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1.
Plant Cell ; 36(7): 2689-2708, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38581430

RESUMO

Lateral branches are important components of shoot architecture and directly affect crop yield and production cost. Although sporadic studies have implicated abscisic acid (ABA) biosynthesis in axillary bud outgrowth, the function of ABA catabolism and its upstream regulators in shoot branching remain elusive. Here, we showed that the MADS-box transcription factor AGAMOUS-LIKE 16 (CsAGL16) is a positive regulator of axillary bud outgrowth in cucumber (Cucumis sativus). Functional disruption of CsAGL16 led to reduced bud outgrowth, whereas overexpression of CsAGL16 resulted in enhanced branching. CsAGL16 directly binds to the promoter of the ABA 8'-hydroxylase gene CsCYP707A4 and promotes its expression. Loss of CsCYP707A4 function inhibited axillary bud outgrowth and increased ABA levels. Elevated expression of CsCYP707A4 or treatment with an ABA biosynthesis inhibitor largely rescued the Csagl16 mutant phenotype. Moreover, cucumber General Regulatory Factor 1 (CsGRF1) interacts with CsAGL16 and antagonizes CsAGL16-mediated CsCYP707A4 activation. Disruption of CsGRF1 resulted in elongated branches and decreased ABA levels in the axillary buds. The Csagl16 Csgrf1 double mutant exhibited a branching phenotype resembling that of the Csagl16 single mutant. Therefore, our data suggest that the CsAGL16-CsGRF1 module regulates axillary bud outgrowth via CsCYP707A4-mediated ABA catabolism in cucumber. Our findings provide a strategy to manipulate ABA levels in axillary buds during crop breeding to produce desirable branching phenotypes.


Assuntos
Ácido Abscísico , Cucumis sativus , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/genética , Cucumis sativus/metabolismo , Ácido Abscísico/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Brotos de Planta/genética , Reguladores de Crescimento de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Plantas Geneticamente Modificadas , Sistema Enzimático do Citocromo P-450
2.
Plant Cell ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39133577

RESUMO

Complete disruption of critical genes is generally accompanied by severe growth and developmental defects, which dramatically hinder its utilization in crop breeding. Identifying subtle changes, such as single nucleotide polymorphisms (SNPs), in critical genes that specifically modulate a favorable trait is a prerequisite to fulfill breeding potential. Here, we found two SNPs in the E-class floral organ identity gene cucumber (Cucumis sativus) SEPALLATA2 (CsSEP2) that specifically regulate fruit length. Haplotype (HAP) 1 (8G2667A) and HAP2 (8G2667T) exist in natural populations, whereas HAP3 (8A2667T) is induced by ethyl methanesulfonate mutagenesis. Phenotypic characterization of four near-isogenic lines and a mutant line showed that HAP2 fruits are significantly longer than those of HAP1, and those of HAP3 are 37.8% longer than HAP2 fruit. The increasing fruit length in HAP1-3 was caused by a decreasing inhibitory effect on CRABS CLAW (CsCRC) transcription (a reported positive regulator of fruit length), resultinged in enhanced cell expansion. Moreover, a 7638G/A-SNP in melon (Cucumis melo) CmSEP2 modulates fruit length in a natural melon population via the conserved SEP2-CRC module. Our findings provide a strategy for utilizing essential regulators with pleiotropic effects during crop breeding.

3.
BMC Biol ; 22(1): 203, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39256728

RESUMO

BACKGROUND: Mutations occurring in nucleic acids or proteins may affect the binding affinities of protein-nucleic acid interactions. Although many efforts have been devoted to the impact of protein mutations, few computational studies have addressed the effect of nucleic acid mutations and explored whether the identical methodology could be applied to the prediction of binding affinity changes caused by these two mutation types. RESULTS: Here, we developed a generalized algorithm named PNBACE for both DNA and protein mutations. We first demonstrated that DNA mutations could induce varying degrees of changes in binding affinity from multiple perspectives. We then designed a group of energy-based topological features based on different energy networks, which were combined with our previous partition-based energy features to construct individual prediction models through feature selections. Furthermore, we created an ensemble model by integrating the outputs of individual models using a differential evolution algorithm. In addition to predicting the impact of single-point mutations, PNBACE could predict the influence of multiple-point mutations and identify mutations significantly reducing binding affinities. Extensive comparisons indicated that PNBACE largely performed better than existing methods on both regression and classification tasks. CONCLUSIONS: PNBACE is an effective method for estimating the binding affinity changes of protein-nucleic acid complexes induced by DNA or protein mutations, therefore improving our understanding of the interactions between proteins and DNA/RNA.


