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1.
J Virol ; 98(5): e0048324, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38639486

RESUMO

Alphaherpesvirus pseudorabies virus (PRV) causes severe economic losses to the global pig industry and has garnered increasing attention due to its broad host range including humans. PRV has developed a variety of strategies to antagonize host antiviral innate immunity. However, the underlying mechanisms have not been fully elucidated. In our previous work, we demonstrated that non-muscle myosin heavy chain IIA (NMHC-IIA), a multifunctional cytoskeleton protein, attenuates innate immune responses triggered by RNA viruses. In the current study, we reported a previously unrecognized role of NMHC-IIA in counteracting PRV-induced cyclic GMP-AMP synthase (cGAS)-dependent type I interferon (IFN-I) production. Mechanistically, PRV infection led to an elevation of NMHC-IIA, strengthening the interaction between poly (ADP-ribose) polymerase 1 (PARP1) and cGAS. This interaction impeded cGAS recognition of PRV DNA and hindered downstream signaling activation. Conversely, inhibition of NMHC-IIA by Blebbistatin triggered innate immune responses and enhanced resistance to PRV proliferation both in vitro and in vivo. Taken together, our findings unveil that PRV utilizes NMHC-IIA to antagonize host antiviral immune responses via impairing DNA sensing by cGAS. This in-depth understanding of PRV immunosuppression not only provides insights for potential PRV treatment strategies but also highlights NMHC-IIA as a versatile immunosuppressive regulator usurped by both DNA and RNA viruses. Consequently, NMHC-IIA holds promise as a target for the development of broad-spectrum antiviral drugs.IMPORTANCECyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis plays a vital role in counteracting alphaherpesvirus infections. Alphaherpesviruses exploit various strategies for antagonizing cGAS-STING-mediated antiviral immune responses. However, limited examples of pseudorabies virus (PRV)-caused immunosuppression have been documented. Our findings reveal a novel role of non-muscle myosin heavy chain IIA (NMHC-IIA) in suppressing PRV-triggered innate immune responses to facilitate viral propagation both in vitro and in vivo. In detail, NMHC-IIA recruits poly (ADP-ribose) polymerase 1 (PARP1) to augment its interaction with cGAS, which impairs cGAS recognition of PRV DNA. Building on our previous demonstration of NMHC-IIA's immunosuppressive role during RNA virus infections, these findings indicate that NMHC-IIA acts as a broad-spectrum suppressor of host antiviral innate immunity in response to both DNA and RNA viruses. Therefore, NMHC-IIA will be a promising target for the development of comprehensive antiviral strategies.


Assuntos
Herpesvirus Suídeo 1 , Imunidade Inata , Miosina não Muscular Tipo IIA , Pseudorraiva , Animais , Humanos , Camundongos , Linhagem Celular , DNA Viral/imunologia , Células HEK293 , Herpesvirus Suídeo 1/imunologia , Interferon Tipo I/metabolismo , Interferon Tipo I/imunologia , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/imunologia , Miosina não Muscular Tipo IIA/metabolismo , Nucleotidiltransferases/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Pseudorraiva/imunologia , Pseudorraiva/virologia , Transdução de Sinais , Suínos
2.
J Am Chem Soc ; 146(29): 19748-19755, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38980287

RESUMO

Hybrid halide perovskites are good candidates for a range of functional materials such as optical electronic and photovoltaic devices due to their tunable band gaps, long carrier diffusion lengths, and solution processability. However, the instability in moisture/air, the toxicity of lead, and rigorous reaction setup or complex postprocessing have long been the bottlenecks for practical application. Herein, we present a simultaneous configurational entropy design at A-sites, B-sites, and X-sites in the typical (CHA)2PbBr4 two-dimensional (2D) hybrid perovskite. Our results demonstrate that the high-entropy effect favors the stabilization of the hybrid perovskite phase and facilitates a simple crystallization process without precise control of the cooling rate to prepare regular crystals. Moreover, high-entropy 2D perovskite crystals exhibit tunable energy band gaps, broadband emission, and a long carrier lifetime. Meanwhile, the high-entropy composition almost maintains the initial crystal structure in deionized water for 18 h while the original (CHA)2PbBr4 crystal mostly decomposes, suggesting obviously improved humidity stability. This work offers a facile approach to synthesize humidity-stable hybrid perovskites under mild conditions, accelerating relevant preparation of optoelectronics and light-emitting devices and facilitating the ultimate commercialization of halide perovskite.

