RESUMO
Talin (herein referring to the talin-1 form), is a cytoskeletal adapter protein that binds integrin receptors and F-actin, and is a key factor in the formation and regulation of integrin-dependent cell-matrix adhesions. Talin forms the mechanical link between the cytoplasmic domain of integrins and the actin cytoskeleton. Through this linkage, talin is at the origin of mechanosignaling occurring at the plasma membrane-cytoskeleton interface. Despite its central position, talin is not able to fulfill its tasks alone, but requires help from kindlin and paxillin to detect and transform the mechanical tension along the integrin-talin-F-actin axis into intracellular signaling. The talin head forms a classical FERM domain, which is required to bind and regulate the conformation of the integrin receptor, as well as to induce intracellular force sensing. The FERM domain allows the strategic positioning of protein-protein and protein-lipid interfaces, including the membrane-binding and integrin affinity-regulating F1 loop, as well as the interaction with lipid-anchored Rap1 (Rap1a and Rap1b in mammals) GTPase. Here, we summarize the structural and regulatory features of talin and explain how it regulates cell adhesion and force transmission, as well as intracellular signaling at integrin-containing cell-matrix attachment sites.
Assuntos
Actinas , Talina , Animais , Talina/metabolismo , Integrinas/metabolismo , Adesão Celular/fisiologia , Proteínas do Citoesqueleto/metabolismo , Lipídeos , Mamíferos/metabolismoRESUMO
Pigs serve as a robust animal model for the study of human diseases, notably in the context of disorders of sex development (DSD). This study aims to investigate the phenotypic characteristics and molecular mechanisms underlying the reproductive and developmental abnormalities of 38,XX ovotestis-DSD (OT-DSD) and 38,XX testis-DSD (T-DSD) in pigs. Clinical and transcriptome sequencing analyses were performed on DSD and normal female pigs. Cytogenetic and SRY analyses confirmed that OT/T-DSD pigs exhibited a 38,XX karyotype and lacked the SRY gene. The DSD pigs had higher levels of follicle-stimulating hormone, luteinizing hormone, and progesterone, but lower testosterone levels when compared with normal male pigs. The reproductive organs of OT/T-DSD pigs exhibit abnormal development, displaying both male and female characteristics, with an absence of germ cells in the seminiferous tubules. Sex determination and development-related differentially expressed genes shared between DSD pigs were identified in the gonads, including WT1, DKK1, CTNNB1, WTN9B, SHOC, PTPN11, NRG1, and NXK3-1. DKK1 is proposed as a candidate gene for investigating the regulatory mechanisms underlying gonadal phenotypic differences between OT-DSD and T-DSD pigs. Consequently, our findings provide insights into the molecular pathogenesis of DSD pigs and present an animal model for studying into DSD in humans.
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Perfilação da Expressão Gênica , Transcriptoma , Animais , Suínos/genética , Feminino , Masculino , Doenças dos Suínos/genética , Doenças dos Suínos/metabolismo , Transtornos do Desenvolvimento Sexual/genética , Transtornos do Desenvolvimento Sexual/veterinária , Testículo/metabolismo , Gônadas/metabolismoRESUMO
BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disease characterized by complement dependent and proinflammatory activation of macrophages. However, effective treatment for complement activation in PAH is lacking. We aimed to explore the effect and mechanism of CP40-KK (a newly identified analog of selective complement C3 inhibitor CP40) in the PAH model. METHODS: We used western blotting, immunohistochemistry, and immunofluorescence staining of lung tissues from the monocrotaline (MCT)-induced rat PAH model to study macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1ß and IL-18) release. Surface plasmon resonance (SPR), ELISA, and CH50 assays were used to test the affinity between CP40-KK and rat/human complement C3. CP40-KK group rats only received CP40-KK (2 mg/kg) by subcutaneous injection at day 15 to day 28 continuously. RESULTS: C3a was significantly upregulated in the plasma of MCT-treated rats. SPR, ELISA, and CH50 assays revealed that CP40-KK displayed similar affinity binding to human and rat complement C3. Pharmacological inhibition of complement C3 cleavage (CP40-KK) could ameliorate MCT-induced NLRP3 inflammasome activity, pulmonary vascular remodeling, and right ventricular hypertrophy. Mechanistically, increased proliferation of pulmonary arterial smooth muscle cells is closely associated with macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1ß and IL-18) release. Besides, C3a enhanced IL-1ß activity in macrophages and promoted pulmonary arterial smooth muscle cell proliferation in vitro. CONCLUSION: Our findings suggest that CP40-KK treatment was protective in the MCT-induced rat PAH model, which might serve as a therapeutic option for PAH.
Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Ratos , Humanos , Animais , Hipertensão Arterial Pulmonar/tratamento farmacológico , Inflamassomos/metabolismo , Interleucina-18/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Complemento C3/metabolismo , Inativadores do Complemento/efeitos adversos , Inativadores do Complemento/metabolismo , Artéria Pulmonar/metabolismo , Citocinas/metabolismo , Modelos Animais de DoençasRESUMO
BACKGROUND: The relationship between whole grain intake and chronic kidney disease (CKD) remains uncertain. OBJECTIVE: This study aimed to evaluate the association between whole grain intake and risk of CKD in Chinese adults. METHODS: The present cross-sectional study used data from the China Health and Nutrition Survey conducted in 2009. Whole grain intake was measured using 3 consecutive 24-h dietary recalls and a household food inventory. A multivariable logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of CKD. In addition, a restricted cubic spline was used to investigate the doseâresponse relationship between whole grain and risk of CKD. RESULTS: A total of 6747 participants were included, 728 of whom had CKD. Compared with those in the lowest whole grain intake group, those in the higher grain intake group had an inverse association with risk of CKD (Q2: adjusted OR 0.70, 95% CI: 0.54, 0.89; Q3: adjusted OR 0.54, 95% CI: 0.42, 0.69; and Q4: adjusted OR 0.29, 95% CI: 0.21, 0.41). The association between whole grain intake and CKD seems to be stronger for individuals who were male (P for interaction = 0.008) or smokers (P for interaction = 0.013). In addition, the restricted cubic spline suggested an obvious L-shaped correlation. CONCLUSIONS: Increased whole grain intake was associated with a decreased risk of CKD in Chinese adults.
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Insuficiência Renal Crônica , Grãos Integrais , Adulto , Humanos , Masculino , Feminino , Estudos Transversais , Insuficiência Renal Crônica/epidemiologia , Dieta , Inquéritos NutricionaisRESUMO
BACKGROUND: The precise identification of the underlying causes of infectious diseases, such as severe pneumonia, is essential, and the development of next-generation sequencing (NGS) has enhanced the effectiveness of pathogen detection. However, there is limited information on the systematic assessment of the clinical use of targeted next-generation sequencing (tNGS) in cases of severe pneumonia. METHODS: A retrospective analysis was conducted on 130 patients with severe pneumonia treated in the ICU from June 2022 to June 2023. The consistency of the results of tNGS, metagenomics next-generation sequencing (mNGS), and culture with the clinical diagnosis was evaluated. Additionally, the results for pathogens detected by tNGS were compared with those of culture, mNGS, and quantitative reverse transcription PCR (RT-qPCR). To evaluate the efficacy of monitoring severe pneumonia, five patients with complicated infections were selected for tNGS microbiological surveillance. The tNGS and culture drug sensitisation results were then compared. RESULTS: The tNGS results for the analysis of the 130 patients showed a concordance rate of over 70% with clinical diagnostic results. The detection of pathogenic microorganisms using tNGS was in agreement with the results of culture, mNGS, and RT-qPCR. Furthermore, the tNGS results for pathogens in the five patients monitored for complicated infections of severe pneumonia were consistent with the culture and imaging test results during treatment. The tNGS drug resistance results were in line with the drug sensitivity results in approximately 65% of the cases. CONCLUSIONS: The application of tNGS highlights its promise and significance in assessing the effectiveness of clinical interventions and providing guidance for anti-infection therapies for severe pneumonia.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Pneumonia , Humanos , Estudos Retrospectivos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Pneumonia/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricosRESUMO
Fe was selected as an alloying element for the first time to prepare a new antibacterial titanium alloy based on micro-area potential difference (MAPD) antibacterial mechanism. The microstructure, the corrosion resistance, the mechanical properties, the antibacterial properties and the cell biocompatibility have been investigated in detail by optical microscopy, scanning electron microscopy, electrochemical testing, mechanical property test, plate count method and cell toxicity measurement. It was demonstrated that heat treatment had a significant on the compressive mechanical properties and the antibacterial properties. Ti-xFe (x = 3,5 and 9) alloys after 850 °C/3 h + 550 °C/62 h heat treatment exhibited strong antimicrobial properties with an antibacterial rate of more than 90% due to the MAPD caused by the redistribution of Fe element during the aging process. In addition, the Fe content and the heat treatment process had a significant influence on the mechanical properties of Ti-xFe alloy but had nearly no effect on the corrosion resistance. All Ti-xFe alloys showed non-toxicity to the MC3T3 cell line in comparison with cp-Ti, indicating that the microzone potential difference had no adverse effect on the corrosion resistance, cell proliferation, adhesion, and spreading. Strong antibacterial properties, good cell compatibility and good corrosion resistance demonstrated that Ti-xFe alloy might be a candidate titanium alloy for medical applications.
Assuntos
Ligas , Titânio , Titânio/farmacologia , Titânio/química , Ligas/farmacologia , Ligas/química , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Ferro/farmacologia , Corrosão , Teste de MateriaisRESUMO
A weak electric field (WEF, 2 mA cm-2) was employed to promote Fe(III)/Fe(II) cycle on goethite-impregnated activated carbon (FeOOH@AC) filled in a continuous-flow column for enhanced Cr(VI) elimination from water. Surficial analysis and Cr species distribution showed that α-FeOOH of 0.2-1 µm was successfully synthesized and evenly loaded onto AC. Electron transfer from WEF to α-FeOOH was facilitated with AC as electron shuttles, thereby boosting Fe(III) reduction in the α-FeOOH. The generated Fe(II) reduced Cr(VI) and the resultant Cr(III) subsequently precipitated with OH- and Fe(III) to form Cr(OH)3 and (CrχFe1-χ)(OH)3. Therefore, the WEF-FeOOH@AC column exhibited a much lower Cr(VI) migration rate of 0.0018 cm PV-1 in comparison with 0.0037 cm PV-1 of the FeOOH@AC column, equal to 104 % higher Cr(VI) elimination capacity and 90 % longer column service life-span. Additionally, under different Cr(VI) loadings by varying either seepage velocities or influent Cr(VI) concentrations, the WEF-FeOOH@AC column maintained 1.0-1.5 folds higher Cr(VI) elimination and 0.9-1.4 folds longer longevity than those of the FeOOH@AC column owing to the interaction between FeOOH@AC and WEF. Our research demonstrated that WEF-FeOOH@AC was a potential method to promote Cr(VI) elimination from water and offer an effective strategy to facilitate Fe(III)/Fe(II) cycle in iron oxides.