Assuntos
Algoritmos , DNA , Mutação , Ligação Proteica , DNA/metabolismo , Biologia Computacional/métodos , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética
4.
Small ; 20(25): e2309171, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38196296

RESUMO

Various natural polymers offer sustainable alternatives to petroleum-based adhesives, enabling the creation of high-performance engineered materials. However, additional chemical modifications and complicated manufacturing procedures remain unavoidable. Here, a sustainable high-performance engineered composite that benefits from bonding strategies with multiple energy dissipation mechanisms dominated by chemical adhesion and mechanical interlocking is demonstrated via the fungal smart creative platform. Chemical adhesion is predominantly facilitated by the extracellular polymeric substrates and glycosylated proteins present in the fungal outer cell walls. The dynamic feature of non-covalent interactions represented by hydrogen bonding endows the composite with extensive unique properties including healing, recyclability, and scalable manufacturing. Mechanical interlocking involves multiple mycelial networks (elastic modulus of 2.8 GPa) binding substrates, and the fungal inner wall skeleton composed of chitin and ß-glucan imparts product stability. The physicochemical properties of composite (modulus of elasticity of 1455.3 MPa, internal bond strength of 0.55 MPa, hardness of 82.8, and contact angle of 110.2°) are comparable or even superior to those of engineered lignocellulosic materials created using petroleum-based polymers or bioadhesives. High-performance composite biofabrication using fungi may inspire the creation of other sustainable engineered materials with the assistance of the extraordinary capabilities of living organisms.


Assuntos
Fungos , Quitina/química , Módulo de Elasticidade
5.
Langmuir ; 40(17): 9120-9133, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38629900

RESUMO

Nanostructured activated carbon (AC) adsorbents derived from woody biomass have garnered attention for their potential usage to remove toxic substances from the environment due to their high specific surface area, superior micro/mesoporosity, and tunable surface chemistry profile. However, chemical dopants widely used to enhance the chemical reactivity with heavy metals would pollute the environment and conflict with the vision of a cleaner and sustainable environment. Herein, we report a facile, green, and sustainable approach using fungi modification combined with alkali activation to produce AC for heavy metal removal. The decayed wood-derived AC (DAC) exhibited a high specific surface area of 2098 m2/g, and the content of O and N functional groups was 18 and 2.24%, respectively. It showed remarkable adsorption capacity toward Cd2+ of 148.7 mg/g, which was much higher than most reported Cd2+ adsorbents. Such excellent adsorption capacity was primarily based on enhanced physical adsorption (pore filling, π-π) and chemical adsorption (functional group complexation, ion exchange, and precipitation). Additionally, the DAC showed rapid kinetics and remarkable applicability in both dynamic environments and actual water samples. These results suggest that decayed wood has excellent potential for efficient use in the removal of Cd2+ from wastewater. Furthermore, these results indicate that decayed wood can be cleanly produced into high efficiency heavy metal adsorbents to realize value-added utilization of decayed wood.

6.
Angew Chem Int Ed Engl ; : e202413927, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304910

RESUMO

Introducing fluorinated electrolyte additives to construct LiF-rich solid-electrolyte interphase (SEI) on Si-based anodes is proven an effective strategy for coping with its massive volume changes during cycling. However, most current research on fluorine-containing additives focuses on their thermodynamics of decomposition, lacking studies on the correlation between the molecular structure of additives and their decomposition kinetics. Herein, two fluorinated ester additives, diethyl fluoromalonate (F1DEM) and diethyl 2,2-difluoromalonate (F2DEM) were designed and synthesized. Through combining a wealth of characterizations and simulations, it is revealed that despite the similar reduction thermodynamics, the favorable reduction kinetics of single-fluorinated F1DEM facilitate a LiF-rich layer during the early stage of SEI formation, contributing to the formation of a more robust SEI on SiOx anode compared to the difluorinated F2DEM. Consequently, the proposed additive achieves excellent cycling stability (84 % capacity retention after 1000 cycles) for 5 Ah 21700 cylindrical batteries under practical testing conditions. By unveiling the role of reaction kinetics, a long-overlooked aspect for the study of electrolyte additives, this work sheds light on how to construct a stable SEI on Si-based anodes.