3.
Small ; 20(35): e2401664, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38651220

RESUMO

Cellulose nanocrystal (CNC), as a renewable resource, with excellent mechanical performance, low thermal expansion coefficient, and unique optical performance, is becoming a novel candidate for the development of smart material. Herein, the recent progress of CNC-based chirality nanomaterials is uncovered, mainly covering structure regulations and function design. Undergoing a simple evaporation process, the cellulose nanorods can spontaneously assemble into chiral nematic films, accompanied by a vivid structural color. Various film structure-controlling strategies, including assembly means, physical modulation, additive engineering, surface modification, geometric structure regulation, and external field optimization, are summarized in this work. The intrinsic correlation between structure and performance is emphasized. Next, the applications of CNC-based nanomaterials is systematically reviewed. Layer-by-layer stacking structure and unique optical activity endow the nanomaterials with wide applications in the mineralization, bone regeneration, and synthesis of mesoporous materials. Besides, the vivid structural color broadens the functions in anti-counterfeiting engineering, synthesis of the shape-memory and self-healing materials. Finally, the challenges for the CNC-based nanomaterials are proposed.

4.
Arch Microbiol ; 206(10): 409, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39302440

RESUMO

The widespread spread of bacterial antimicrobial resistance (AMR) and multidrug-resistant bacteria poses a significant threat to global public health. Traditional methods for detecting bacterial AMR are simple, reproducible, and intuitive, requiring long time incubation and high labor intensity. To quickly identify and detect bacterial AMR is urgent for clinical treatment to reduce mortality rate, and many new methods and technologies were required to be developed. This review summarizes the current phenotypic and genotypic detection methods for bacterial AMR. Phenotypic detection methods mainly include antimicrobial susceptibility tests, while genotypic detection methods have higher sensitivity and specificity and can detect known or even unknown drug resistance genes. However, most of the current tests are either genotypic or phenotypic and rarely combined. Combining the advantages of phenotypic and genotypic methods, combined with the joint application of multiple rapid detection methods may be the trend for future AMR testing. Driven by rapid diagnostic technology, big data analysis, and artificial intelligence, detection methods of bacterial AMR are expected to constantly develop and innovate. Adopting rational detection methods and scientific data analysis can better address the challenges of bacterial AMR and ensure human health and social well-being.


Assuntos
Antibacterianos , Bactérias , Farmacorresistência Bacteriana , Genótipo , Testes de Sensibilidade Microbiana , Saúde Única , Fenótipo , Humanos , Antibacterianos/farmacologia , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Farmacorresistência Bacteriana/genética , Infecções Bacterianas/microbiologia , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla/genética
5.
Eur Radiol ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39210161

RESUMO

OBJECTIVES: This study aimed to utilize MR radiomics-based machine learning classifiers on a large-sample, multicenter dataset to develop an optimal model for predicting malignant sinonasal tumors and tumor-like lesions. METHODS: This study included 1711 adult patients (875 benign and 836 malignant) with sinonasal tumors or tumor-like lesions from three institutions. Patients from institution 1 (n = 1367) constituted both the training and validation cohorts, while those from institution 2 and 3 (n = 158/186) made up the test cohorts. Manual segmentation of the region of interest of the tumor was performed on T1WI, T2WI, and contrast-enhanced T1WI (CE-T1WI). Data normalization, dimensional reductions, feature selection, and classifications were performed using ten machine-learning classifiers. Four fusion models, namely T1WI + T2WI, T1WI + CE-T1WI, T2WI + CE-T1WI, and T1WI + T2WI + CE-T1WI, were constructed using the top ten features with the highest contribution in feature selection in the optimal models of T1WI, T2WI, and CE-T1WI. The Delong test compared areas under the curve (AUC) between models. RESULTS: The AUCs of training/validation/test1/test2 datasets for T1WI, T2WI, and CE-T1WI were 0.900/0.842/0.872/0.839, 0.876/0.789/0.842/0.863, and 0.899/0.824/0.831/0.707, respectively. The fusion model from T1WI + T2WI + CE-T1WI had the highest AUC. The AUCs of training/validation/test1/test2 datasets were 0.947/0.849/0.871/0.887. The T1WI + T2WI + CE-T1WI model demonstrated a significantly higher AUC than the T2WI + CE-T1WI model in both cohorts (p < 0.05) and outperformed the T2WI model in test 1 (p = 0.008) and the T1WI model in test 2 (p = 0.006). CONCLUSIONS: This fusion model based on radiomics from T1WI + T2WI + CE-T1WI images and machine learning can improve the power in predicting malignant sinonasal tumors with high accuracy, resilience, and robustness. CLINICAL RELEVANCE STATEMENT: Our study proposes a radiomics-based machine learning fusion model from T1- and T2-weighted images and contrast-enhanced T1-weighted images, which can non-invasively identify the nature of sinonasal tumors and improve the performance in predicting malignant sinonasal tumors. KEY POINTS: Differentiating benign and malignant sinonasal tumors is difficult due to similar clinical presentations. A radiomics model from T1 + T2 + contrast-enhanced T1 images can identify the nature of sinonasal tumors. This model can help distinguish benign and malignant sinonasal tumors.