Assuntos
Compostos Férricos , Compostos de Ferro , Minerais , Poluentes Químicos da Água , Água , Carvão Vegetal , Oxirredução , Cromo/análise , Poluentes Químicos da Água/análise , Compostos FerrososRESUMO
AIMS: This study aims to develop an evidence-based nursing practice program to prevent unplanned endotracheal extubation (UEE) among adult patients in the intensive care unit (ICU). DESIGN: This study uses the Delphi method to develop an evidence-based nursing practice program. METHODS: A comprehensive review of 18 databases and evidence-based websites was conducted to gather, assess and synthesize evidence on preventing UEEs in adult patients. Using this synthesized evidence, a questionnaire was formulated for further investigation. Subsequently, input was solicited from experts through Delphi surveys to establish an evidence-based nursing practice protocol for preventing UEEs in adult ICU patients. Consistency in consultation results guided subsequent rounds of consultation. RESULTS: The developed program comprised 43 evidence items categorized into nine dimensions, including risk assessment for unplanned extubation, sedation, analgesia, delirium, balloon management, psychosocial care, early extubation, catheter immobilization and protective restraints. Two rounds of expert inquiry yielded recovery rates of 94.7% and 100% for the first and second questionnaires, respectively. Kendall W values ranged from .224 to .353 (p < .001). CONCLUSION: This study developed an evidence-based nursing practice program to prevent UEE in adult ICU patients, employing evidence-based practices and Delphi expert consultation methods. However, further validation of the program's effectiveness is warranted. REPORTING METHOD: Findings were reported according to the Standards for Reporting Qualitative Research checklist. PATIENT OR PUBLIC CONTRIBUTION: Nurses contributed to the study by participating in investigations. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: The program developed in this study offers an evidence-based framework for preventing unplanned extubation in hospitals, thereby reducing its incidence and enhancing the quality of nursing care.
RESUMO
In this study, nanoscale cupric oxide-decorated activated carbon (nCuO@AC) was synthesized by impregnation-calcination and employed to assist the decomposition of H2O2 for effective sterilization with Escherichia coli as target bacteria. Characteristic technologies demonstrated that copper oxide particles of 50-100 nm were uniformly distributed on AC surface. Owing to electron transfer from hydroxyl and aldehyde to CuO on AC, surface-bonded Cu(II) was partially reduced to Cu(I) in the nCuO matrix. The resultant Cu(I) expedited the decomposition of H2O2 and converted it into ·OH radicals which were identified by quenching experiment and electron paramagnetic resonance test. Due to oxidation attack of generated ·OH, the nCuO@AC-H2O2 system achieved a much higher inactivation rate of 6.0 log within 30 min as compared to those of 2.1 and 1.3 log in the nCuO@AC and nCuO-H2O2 systems. It also exhibited excellent pH adaptability and high inactivation efficiency under neutral conditions. After four cycles, the nCuO@AC-H2O2 system could still inactivate 5.5 log bacteria, indicating excellent stability and reusability of nCuO@AC. Spent nCuO@AC could be regenerated by eluting surficial copper oxides with hydrochloric acid, and re-coating nCuO particles through impregnation-calcination with a regeneration rate of 96.6%. Our results demonstrated that nCuO@AC was an efficient and prospective catalyst to assist the decomposition of H2O2 for effective inactivation of bacteria in water.
Assuntos
Carvão Vegetal , Cobre , Escherichia coli , Peróxido de Hidrogênio , Escherichia coli/efeitos dos fármacos , Peróxido de Hidrogênio/química , Cobre/química , Carvão Vegetal/química , Carbono/química , OxirreduçãoRESUMO
Zero-valent iron (Fe0) usually suffers from organic acid complexation and ferrochrome layer passivation in Cr(VI) removal from bioleached wastewater of Cr slag. In this work, a synergetic system combined Fe0 and mixed hetero/autotrophic bacteria was established to reduce and stabilize Cr(VI) from bioleached wastewater. Due to bacterial consumption of organic acid and hydrogen, severe iron corrosion and structured-Fe(II) mineral generation (e.g., magnetite and green rust) occurred on biotic Fe0 surface in terms of solid-phase characterization, which was crucial for Cr(VI) adsorption and reduction. Therefore, compared with the abiotic Fe0 system, this integrated system exhibited a 6.1-fold increase in Cr(VI) removal, with heterotrophic reduction contributing 3.4-fold and abiotic part promoted by hydrogen-autotrophic bacteria enhancing 2.7-fold. After reaction, the Cr valence distribution and X-ray photoelectron spectroscopy indicated that most Cr(VI) was converted into immobilized products such as FexCr1-x(OH)3, Cr2O3, and FeCr2O4 by biotic Fe0. Reoxidation experiment revealed that these products exhibited superior stability to the immobilized products generated by Fe0 or bacteria. Additionally, organic acid concentration and Fe0 dosage showed significantly positive correlation with Cr(VI) removal within the range of biological adaptation, which emphasized that heterotrophic and autotrophic bacteria acted essential roles in Cr(VI) removal. This work highlighted the enhanced effect of heterotrophic and autotrophic activities on Cr(VI) reduction and stabilization by Fe0 and offered a promising approach for bioleached wastewater treatment.