7.
Mol Biol Rep ; 50(1): 399-408, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36336778

RESUMO

BackgroundInorganic mercury is a well-known toxic substance that can cause oxidative stress and liver damage. Luteolin (Lut) is a kind of natural antioxidant, which is widely found in plants. Therefore, we focused on exploring the alleviative effect of Lut on liver injury induced by mercuric chloride (HgCl2), and the potential molecular mechanism of eliminating mercury ions in quails.Methods and resultsTwenty-one-day-old male quails were randomly split into four groups: control group, Lut group, HgCl2 group, and HgCl2 + Lut group. The test period was 12 weeks. The results showed that Lut could significantly ameliorate oxidative stress, the release of inflammatory factors, and liver damage caused by HgCl2, and reduce the accumulation of Hg2+ in quail liver. Furthermore, Lut evidently increased the levels of protein kinase C α (PKCα), nuclear factor-erythroid-2-related factor 2 (Nrf2), and its downstream proteins, and inhibited nuclear factor-kappaB (NF-κB) production in the liver of quails treated by HgCl2.ConclusionsTo sum up, our results suggest that Lut not only reduces the levels of oxidative stress and inflammation, but also promotes the excretion of Hg2+ by promoting the PKCα/Nrf2 signaling pathway to alleviate HgCl2-induced liver injury in quails.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Mercúrio , Humanos , Luteolina/farmacologia , Proteína Quinase C-alfa/metabolismo , Proteína Quinase C-alfa/farmacologia , Mercúrio/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo
8.
Appl Opt ; 62(10): D125-D130, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37132777

RESUMO

Natural compound eyes inspire the development of artificial optical devices that feature a large field of view and fast motion detection. However, the imaging of artificial compound eyes dramatically depends on many microlenses. The single focal length of the microlens array significantly limits the actual applications of artificial optical devices, like distinguishing objects at different distances. In this study, a curved artificial compound eye for a microlens array with different focal lengths was fabricated by inkjet printing and air-assisted deformation. By adjusting the space of the microlens array, secondary microlenses were created between intervals of the primary microlens. The diameter/height of the primary and secondary microlens arrays are 75/25 µm and 30/9 µm, respectively. The planar-distributed microlens array was transformed into a curved configuration using air-assisted deformation. Compared with adjusting the curved base to distinguish objects at different distances, the reported technique features simplicity and is easy to operate. The applied air pressure can be used to tune the field of view of the artificial compound eye. The microlens arrays with different focal lengths could distinguish the objects at different distances without additional components. When the external objects move a small distance, they can be detected by the microlens arrays due to their different focal lengths. It could effectively improve the motion perception of the optical system. Moreover, the focusing and imaging performances of the fabricated artificial compound eye were further tested. The compound eye combines the advantages of monocular eyes and compound eyes, holding great potential for developing advanced optical devices with a large field of view and automatic variable-focus imaging.

9.
BMC Health Serv Res ; 23(1): 151, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36782193

RESUMO

BACKGROUND: In response to an aging population, the Chinese government implemented the three-child policy in 2021 based on the comprehensive two-child policy. With the implementation of the new birth policy, people's maternal and child health (MCH) needs will also increase. The allocation and fairness of MCH human resources directly affect people's access to MCH services. The purpose of this study is to analyze the allocation of health human resources in Chinese maternal and child health care institutions, evaluate the fairness of the allocation, to provide a reference for the rational allocation of MCH human resources. METHODS: The data of health technicians, licensed (assistant) physicians, and registered nurses in maternal and child health care institutions nationwide from 2016 to 2020 were included. The health resource density index (HRDI) is used to evaluate the allocation level of MCH human resources. The Gini coefficient (G) and Theil index (T) are used to evaluate the fairness of the allocation of MCH human resources from the perspectives of population and geographic area. RESULTS: From 2016 to 2020, the average annual growth rate of the number of health technicians, licensed (assistant) physicians, and registered nurses in Chinese maternal and child health care institutions was 7.53, 6.88, and 9.12%, respectively. The Gini coefficient (G) of the three types of MCH human resources allocated by population were all below 0.23, and the Gini coefficient (G) allocated by geographical area were all above 0.65. The Theil index (T) of the three types of MCH human resources allocated by population was all lower than 0.06, and the Theil index (T) allocated by geographical area was all higher than 0.53. In addition, the three types of MCH human resources allocated by population and geographic area contributed more than 84% of the Theil index within the group (Tintra) to the Theil index (T). CONCLUSIONS: China's MCH human resources were fair in terms of population allocation, but unfair in terms of geographical area allocation. In the future, more attention should be paid to the geographical accessibility of MCH human resources, and the allocation of resources should comprehensively consider the two factors of serving the population and geographical area.