6.
J Appl Microbiol ; 135(9)2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39152091

RESUMO

AIMS: To construct an efficient bacterial complex to degrade nicosulfuron and clarify its degradative characteristics, promote the growth of maize (Zea mays), and provide a theoretical foundation for the efficient remediation of soil contaminated with nicosulfuron. METHODS AND RESULTS: Biocompatibility was determined by the filter paper sheet method by mixing Serratia marcescens A1 and Bacillus cereus A2 in a 1:1 ratio, yielding A12. The optimum culture conditions for the bacterial composite were obtained based on a three-factor, three-level analysis using response surface methodology, with 29.25 g l-1 for maltodextrin, 10.04 g l-1 for yeast extract, and 19.93 g l-1 for NaCl, which resulted in 92.42% degradation at 4 d. The degradation characteristics of A12 were clarified as follows: temperature 30°C, pH 7, initial concentration of nicosulfuron 20 mg l-1, and 4% inoculum. The ability to promote growth was determined by measuring the ratio of the lysosphere diameter (D) to the colony diameter (d), and the ability of the complex A12 to promote growth was higher than that of the two single strains. CONCLUSIONS: Nicosulfuron degradation in sterilized and unsterilized soils reached 85.4% and 91.2% within 28 d, respectively. The ability of the strains to colonize the soil was determined by extraction of total soil DNA, primer design, and gel electrophoresis. The bioremediation effect of A12 was confirmed by the maximum recovery of fresh weight (124.35%) of nicosulfuron-sensitive crop plants and the significant recovery of soil enzyme activities, as measured by the physiological indices in the sensitive plants.


Assuntos
Bacillus cereus , Biodegradação Ambiental , Piridinas , Microbiologia do Solo , Poluentes do Solo , Compostos de Sulfonilureia , Compostos de Sulfonilureia/metabolismo , Poluentes do Solo/metabolismo , Piridinas/metabolismo , Bacillus cereus/metabolismo , Bacillus cereus/crescimento & desenvolvimento , Serratia marcescens/metabolismo , Serratia marcescens/crescimento & desenvolvimento , Zea mays/metabolismo , Zea mays/microbiologia , Solo/química , Herbicidas/metabolismo
7.
Neuroradiology ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39014270

RESUMO

PURPOSE: To evaluate nnU-net's performance in automatically segmenting and volumetrically measuring ocular adnexal lymphoma (OAL) on multi-sequence MRI. METHODS: We collected T1-weighted (T1), T2-weighted and T1-weighted contrast-enhanced images with/without fat saturation (T2_FS/T2_nFS, T1c_FS/T1c_nFS) of OAL from four institutions. Two radiologists manually annotated lesions as the ground truth using ITK-SNAP. A deep learning framework, nnU-net, was developed and trained using two models. Model 1 was trained on T1, T2, and T1c, while Model 2 was trained exclusively on T1 and T2. A 5-fold cross-validation was utilized in the training process. Segmentation performance was evaluated using the Dice similarity coefficient (DSC), sensitivity, and positive prediction value (PPV). Volumetric assessment was performed using Bland-Altman plots and Lin's concordance correlation coefficient (CCC). RESULTS: A total of 147 patients from one center were selected as training set and 33 patients from three centers were regarded as test set. For both Model 1 and 2, nnU-net demonstrated outstanding segmentation performance on T2_FS with DSC of 0.80-0.82, PPV of 84.5-86.1%, and sensitivity of 77.6-81.2%, respectively. Model 2 failed to detect 19 cases of T1c, whereas the DSC, PPV, and sensitivity for T1_nFS were 0.59, 91.2%, and 51.4%, respectively. Bland-Altman plots revealed minor tumor volume differences with 0.22-1.24 cm3 between nnU-net prediction and ground truth on T2_FS. The CCC were 0.96 and 0.93 in Model 1 and 2 for T2_FS images, respectively. CONCLUSION: The nnU-net offered excellent performance in automated segmentation and volumetric assessment in MRI of OAL, particularly on T2_FS images.