Assuntos
Bactérias , Cromo , Ferro , Águas Residuárias , Águas Residuárias/química , Ferro/química , Ferro/metabolismo , Cromo/metabolismo , Cromo/química , Bactérias/metabolismo , Processos Autotróficos , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/química , AdsorçãoRESUMO
Rural areas are the main source of ecosystem services in arid and semi-arid areas, and ecosystem services are the background conditions for rural revitalization. In this study, the spatial pattern of key ecosystem services in the countryside was assessed, and the trade-offs and synergistic relationships among ecosystem services were investigated, using the Tacheng-Emin Basin in China as the study area. Finally, the types of ecological function zoning and development strategies for the countryside are proposed. The results showed that: (1) the area of ecological land was large, and the average land use intensity was 2.48, which belonged to the medium intensity. (2) The mean values of the six ecosystem services are all in the middle and lower classes, and the spatial distribution of the five ecosystem services is similar, except for food production. (3) Except for grain production, the other five ecosystem services showed positive feedback to elevation. The other five ecosystem services are synergistic, and there are trade-offs between grain production and other ecosystem services. In the nonlinear interaction mechanism of ecosystem services, the fluctuation constraint occupies the largest proportion. (4) At smaller spatial scales, there are more types of ecosystem service clusters. Combining the results of the study, the villages in the study area can be categorized into five types. This study formulates five priority levels of rural ecological revitalization and proposes different development recommendations for the sustainable development of each type of village. This study is helpful for the fine management of land resources and the revitalization of rural ecology and provides a reference for the sustainable development of ecosystem services in arid and semi-arid areas.
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Conservação dos Recursos Naturais , Ecossistema , China , EcologiaRESUMO
Spatial conflicts of land use (SCLU) arise during land-use change, which causes an imbalance of land-use spatial patterns and negatively affects society, the economy, and ecology. Previous research has focused on identifying and measuring SCLU, with less attention on the negative effects. The incorporation of risk assessment methods to evaluate potential conflict risks has been limited. The current study presents methods for measuring SCLU and assessing potential conflict risks from the ecological environment perspective. The spatial comprehensive conflicts index and potential conflict risk index were used to identify and measure the SCLU and to assess and warn against potential conflict risks, respectively, based on a case study in the Ili River Valley in China. The impacts of terrain restriction and land-use change on the SCLU were explored. Results indicate that (1) the SCLU area in the Ili River Valley decreased by 2,608 km2 from 2010 to 2020, compared to the previous decade, the degree of conflict weakened, and the main body of the SCLU gradually shifted northwest. (2) The potential risk areas cover 20,268 km2 in 2020-2030 and are mainly distributed in the "Khorgas City-Huocheng County-Yining City-Yining County" group of towns, as well as along the Ili-Kunes rivers and in the ecological protection zone in the south of the Ili River Valley, which shows the clustering along the city and distribution along the river in the spatial pattern. (3) Topography had a significant impact on the SCLU, and the main types of land-use change in the severe-conflict zone were the reduction of grassland and the expansion of arable and built-up land. For future conflict mitigation in the Ili River Valley, cautioning against urban sprawl and safeguarding land ecological security is critical. This study systematically investigates and analyzes SCLU across three dimensions: theory, methodology, and application to produce a theoretical and practical framework to identify SCLU and assess potential conflict risks.