Assuntos
Saúde da Criança , Atenção à Saúde , Feminino , Criança , Humanos , Idoso , Estudos Longitudinais , Mão de Obra em Saúde , Recursos em Saúde , China , Alocação de Recursos
10.
BMC Plant Biol ; 20(1): 390, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32842963

RESUMO

BACKGROUND: Bud dormancy is a strategic mechanism plants developed as an adaptation to unfavorable environments. The grapevine (Vitis vinifera) is one of the most ancient fruit vine species and vines are planted all over the world due to their great economic benefits. To better understand the molecular mechanisms underlying bud dormancy between adjacent months, the transcriptomes of 'Rosario Bianco' grape buds of 6 months and three nodes were analyzed using RNA-sequencing technology and pair-wise comparison. From November to April of the following year, pairwise comparisons were conducted between adjacent months. RESULTS: A total of 11,647 differentially expressed genes (DEGs) were obtained from five comparisons. According to the results of cluster analysis of the DEG profiles and the climatic status of the sampling period, the 6 months were divided into three key processes (November to January, January to March, and March to April). Pair-wise comparisons of DEG profiles of adjacent months and three main dormancy processes showed that the whole grapevine bud dormancy period was mainly regulated by the antioxidant system, secondary metabolism, cell cycle and division, cell wall metabolism, and carbohydrates metabolism. Additionally, several DEGs, such as VvGA2OX6 and VvSS3, showed temporally and spatially differential expression patterns, which normalized to a similar trend during or before April. CONCLUSION: Considering these results, the molecular mechanisms underlying bud dormancy in the grapevine can be hypothesized, which lays the foundation for further research.


Assuntos
Flores/genética , Flores/fisiologia , Dormência de Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/fisiologia , Vitis/genética , Vitis/metabolismo , China , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Estações do Ano , Análise de Sequência de RNA , Transcriptoma
11.
Opt Express ; 27(21): 29534-29546, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684213

RESUMO

In a pulse pump Rb atomic magnetometer, the magnetic field is associated with the Larmor frequency of the free induction decay (FID) signal. The reconstruction of the magnetic field from the collected signal, thereby, is crucial for magnetocardiography. In this study, we propose a backward singular value decomposition (BSVD) method for fast reconstruction of a magnetocardiographic signal. Experiments on the simulated and real data were performed to estimate its potential advantages over previous approaches, such as the fast Fourier transform (FFT) method, the zero-crossing means (ZM) method, etc. The results show the high accuracy of the BSVD method compared with other methods. More importantly, the BSVD method requires less sampled data than other methods while ensuring the accuracy. With the help of it, the recording time can be greatly reduced from the initial 3.6m s to the present 0.6m s. Thus, the time resolution of the magnetocardiograph could reach 2m s which is equivalent to that of conventional electrocardiogragh. This will bring the atomic magnetocardiography more practicable in clinic application.

12.
Mol Carcinog ; 56(2): 447-463, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27253463

RESUMO

The enhancer of zeste homolog 2 (EZH2) is involved in a number of fundamental pathological processes of cancer. However, its role in DNA repair pathway is still unclear. Here, we have identified XPA as a novel target gene of EZH2 via a DNA repair pathway PCR array. XPA plays a pivot role in nucleotide excision repair (NER). The expression of XPA was significantly increased by EZH2 specific inhibitor GSK126 or lentiviral shEZH2 in nasopharyngeal carcinoma (NPC) CNE and 8F cell lines. Chromatin immunoprecipitation assay demonstrated that EZH2 catalyzes H3K27 trimethylation at the XPA promoters. Furthermore, we validated the negative correlation of EZH2 and XPA in a NPC tissue microarray by immunohistochemistry staining. We also found that high expression of EZH2 was positively correlated with advanced T, N, and AJCC stage of NPC; and low expression of XPA was positively correlated with advanced T and N stage. In NPC cell lines, increased XPA expression by EZH2 inhibition resulted in a more rapid removal of UVC induced 6-4PP- and CPD-DNA adducts, as well as enhanced efficiency of DNA repair after UVC irradiation as detected by the Comet assay and immunofluorescence staining of γH2Ax. Consistently, increased cell clonogenic survival, decreased apoptosis, and necrosis after UVC irradiation, and increased resistance to DNA damaging agent cisplatin was also observed in EZH2 inhibited cells. These results illustrate that EZH2 may promote carcinogenesis and cancer development of NPC by transcriptional repression of XPA gene and inactivation of NER pathway. © 2016 Wiley Periodicals, Inc.