8.
Mol Ther ; 31(7): 1938-1959, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37002605

RESUMO

cGAS-STING signaling is a central component in the therapeutic action of most existing cancer therapies. The accumulated knowledge of tumor immunoregulatory network in recent years has spurred the development of cGAS-STING agonists for tumor treatment as an effective immunotherapeutic strategy. However, the clinical translation of these agonists is thus far unsatisfactory because of the low immunostimulatory efficacy and unrestricted side effects under clinically relevant conditions. Interestingly, the rational integration of biomaterial technology offers a promising approach to overcome these limitations for more effective and safer cGAS-STING-mediated tumor therapy. Herein, we first outline the cGAS-STING signaling axis and generally discuss its association with tumors. We then symmetrically summarize the recent progress in those biomaterial-based cGAS-STING agonism strategies to generate robust antitumor immunity, categorized by the chemical nature of those cGAS-STING stimulants and carrier substrates. Finally, a perspective is provided to discuss the existing challenges and potential opportunities in cGAS-STING modulation for tumor therapy.


Assuntos
Materiais Biocompatíveis , Excipientes , Imunidade Inata , Imunização , Nucleotidiltransferases/genética , Transdução de Sinais , Neoplasias/imunologia , Neoplasias/terapia , Antineoplásicos/imunologia
9.
Hum Brain Mapp ; 44(15): 5002-5012, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37539805

RESUMO

To explore the functional changes of the frontal eye field (FEF) and relevant brain regions and its role in the pathogenesis of intermittent exotropia (IXT) children via functional magnetic resonance imaging (fMRI). Twenty-four IXT children (mean age, 11.83 ± 1.93 years) and 28 normal control (NC) subjects (mean age, 11.11 ± 1.50 years) were recruited. During fMRI scans, the IXT children and NCs were provided with static visual stimuli (to evoke sensory fusion) and dynamic visual stimuli (to evoke motor fusion and vergence eye movements) with binocular disparity. Brain activation in the relevant brain regions and clinical characteristics were evaluated. Group differences of brain activation and brain-behavior correlations were investigated. For dynamic and static visual disparity relative to no visual disparity, reduced brain activation in the right FEF and right inferior occipital gyrus (IOG), and increased brain activation in the left middle temporal gyrus complex (MT+) were found in the IXT children compared with NCs. Significant positive correlations between the fusional vergence amplitude and the brain activation values were found in the right FEF, right IPL, and left cerebellum in the NC group. Positive correlations between brain activation values and Newcastle Control Scores (NCS) were found in the left MT+ in the IXT group. For dynamic visual disparity relative to static visual disparity, reduced brain activation in the right middle occipital gyrus, left cerebellum, and bilateral IPL was found in the IXT children compared with NCs. Significant positive correlations between brain activation values and the fusional vergence amplitude were found in the right FEF and right cerebellum in the NC group. Negative correlations between brain activation values and NCS were found in the right middle occipital gyrus, right cerebellum, left IPL, and right FEF in the IXT group. These results suggest that the reduced brain activation in the right FEF, left IPL, and cerebellum may play an important role in the pathogenesis of IXT by influencing fusional vergence function. While the increased brain activation in the left MT+ may compensate for this dysfunction in IXT children.