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Conservação dos Recursos Naturais , Rios , Cidades , China , Medição de Risco , EcossistemaRESUMO
AIMS: Ossifying fibromyxoid tumor (OFMT) is a rare enigmatic tumor of uncertain differentiation that can be classified as typical, atypical, and malignant subtypes based on cellularity, nuclear grade, and mitotic activity. The majority of OFMTs, regardless of the risk of malignancy, harbor genetic translocations. We report two malignant OFMTs, including one with evidence of dedifferentiation, with novel genefusions. METHODS AND RESULTS: Case 1 was a 63-year-old male with a dedifferentiated OFMT arising in the right wrist, while case 2 was a 41-year-old male with a malignant OFMT presenting as a posterior mediastinal mass. Case 2 showed multifocal expression with EMA and synaptophysin, while desmin and S100 were absent in both tumors. NGS sequencing studies detected PHF1::FOXR1 and PHF1::FOXR2 gene fusions in cases 1 and 2, respectively. Despite aggressive regimens, both progressed with wide spread metastases resulting in death within six years of diagnosis. CONCLUSIONS: We expand the genetic spectrum of OFMTs with two novel gene fusions, PHF1::FOXR1 and PHF1::FOXR2. These cases confirm the previously reported tendencies for OFMTs with rare variant fusions to demonstrate malignant behavior, unusual morphology, and non-specific immunophenotype.
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Fibroma Ossificante , Fibroma , Neoplasias de Tecidos Moles , Masculino , Humanos , Pessoa de Meia-Idade , Adulto , Fibroma Ossificante/patologia , Neoplasias de Tecidos Moles/patologia , Fibroma/patologia , Fusão Gênica , Proteínas de Ligação a DNA/genética , Proteínas do Grupo Polycomb/genética , Proteínas do Grupo Polycomb/metabolismo , Fatores de Transcrição Forkhead/genéticaRESUMO
Binding of the intracellular adapter proteins talin and its cofactor, kindlin, to the integrin receptors induces integrin activation and clustering. These processes are essential for cell adhesion, migration, and organ development. Although the talin head, the integrin-binding segment in talin, possesses a typical FERM-domain sequence, a truncated form has been crystallized in an unexpected, elongated form. This form, however, lacks a C-terminal fragment and possesses reduced ß3-integrin binding. Here, we present a crystal structure of a full-length talin head in complex with the ß3-integrin tail. The structure reveals a compact FERM-like conformation and a tightly associated N-P-L-Y motif of ß3-integrin. A critical C-terminal poly-lysine motif mediates FERM interdomain contacts and assures the tight association with the ß3-integrin cytoplasmic segment. Removal of the poly-lysine motif or disrupting the FERM-folded configuration of the talin head significantly impairs integrin activation and clustering. Therefore, structural characterization of the FERM-folded active talin head provides fundamental understanding of the regulatory mechanism of integrin function.
Assuntos
Integrina beta3/metabolismo , Talina/química , Talina/metabolismo , Motivos de Aminoácidos , Animais , Sítios de Ligação , Humanos , Integrina beta3/química , Leucina/metabolismo , Camundongos , Microscopia Eletrônica de Transmissão , Modelos Moleculares , Mutagênese , Polilisina/química , Domínios Proteicos , Dobramento de Proteína , Talina/genéticaRESUMO
Multimodal sensor with high sensitivity, accurate sensing resolution, and stimuli discriminability is very desirable for human physiological state monitoring. A dual-sensing aerogel is fabricated with independent pyro-piezoresistive behavior by leveraging MXene and semicrystalline polymer to assemble shrinkable nanochannel structures inside multilevel cellular walls of aerogel for discriminable temperature and pressure sensing. The shrinkable nanochannels, controlled by the melt flow-triggered volume change of semicrystalline polymer, act as thermoresponsive conductive channels to endow the pyroresistive aerogel with negative temperature coefficient of resistance of -10.0% °C-1 and high accuracy within 0.2 °C in human physiological temperature range of 30-40 °C. The flexible cellular walls, working as pressure-responsive conductive channels, enable the piezoresistive aerogel to exhibit a pressure sensitivity up to 777 kPa-1 with a detectable pressure limit of 0.05 Pa. The pyro-piezoresistive aerogel can detect the temperature-dependent characteristics of pulse pressure waveforms from artery vessels under different human body temperature states.
