlorophyll fluorescence to characterize qE kinetics in the red alga Porphyridium purpureum. PAM traces confirmed that qE in P. purpureum is activated by a decrease in the thylakoid lumen pH, whereas time-resolved fluorescence results further revealed the quenching site and ultrafast quenching kinetics. We found that quenching exclusively takes place in the photosystem II (PSII) complexes and preferentially occurs at PSII's core antenna rather than at its reaction center, with an overall quenching rate of 17.6 ± 3.0 ns-1. In conclusion, we propose that qE in red algae is not a reaction center type of quenching, and that there might be a membrane-bound protein that resembles PsbS of higher plants or LHCSR of green algae that senses low luminal pH and triggers qE in red algae.


Assuntos
Complexo de Proteína do Fotossistema II , Porphyridium , Luz , Fotossíntese , Complexo de Proteína do Fotossistema II/metabolismo , Porphyridium/metabolismo
16.
J Am Chem Soc ; 145(23): 12673-12681, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37271942

RESUMO

Itaconate is an important antimicrobial and immunoregulatory metabolite involved in host-pathogen interactions. A key mechanistic action of itaconate is through the covalent modification of cysteine residues via Michael addition, resulting in "itaconation". However, it is unclear whether itaconate has other regulatory mechanisms. In this work, we discovered a novel type of post-translational modification by promiscuous antibody enrichment and data analysis with the open-search strategy and further confirmed it as the lysine "itaconylation". We showed that itaconylation and its precursor metabolite itaconyl-CoA undergo significant upregulation upon lipopolysaccharides (LPS) stimulation in RAW264.7 macrophages. Quantitative proteomics identified itaconylation sites in multiple functional proteins, including glycolytic enzymes and histones, some of which were confirmed by synthetic peptide standards. The discovery of lysine itaconylation opens up new areas for studying how itaconate participates in immunoregulation via protein post-translational modification.


Assuntos
Lisina , Succinatos , Lisina/metabolismo , Succinatos/química , Acilação , Histonas/metabolismo , Processamento de Proteína Pós-Traducional
17.
Environ Microbiol ; 25(2): 331-351, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36367399

RESUMO

In this study, the growth of fungi Trichoderma guizhouense NJAU4742 was significantly inhibited under acid stress, and the genes related to acid stress were identified based on transcriptome analysis. Four genes including tna1, adh2/4, and bna3 were significantly up-regulated. Meanwhile, intracellular hydrogen ions accumulated under acid stress, and ATP synthesis was induced to transport hydrogen ions to maintain hydrogen ion balance. The enhancement of glycolysis pathway was also detected, and a large amount of pyruvic acid from glycolysis was accumulated due to the activity limitation of PDH enzymes. Finally, acetaldehyde accumulated, resulting in the induction of adh2/4. In order to cope with stress caused by acetaldehyde, cells enhanced the synthesis of NAD+ by increasing the expression of tna1 and bna3 genes. NAD+ effectively improved the antioxidant capacity of cells, but the NAD+ supplement pathway mediated by bna3 could also cause the accumulation of kynurenine (KYN), which was an inducer of apoptosis. In addition, KYN had a specific promoting effect on acetaldehyde synthesis by improving the expression of eno2 gene, which led to the extremely high intracellular acetaldehyde in the cell under acidic stress. Our findings provided a route to better understand the response of filamentous fungi under acid stress.


Assuntos
Hypocreales , Trichoderma , Cinurenina/metabolismo , NAD/metabolismo , Solo , Prótons , Hypocreales/metabolismo , Apoptose/genética , Acetaldeído/metabolismo , Trichoderma/genética , Trichoderma/metabolismo
18.
Brief Bioinform ; 22(3)2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32524143

RESUMO

Sequence logos give a fast and concise display in visualizing consensus sequence. Protein exhibits greater complexity and diversity than DNA, which usually affects the graphical representation of the logo. Reduced amino acids perform powerful ability for simplifying complexity of sequence alignment, which motivated us to establish RaacLogo. As a new sequence logo generator by using reduced amino acid alphabets, RaacLogo can easily generate many different simplified logos tailored to users by selecting various reduced amino acid alphabets that consisted of more than 40 clustering algorithms. This current web server provides 74 types of reduced amino acid alphabet, which were manually extracted to generate 673 reduced amino acid clusters (RAACs) for dealing with protein alignment. A two-dimensional selector was proposed for easily selecting desired RAACs with underlying biology knowledge. It is anticipated that the RaacLogo web server will play more high-potential roles for protein sequence alignment, topological estimation and protein design experiments. RaacLogo is freely available at http://bioinfor.imu.edu.cn/raaclogo.


Assuntos
Algoritmos , Sequência de Aminoácidos , Bases de Dados de Proteínas , Alinhamento de Sequência , Análise de Sequência de Proteína , Software , Matrizes de Pontuação de Posição Específica
19.
Brief Bioinform ; 22(3)2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32987405

RESUMO

Histone lysine demethylases (KDMs) play a vital role in regulating chromatin dynamics and transcription. KDM proteins are given modular activities by its sequence motifs with obvious roles division, which endow the complex and diverse functions. In our review, according to functional features, we classify sequence motifs into four classes: catalytic motifs, targeting motifs, regulatory motifs and potential motifs. JmjC, as the main catalytic motif, combines to Fe2+ and α-ketoglutarate by residues H-D/E-H and S-N-N/Y-K-N/Y-T/S. Targeting motifs make catalytic motifs recognize specific methylated lysines, such as PHD that helps KDM5 to demethylate H3K4me3. Regulatory motifs consist of a functional network. For example, NLS, Ser-rich, TPR and JmjN motifs regulate the nuclear localization. And interactions through the CW-type-C4H2C2-SWIRM are necessary to the demethylase activity of KDM1B. Additionally, many conservative domains that have potential functions but no deep exploration are reviewed for the first time. These conservative domains are usually amino acid-rich regions, which have great research value. The arrangements of four types of sequence motifs generate that KDM proteins diversify toward modular activities and biological functions. Finally, we draw a blueprint of functional mechanisms to discuss the modular activity of KDMs.


Assuntos
Motivos de Aminoácidos , Histona Desmetilases/metabolismo , Catálise , Domínio Catalítico , Núcleo Celular/enzimologia , Cromatina/metabolismo , Histona Desmetilases/química , Humanos , Metilação , Ligação Proteica , Especificidade por Substrato
20.
Opt Express ; 31(2): 2394-2401, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36785254

RESUMO

We demonstrated a compact self-starting nanosecond Yb:YAG/V:YAG solid-state laser with cylindrical vector beams output modulated by the intracavity mode converter S-waveplate experimentally. We can deliver the stable Q-switched pulse with the highest repetition rate 3.61 kHz and minimum pulse width 26 ns at the wavelength of 1030.07 nm with the help of the V:YAG crystal. In addition, the switchable radially and azimuthally polarized beams can be realized with polarization extinction ratios of 92.3% and 89.6%, respectively. The compact laser configuration can provide solutions for generating stable nanosecond structured light, and may benefit the applications like micro/nano material processing.

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