Assuntos
Exotropia , Lobo Frontal , Exotropia/diagnóstico por imagem , Exotropia/fisiopatologia , Humanos , Criança , Adolescente , Imageamento por Ressonância Magnética , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Mapeamento Encefálico
10.
Nat Mater ; 21(9): 1074-1080, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35668148

RESUMO

Electrostatic dielectric capacitors are essential components in advanced electronic and electrical power systems due to their ultrafast charging/discharging speed and high power density. A major challenge, however, is how to improve their energy densities to effectuate the next-generation applications that demand miniaturization and integration. Here, we report a high-entropy stabilized Bi2Ti2O7-based dielectric film that exhibits an energy density as high as 182 J cm-3 with an efficiency of 78% at an electric field of 6.35 MV cm-1. Our results reveal that regulating the atomic configurational entropy introduces favourable and stable microstructural features, including lattice distorted nano-crystalline grains and a disordered amorphous-like phase, which enhances the breakdown strength and reduces the polarization switching hysteresis, thus synergistically contributing to the energy storage performance. This high-entropy approach is expected to be widely applicable for the development of high-performance dielectrics.

11.
Fish Shellfish Immunol ; 137: 108781, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37127188

RESUMO

Peroxiredoxin (Prx), which is a newly discovered member of the antioxidant protein family, performs important biological functions in intracellular signal transduction. In the present study, a peroxiredoxin 4 gene was cloned from crayfish for the first time and named Pc-prx 4. According to the amino acid sequence signature, Pc-Prx 4 was identified as the typical 2-Cys Prx molecule, which possessed two conserved cysteines (Cys98 and Cys219). Time-course expression patterns post V. harveyi infection revealed that Pc-prx 4 was likely related to crayfish innate immune defense responses. In particular, the highest fold upregulation of the Pc-prx 4 mRNA transcript reached approximately 170 post V. harveyi infection in the crayfish hepatopancreas. The results of the mixed functional oxidase assay showed that rPc-Prx 4△ could resist the damaging effect of reactive oxygen species generated from the thiol/Fe3+/O2- reaction system to some extent. In addition, the results of the RNAi assay revealed that the crayfish survival rate was obviously increased post injection of V. harveyi when Pc-prx 4 was knocked down. Further study revealed that both hemolymph melanization and PO activity were strengthened to different degrees in the RNAi assay. Therefore, we speculated that the increase in the crayfish survival rate was likely due to the increase in hemolymph melanization. The obviously reinforced hemolymph melanization was directly caused by the upregulation of hemolymph PO activity, which was induced by the knockdown of Pc-prx 4. However, further studies are still indispensable for illuminating the molecular mechanism of Pc-prx 4 in the crayfish innate immune defense system.


Assuntos
Proteínas de Artrópodes , Astacoidea , Animais , Astacoidea/genética , Sequência de Aminoácidos , Imunidade Inata/genética , Peroxirredoxinas/genética , Clonagem Molecular
12.
Acta Oncol ; 62(12): 1757-1766, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37738252

RESUMO

BACKGROUND: Our previous study has revealed that EphA7 was upregulated in patient-derived esophageal squamous cell carcinoma (ESCC) xenografts with hyper-activated STAT3, but its mechanism was still unclear. MATERIALS AND METHODS: To assess the association between EphA7 and STAT3, western blotting, immunofluorescence, ChIP assay, and qRT-PCR were conducted. Truncated mutation and luciferase assay were performed to examine the promoter activity of EphA7. CCK-8 assay and colony formation were performed to assess the proliferation of ESCC. Cell-derived xenograft models were established to evaluate the effects of EphA7 on ESCC tumor growth. RNA-seq analyses were used to assess the effects of EphA7 on related signals. RESULTS: In this study, EphA7 was found upregulated in ESCC cell lines with high STAT3 activation, and immunofluorescence also showed that EphA7 was co-localized with phospho-STAT3 in ESCC cells. Interestingly, suppressing STAT3 activation by the STAT3 inhibitor Stattic markedly inhibited the protein expression of EphA7 in ESCC cells, in contrast, activation of STAT3 by IL-6 obviously upregulated the protein expression of EphA7. Moreover, the transcription of EphA7 was also mediated by the activation of STAT3 in ESCC cells, and the -2000∼-1500 region was identified as the key promoter of EphA7. Our results also indicated that EphA7 enhanced the cell proliferation of ESCC, and silence of EphA7 significantly suppressed ESCC tumor growth. Moreover, EphA7 silence markedly abolished STAT3 activation-derived cell proliferation of ESCC. Additionally, RNA-seq analyses indicated that several tumor-related signaling pathways were significantly changed after EphA7 downregulation in ESCC cells. CONCLUSION: Our results showed that the transcriptional expression of EphA7 was increased by activated STAT3, and the STAT3 signaling may act through EphA7 to promote the development of ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Receptor EphA7 , Fator de Transcrição STAT3 , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Receptor EphA7/metabolismo
13.
Int J Mol Sci ; 24(14)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37511309