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Polímeros , Condutividade Elétrica , Humanos , Monitorização Fisiológica , TemperaturaRESUMO
Cotton (Gossypium hirsutum) is constantly attacked by pathogens and insects. The most efficient control strategy is to develop resistant varieties using broad-spectrum gene resources. Several resistance loci harboured by superior varieties have been identified through genome-wide association studies. However, the key genes and/or loci have not been functionally identified. In this study, we identified a locus significantly associated with Verticillium wilt (VW) resistance, and within a 145.5-kb linkage disequilibrium, two non-specific lipid transfer protein genes (named GhnsLTPsA10) were highly expressed under Verticillium pathogen stress. The expression of GhnsLTPsA10 significantly increased in roots upon Verticillium dahliae stress but significantly decreased in leaves under insect attack. Furthermore, GhnsLTPsA10 played antagonistic roles in positively regulating VW and Fusarium wilt resistance and negatively mediating aphid and bollworm resistance in transgenic Arabidopsis and silenced cotton. By combining transcriptomic, histological and physiological analyses, we determined that GhnsLTPsA10-mediated phenylpropanoid metabolism further affected the balance of the downstream metabolic flux of flavonoid and lignin biosynthesis. The divergent expression of GhnsLTPsA10 in roots and leaves coordinated resistance of cotton against fungal pathogens and insects via the redirection of metabolic flux. In addition, GhnsLTPsA10 contributed to reactive oxygen species accumulation. Therefore, in this study, we elucidated the novel function of GhnsLTP and the molecular association between disease resistance and insect resistance, balanced by GhnsLTPsA10. This broadens our knowledge of the biological function of GhnsLTPsA10 in crops and provides a useful locus for genetic improvement of cotton.
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Proteínas de Transporte/metabolismo , Metabolismo Energético/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , Gossypium/metabolismo , Doenças das Plantas/imunologia , Proteínas de Plantas/metabolismo , Animais , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Transporte/genética , Metabolismo Energético/genética , Estudo de Associação Genômica Ampla , Gossypium/genética , Herbivoria , Insetos , Larva , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Verticillium/fisiologiaRESUMO
Integrin activation and clustering by talin are early steps of cell adhesion. Membrane-bound talin head domain and kindlin bind to the ß integrin cytoplasmic tail, cooperating to activate the heterodimeric integrin, and the talin head domain induces integrin clustering in the presence of Mn2+ Here we show that kindlin-1 can replace Mn2+ to mediate ß3 integrin clustering induced by the talin head, but not that induced by the F2-F3 fragment of talin. Integrin clustering mediated by kindlin-1 and the talin head was lost upon deletion of the flexible loop within the talin head F1 subdomain. Further mutagenesis identified hydrophobic and acidic motifs in the F1 loop responsible for ß3 integrin clustering. Modeling, computational and cysteine crosslinking studies showed direct and catalytic interactions of the acidic F1 loop motif with the juxtamembrane domains of α- and ß3-integrins, in order to activate the ß3 integrin heterodimer, further detailing the mechanism by which the talin-kindlin complex activates and clusters integrins. Moreover, the F1 loop interaction with the ß3 integrin tail required the newly identified compact FERM fold of the talin head, which positions the F1 loop next to the inner membrane clasp of the talin-bound integrin heterodimer.This article has an associated First Person interview with the first author of the paper.