Assuntos
Carcinoma/genética , Carcinoma/patologia , Reparo do DNA , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Nasofaringe/patologia , Proteína de Xeroderma Pigmentoso Grupo A/genética , Antineoplásicos/farmacologia , Carcinoma/tratamento farmacológico , Carcinoma/metabolismo , Linhagem Celular Tumoral , Cisplatino/farmacologia , Regulação para Baixo , Proteína Potenciadora do Homólogo 2 de Zeste/análise , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Código das Histonas , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Nasofaringe/efeitos dos fármacos , Nasofaringe/metabolismo , Regiões Promotoras Genéticas , Proteína de Xeroderma Pigmentoso Grupo A/análise , Proteína de Xeroderma Pigmentoso Grupo A/metabolismo
13.
Acta Biochim Biophys Sin (Shanghai) ; 48(3): 229-37, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26849897

RESUMO

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors with poor prognosis and recurrence in South China. The hard eradication of NPC in clinic is predominantly due to cancer stem cells (CSCs). Increasing evidence revealed that the aberrant activation of Wnt/ß-catenin was positively correlated with the produce of CSCs. To further investigate the effect of ß-catenin on CSCs and tumorigenesis in NPC, a CNE2 cell line (pLKO.1-sh-ß-catenin-CNE2) with stably suppressed expression of ß-catenin was used in this study. The expressions of biomarkers in CSCs including c-myc, Nanog, Oct3/4, Sox2, EpCAM as well as adhesion-related proteins like E-cadherin and vimentin were analyzed by western blot analysis and immunofluorescent staining. The proliferation and migration abilities were investigated by MTT assay and Transwell assay, respectively. Cell cycle was analyzed by flow cytometry. Finally, xenograft was performed to determine the effect of ß-catenin on oncogenesis in vivo. Results showed that the expressions of c-myc, Nanog, Oct3/4, Sox2, and EpCAM were all decreased in pLKO.1-sh-ß-catenin-CNE2 cells. It was also found that vimentin was downregulated, while E-cadherin was upregulated. Results of MTT and Transwell assays suggested that the proliferation and migration abilities were impaired by silencing of ß-catenin, and more cells were arrested in G1 phase when compared with the control. In vivo study indicated that the tumor growth was markedly suppressed in experimental group. Based on current findings, ß-catenin may function as an essential protein for the maintenance of migration and proliferation abilities of NPC cells, and a complicated network consisting of c-myc, Nanog, Oct3/4, Sox2, EpCAM, E-cadherin, vimentin, and ß-catenin may be involved in the inherent regulation mechanisms.


Assuntos
Neoplasias Nasofaríngeas/patologia , Células-Tronco Neoplásicas/patologia , beta Catenina/fisiologia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Inativação Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , beta Catenina/genética
14.
Clin Lab ; 61(9): 1331-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26554254

RESUMO

BACKGROUND: The relationship between microRNA-1 (miR-1) expression and prognosis has not been reported in hepatocellular carcinoma (HCC). The present study aimed to explore the clinicopathological significance and the prognostic role of miR-1 in HCC. METHODS: The expression levels of miR-1 were quantified using real-time quantitative PCR (q-PCR) in 40 surgically resected HCC samples and matched adjacent non-cancerous tissues. RESULTS: MiR-1 expression was significantly downregulated in HCC compared with matched non-cancerous tissues. Aberrant miR-1 expression was significantly correlated with gender, expression of hepatitis B virus surface antigen (HBsAg), tumor differentiation, vein invasion, and TNM stage. Patients with low expression of miR-1 had significantly reduced overall survival compared with patients with high expression of miR-1 (p = 0.04).The multivariate Cox regression analysis indicated that miR-1 expression (HR = 2.79; p = 0.005), gender (HR = 0.087; p = 0.005), vein invasion (HR = 0.172; p = 0.007), and TNM stage (HR = 3.421; p = 0.001) were independent prognostic factors for overall survival. CONCLUSIONS: Low miR-1 expression is associated with shortened survival time. MiR-1 may act as a potential prognostic biomarker for HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/biossíntese , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , China/epidemiologia , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B/sangue , Humanos , Estimativa de Kaplan-Meier , Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real , alfa-Fetoproteínas/análise
15.
Blood ; 119(25): 6043-51, 2012 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-22442351