RESUMO

Camellia oleifera a member of the family Theaceae, is a phosphorus (P) tolerator native to southern China. The SPX gene family critically regulates plant growth and development and maintains phosphate (Pi) homeostasis. However, the involvement of SPX genes in Pi signaling in Tea-Oil Camellia remains unknown. In this work, 20 SPX genes were identified and categorized into four subgroups. Conserved domains, motifs, gene structure, chromosomal location and gene duplication events were also investigated in the SPX gene family. Defense and stress responsiveness cis-elements were identified in the SPX gene promoters, which participated in low-Pi stress responses. Based on transcriptome data and qRT-PCR results, nine CoSPX genes had similar expression patterns and eight genes (except CoPHO1H3) were up-regulated at 30 days after exposure to low-Pi stress. CoSPX-MFS3 was selected as a key candidate gene by WGCNA analysis. CoSPX-MFS3 was a tonoplast protein. Overexpression of CoSPX-MFS3 in Arabidopsis promoted the accumulation of total P content and decreased the anthocyanin content. Overexpression of CoSPX-MFS3 could enhance low-Pi tolerance by increased biomass and organic acid contents in transgenic Arabidopsis lines. Furthermore, the expression patterns of seven phosphate starvation genes were higher in transgenic Arabidopsis than those in the wild type. These results highlight novel physiological roles of the SPX family genes in C. oleifera under low-Pi stress, and lays the foundation for a deeper knowledge of the response mechanism of C. oleifera to low-Pi stress.


Assuntos
Arabidopsis , Camellia , Camellia/genética , Camellia/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Plantas/metabolismo , Fosfatos/metabolismo , Chá , Regulação da Expressão Gênica de Plantas , Perfilação da Expressão Gênica
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(9): 1150-1154, 2023 Sep 10.
Artigo em Zh | MEDLINE | ID: mdl-37643964

RESUMO

OBJECTIVE: To analyze the clinical phenotype and genetic characteristics of a patient with Alport syndrome. METHODS: A patient with Alport syndrome who had visited the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the patient were collected. High-throughput sequencing was carried out to detect potential variant of the COL4A3, COL4A4 and COL4A5 genes, and Sanger sequencing was carried out for verification of candidate variants in the family. RESULTS: The main clinical manifestations of the patient included hematuria, proteinuria, and impaired hearing. Audiometric testing suggested symmetrical cochlear sensory neural hearing loss on both sides. Renal biopsy revealed mild mesangial proliferative glomerulonephritis. Genetic testing revealed that the patient has harbored compound heterozygous variants of the COL4A4 gene, namely c.940G>A (p.Gly314Ser) and c.3773G>A (p.Gly1258Asp), which were respectively inherited from her father and mother. Neither variant has been reported before, and were predicted to be pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION: The c.940G>A (p.Gly314Ser) and c.3773G>A (p.Gly1258Asp) compound heterozygous variants of the COL4A4 gene probably underlay the Alport syndrome in this patient. Above finding has enriched the mutational spectrum of the COL4A4 gene.


Assuntos
Nefrite Hereditária , Feminino , Humanos , Nefrite Hereditária/genética , Hematúria , Testes Genéticos , Genômica , Audição , Colágeno Tipo IV/genética
15.
Psychol Med ; 52(11): 2052-2061, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33121546