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Integrina beta3 , Talina , Adesão Celular , Análise por Conglomerados , Integrina beta3/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Talina/genética , Talina/metabolismoRESUMO
BACKGROUND: The article aims to study the results of EB virus nucleic acid quantification (EBV-DNA) in whole blood lymphocytes to examine whether serum can diagnose EB virus infection in children. Group A consisted of 65 children admitted to the hospital with a probable EB virus infection between February 2017 and February 2018. In the same period of health check-ups, 65 children were randomly selected as Group B. METHODS: To find out the differences between Group A and Group B, EBV-DNAs in whole blood lymphocyte and serum were detected by quantitative fluorescence assay, and EBV-CA-IgM antibody was detected by enzyme-linked immunosorbent assay. RESULTS: The results demonstrate that Group A had a greater rate of positive EBV-DNAs in whole blood lymphocytes and serum than Group B. EBV-DNA positivity was greater in whole blood lymphocytes of Group A and Group B than in serum. In whole blood lymphocytes from Group A, the positive rate of EBV-DNA and EBV-CA-IgM antibodies was statistically significant. CONCLUSION: The positive rate of EBV-DNA in whole blood lymphocytes of EBV-infected children is higher than in serum, the suitable specimens for diagnosis should be chosen based on the individual condition of children patients.
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Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Anticorpos Antivirais , Criança , DNA Viral , Infecções por Vírus Epstein-Barr/diagnóstico , Humanos , Imunoglobulina M , LinfócitosRESUMO
Influenza A virus (IAV) H1N1 infection remains great challenge to public health and causes great burden over the world. Although there are anti-viral agents available, searching for effective agents to treat H1N1 infection is still in urgent because of the emergence of resistant strain. Protocatechuic acid (PCA) is a biological agent with multiple functions. In present study, we explored the effects of PCA on H1N1 infection. Mice infected with mouse adapted influenza strain A/Font Monmouth were administrated with PCA. The body weight change, mortality, lung index, viral titer, immune cell infiltration, and cytokine production in the lung were monitored. The activation of toll-like receptor 4 (TLR4) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) pathway was investigated. PCA treatment prevented H1N1 infection-induced mice body weight loss and death. PCA reduced the lung index, viral titer, infiltration of immune cells, and cytokine level in the lung, as well as suppressed H1N1-induced TLR4/NF-κB activation. PCA protects mice against H1N1 infection and could be a potential therapeutic agent to treat influenza.
Assuntos
Hidroxibenzoatos , Vírus da Influenza A Subtipo H1N1 , Infecções por Orthomyxoviridae , Animais , Modelos Animais de Doenças , Hidroxibenzoatos/farmacologia , Hidroxibenzoatos/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/prevenção & controle , Ativação Transcricional/efeitos dos fármacosRESUMO
Prostate cancer is a common clinical disease in men. It is known that prostate cancer ranks 3rd in the incidence of malignant tumors of the male genitourinary system in China, which is able to evaluate the riskiness of life expectancy of male patients. Therefore, we investigated the expression of CD133, recombinant human kallikrein 3 (Klk3), grainy head like 2 (grhl2) in prostate cancer, and correlation with tumor characteristics in the present study. A total of 167 prostate cancer patients who underwent surgical treatment in our hospital from February 2017 to April 2021 were selected. Their cancer and adjacent tissues were resected, and CD133 was detected by double staining using immunohistochemistry, Klk3 and grhl2 were detected by RT-PCR analysis, and CD133, Klk3 were analyzed by Pearson's method in different clinical stages, Gleason grade Correlation of grhl2 with tumor characteristics. The expression of CD133, KLK3, and GRHL2 in cancer tissue was increased compared with adjacent tissue (P < 0.05). The expression of CD133, KLK3, and GRHL2 increased with the aggravation of the clinical stage and Gleason grade (P < 0.05). CD133, KLK3, and GRHL2 showed a positive correlation in prostate cancer. The Pearson method found a positive correlation between CD133, KLK3, GRHL2 and clinical stage, Gleason grade, and lymph node metastasis. In general, high CD133, Klk3, and grhl2 expression was observed in prostate cancer and increased with the disease. They presented a positive correlation in prostate cancer presence, and these three gene products correlated with tumor characteristics.