RESUMO

Complement inhibitors expressed on tumor cells provide an evasion mechanism against mAb therapy and may modulate the development of an acquired antitumor immune response. Here we investigate a strategy to amplify mAb-targeted complement activation on a tumor cell, independent of a requirement to target and block complement inhibitor expression or function, which is difficult to achieve in vivo. We constructed a murine fusion protein, CR2Fc, and demonstrated that the protein targets to C3 activation products deposited on a tumor cell by a specific mAb, and amplifies mAb-dependent complement activation and tumor cell lysis in vitro. In syngeneic models of metastatic lymphoma (EL4) and melanoma (B16), CR2Fc significantly enhanced the outcome of mAb therapy. Subsequent studies using the EL4 model with various genetically modified mice and macrophage-depleted mice revealed that CR2Fc enhanced the therapeutic effect of mAb therapy via both macrophage-dependent FcγR-mediated antibody-dependent cellular cytotoxicity, and by direct complement-mediated lysis. Complement activation products can also modulate adaptive immunity, but we found no evidence that either mAb or CR2Fc treatment had any effect on an antitumor humoral or cellular immune response. CR2Fc represents a potential adjuvant treatment to increase the effectiveness of mAb therapy of cancer.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Inativadores do Complemento/administração & dosagem , Neoplasias/terapia , Animais , Anticorpos Monoclonais/química , Inativadores do Complemento/química , Proteínas do Sistema Complemento/metabolismo , Proteínas do Sistema Complemento/fisiologia , Modelos Animais de Doenças , Imunoconjugados/química , Imunoconjugados/uso terapêutico , Imunoglobulina G/administração & dosagem , Imunoglobulina G/química , Imunoterapia/métodos , Linfoma/tratamento farmacológico , Linfoma/patologia , Linfoma/terapia , Masculino , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Melanoma Experimental/terapia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Terapia de Alvo Molecular , Metástase Neoplásica , Neoplasias/patologia , Receptores de Complemento 3d/administração & dosagem , Receptores de Complemento 3d/química , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
16.
Autophagy ; : 1-2, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38991544

RESUMO

In the budding yeast Saccharomyces cerevisiae, macroautophagy/autophagy can be induced by various types of starvation. It is thought that potential autophagic substrates vary to meet specific nutritional demands under different starvation conditions. In a recent study, Gross et al. found that autophagy induced by phosphate starvation includes many selective aspects. For example, this work identified Pho81 as a regulator of pexophagy under conditions of phosphate starvation. Pho81 senses phosphate metabolites and directly interacts with Atg11 to promote Atg1-mediated Atg11 phosphorylation. This finding provides an example of how modulation of the Atg1/ULK kinase complex can convey specific metabolic information to regulate autophagic substrates.Abbreviation: AKC: Atg1/ULK kinase complex.

17.
Autophagy ; 20(6): 1211-1212, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38456639

RESUMO

Golgiphagy is a selective form of macroautophagy, characterized by the targeted degradation of Golgi compartments through specific receptors. In two recent studies, the YIPF3-YIPF4 heterodimer has been independently identified as the first Golgiphagy receptor within mammalian cells. This heterodimeric complex exhibits a direct affinity for mammalian Atg8-family proteins (ATG8s), thereby facilitating the expansion of phagophores in proximity to Golgi regions. Notably, the interaction between YIPF3-YIPF4 heterodimers and ATG8s undergoes regulatory modulation through phosphorylation. Furthermore, cells lacking either YIPF3 or YIPF4 display defects in Golgiphagy. To elucidate the physiological relevance of these proteins, the necessity of YIPF3-YIPF4 in orchestrating Golgi proteome remodeling was substantiated through experimentation in an in vitro neuronal differentiation model.Abbreviation: ATG: autophagy related; ATG8s: mammalian Atg8-family proteins; LIR, LC3-interacting region.