RESUMO

BACKGROUND: Major depressive disorder (MDD) is a common debilitating disorder characterized by impaired spontaneous brain activity, yet little is known about its alterations in dynamic properties and the molecular mechanisms associated with these changes. METHODS: Based on the resting-state functional MRI data of 65 first-episode, treatment-naïve patients with MDD and 66 healthy controls, we compared dynamic regional homogeneity (dReHo) of spontaneous brain activity between the two groups, and we investigated gene expression profiles associated with dReHo alterations in MDD by leveraging transcriptional data from the Allen Human Brain Atlas and weighted gene co-expression network analysis. RESULTS: Compared with healthy controls, patients with MDD consistently showed reduced dReHo in both fusiform gyri and in the right temporal pole and hippocampus. The expression profiles of 16 gene modules were correlated with dReHo alterations in MDD. These gene modules were enriched for various biological process terms, including immune, synaptic signalling, ion channels, mitochondrial function and protein metabolism, and were preferentially expressed in different cell types. CONCLUSIONS: Patients with MDD have reduced dReHo in brain areas associated with emotional and cognitive regulation, and these changes may be related to complex polygenetic and polypathway mechanisms.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/genética , Mapeamento Encefálico , Transcriptoma , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética
16.
Gen Physiol Biophys ; 41(1): 43-51, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35253649

RESUMO

Inflammatory bowel disease (IBD) is a common chronic inflammatory gastrointestinal disease. The therapeutic strategies of IBD are limited. IBD mouse models were established by administering 4% dextran sodium sulfate (DSS), which were further treated with Leonurine (7.5, 15, 30 mg/kg). The disease phenotypes, cell apoptosis, inflammation factors and oxidative stress related chemicals were evaluated. In addition, the potential related mechanism was also explored. Consequently, Leonurine ameliorated IBD-associated disease phenotypes and increase colon lengths and inhibited intestinal cell apoptosis in DSS-induced IBD mice. In addition, Leonurine reduced the expression of inflammation factors and oxidative stress level in DSS-induced IBD mice. Finally, Leonurine inhibited TLR4/NF-κB signaling pathway and activated of Nrf2/HO-1 signaling pathway. Leonurine can ameliorate IBD-induced apoptosis, inflammation response and oxidative stress via the activation of Nrf2/HO-1 signaling pathway and suppression of TLR4/ NF-κB pathway.


Assuntos
Anti-Inflamatórios , Doenças Inflamatórias Intestinais , Animais , Anti-Inflamatórios/farmacologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Ácido Gálico/análogos & derivados , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Sulfatos
17.
Int J Mol Sci ; 23(6)2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35328341

RESUMO

The ethylene-responsive element (AP2/ERF) is one of the keys and conserved transcription factors (TFs) in plants that play a vital role in regulating plant growth, development, and stress response. A total of 202 AP2/ERF genes were identified from the pecan genome and renamed according to the chromosomal distribution of the CiAP2/ERF genes. They were divided into four subfamilies according to the domain and phylogenetic analysis, including 26 AP2, 168 ERF, six RAV, and two Soloist gene family members. These genes were distributed randomly across the 16 chromosomes, and we found 19 tandem and 146 segmental duplications which arose from ancient duplication events. The gene structure and conserved motif analysis demonstrated the conserved nature of intron/exon organization and motifs among the AP2/ERF genes. Several cis-regulatory elements, which were related to light responsiveness, stress, and defense responses, were identified in the promoter regions of AP2/ERFs. The expression profiling of 202 CiAP2/ERF genes was assessed by using RNA-Seq data and qRT-PCR during development (pistillate flowering development, graft union development, and kernel development) and under abiotic stresses (waterlogging, drought). Moreover, the results suggested that the ERF-VII members may play a critical role in waterlogging stress. These findings provided new insights into AP2/ERF gene evolution and divergence in pecan and can be considered a valuable resource for further functional validation, as well as for utilization in a stress-resistance-variety development program.


Assuntos
Carya , Carya/genética , Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética
18.
Small ; 17(9): e1903663, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31729163

RESUMO

Bismuth ferrite (BiFeO3 ) has recently become interesting as a room-temperature multiferroic material, and a variety of prototype devices have been designed based on its thin films. A low-cost and simple processing technique for large-area and high-quality BiFeO3 thin films that is compatible with current semiconductor technologies is therefore urgently needed. Development of BiFeO3 thin films is summarized with a specific focus on the chemical solution route. By a systematic analysis of the recent progress in chemical-route-derived BiFeO3 thin films, the challenges of these films are highlighted. An all-solution chemical-solution deposition (AS-CSD) for BiFeO3 thin films with different orientation epitaxial on various oxide bottom electrodes is introduced and a comprehensive study of the growth, structure, and ferroelectric properties of these films is provided. A facile low-cost route to prepare large-area high-quality epitaxial BFO thin films with a comprehensive understanding of the film thickness, stoichiometry, crystal orientation, ferroelectric properties, and bottom electrode effects on evolutions of microstructures is provided. This work paves the way for the fabrication of devices based on BiFeO3 thin films.

19.
Am J Otolaryngol ; 42(3): 102900, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33454455

RESUMO

OBJECTIVE: To investigate the distribution of pathogenic bacteria in patients with tympanic membrane perforation after chronic suppurative otitis media (CSOM) in dry ear and its influence on the success rate of tympanoplasty and postoperative infection. METHODS: 740 patients with tympanic membrane perforation after CSOM underwent endoscopic tympanoplasty were selected. The mucosal surface secretion of middle-ear was collected for bacterial culture and drug sensitivity test. The patients were followed up several times from 1 week to 3 months after the surgery. RESULTS: 740 cases of ear secretions samples, raise the pathogens of 208 cases (28.1%), the success rate of surgery with microorganism grown and with no grown was 93.8% and 91.5%. fungus (14.6%) was the most species among the patients with the positive result, followed by methicillin-sensitive Staphylococcus aureus (4.1%), Pseudomonas (2.0%), Staphylococcus epidermidis (1.9%), methicillin-resistant Staphylococcus aureus (1.6%) and so on. There was no statistical difference in the proportion of perforation and infection in each group. There were no statistically significant differences in gender, age and duration of disease among the groups. CONCLUSION: There were still microbial colonization in patients with tympanic membrane perforation after CSOM in dry ear, include fungus, Staphylococcus aureus and Pseudomonas aeruginosa. Different microbial colonization had no influence on the success rate of tympanoplasty and postoperative infection.


Assuntos
Orelha Média/microbiologia , Endoscopia/métodos , Otite Média Supurativa/complicações , Otite Média Supurativa/microbiologia , Perfuração da Membrana Timpânica/microbiologia , Perfuração da Membrana Timpânica/cirurgia , Timpanoplastia/métodos , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Pseudomonas/isolamento & purificação , Estudos Retrospectivos , Staphylococcus aureus/isolamento & purificação , Staphylococcus epidermidis/isolamento & purificação , Perfuração da Membrana Timpânica/etiologia
20.
Pharm Res ; 37(6): 102, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32440783

RESUMO

PURPOSE: To model absolute neutrophil count (ANC) suppression in response to acute radiation (AR) exposure and evaluate ANC time course as a predictor of overall survival (OS) in response to AR exposure with or without treatment with granulocyte colony-stimulating factor in nonhuman primates. METHODS: Source data were obtained from two pivotal studies conducted in rhesus macaques exposed to 750 cGy of whole body irradiation on day 0 that received either placebo, daily filgrastim, or pegfilgrastim (days 1 and 8 after irradiation). Animals were observed for 60 days with ANC measured every 1 to 2 days. The population model of ANC response to AR and the link between observed ANC time course and OS consisted of three submodels characterizing injury due to radiation, granulopoiesis, and a time-to-event model of OS. RESULTS: The ANC response model accurately described the effects of AR exposure on the duration of neutropenia. ANC was a valid surrogate for survival because it explained 76% (95% CI, 41%-97%) and 73.2% (95% CI, 38.7%-99.9%) of the treatment effect for filgrastim and pegfilgrastim, respectively. CONCLUSION: The current model linking radiation injury to neutropenia and ANC time course to OS can be used as a basis for translating these effects to humans.


Assuntos
Filgrastim/administração & dosagem , Modelos Biológicos , Neutropenia/prevenção & controle , Neutrófilos , Polietilenoglicóis/administração & dosagem , Lesões Experimentais por Radiação/prevenção & controle , Animais , Estudos de Viabilidade , Feminino , Contagem de Leucócitos , Leucopoese/efeitos dos fármacos , Leucopoese/efeitos da radiação , Macaca mulatta , Masculino , Neutropenia/sangue , Neutropenia/etiologia , Neutropenia/mortalidade , Lesões Experimentais por Radiação/sangue , Lesões Experimentais por Radiação/mortalidade , Fatores de Tempo
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