Assuntos
Autofagia , Complexo de Golgi , Animais , Humanos , Autofagia/fisiologia , Complexo de Golgi/metabolismo , Multimerização Proteica
18.
Int J Biol Macromol ; 279(Pt 4): 135473, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39250985

RESUMO

Medical nonwovens fabrics are pivotal materials in modern healthcare systems, and find extensively application in surgical gowns, masks, nursing pads, and surgical instrument packaging. As healthcare requirements evolve and medical technology advances, the demand for functional nonwoven medical devices is continuously increasing. In addition, numerous environmental challenges and the need to transition to a sustainable society have increased the popularity of studies on environmentally friendly multifunctional nonwoven materials prepared from biomass fibers. Therefore, in this study, ecofriendly bamboo fibers were used to fabricate multifunctional medical nonwoven materials with superhydrophobic, antibacterial, flame-retardant, and biocompatible properties. Specifically, ZIF-67 was grown in situ on natural bamboo cellulose fibers (BCFs) extracted from natural bamboo and coated with polydimethylsiloxane to construct an environmentally friendly and versatile nonwoven fabric. The treated nonwoven fabric exhibited superhydrophobicity with contact angle of 163° and possess excellent self-cleaning properties. The antibacterial activity of the samples was investigated by the plate-counting method; the results showed that the untreated BCFs did not exhibit antibacterial activity, whereas the treated bamboo nonwoven fabrics demonstrated significant antibacterial activity (p < 0.001), with an antibacterial rate of >99 % against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, and Candida albicans. In addition, when the samples were exposed to different temperatures (-4 and 50 °C) and humidities (0 % and 95 %), they demonstrated an antibacterial activity of >99 % against E. coli (F5,10 = 0.602; p = 0.670) and S. aureus (F4,10 = 0.289; p = 0.879). The heat release rate and smoke production rate of the nonwoven fabric decreased by 54.64 % and 93.18 %, respectively, compared to those of the BCFs, indicating excellent flame retardancy. The nonwoven fabric also exhibited satisfactory biocompatibility and breathability, ensuring user comfortability. This research not only has significant implications for producing low-cost, environmentally friendly, sustainable, and multifunctional medical products and openi up new pathways for the diversified utilization of bamboo, thereby expanding its applicability.

19.
Heliyon ; 10(18): e37892, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39323857

RESUMO

Jingdong 120-meter radio telescope (JRT) is poised to become the world's largest single-aperture fully steerable medium-low frequency radio telescope. However, like other large-aperture radio telescopes, the JRT is vulnerable to wind loads, which can cause structural deformation and pointing errors. Addressing this challenge requires the ability to predict dynamic winds in real-time. This study developed a wind pressure preprocessing and prediction model using sensor data collected from the Kunming 40-meter radio telescope (KRT), enabling real-time prediction of wind pressure on the telescope. The model employs adaptive noise and Variational Mode Decomposition (VMD) techniques to eliminate random noise from the original wind pressure data. Subsequently, wind pressure predictions are made using a Bidirectional Long Short-term Memory (BiLSTM) model. By conducting predictions under various stabilization conditions and conducting a thorough analysis of measurement data from five sensors, the study has achieved impressive results in predicting wind pressure on the KRT reflector surface. The proposed model demonstrates the lowest MAE, RMSE, and MAPE, while achieving the highest R 2 across various data sets. Where the average R 2 of the proposed model is 0.9392 at 45° pitch angle attitude and the RMSE, MAE and MAPE values are 1.4923, 1.2377 and 1.82% respectively. This model helps wind load monitoring of real-time wind pressure monitoring of the telescope surface, to study the effects of wind load on pointing accuracy. By adjusting the control parameters to reduce wind load interference, to ensure the high-precision work of a large radio telescope, such as JRT.

20.
Materials (Basel) ; 17(18)2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39336271

RESUMO

The durability of concrete materials in harsh environmental conditions, particularly in cold regions, has garnered significant attention in civil engineering research in recent years. Concrete structures in these areas are often damaged by the combined effects of alkali-silica reaction (ASR) and freeze-thaw cycles, leading to structural cracks and significant safety hazards. Numerous studies have demonstrated that polypropylene fiber concrete exhibits excellent crack resistance and durability, making it promising for applications in cold regions. This study elucidates the impact of alkali content on concrete durability by comparing the mechanical properties and durability of different alkali-aggregate concretes. The principal experimental methodologies employed include freeze-thaw cycle experiments, which examine patterns of mass loss; fluctuations in the dynamic modulus of elasticity; and changes in mechanical properties before and after freeze cycles. The findings indicate that increased alkali content in concrete reduces its strength and durability. At 100% alkali-aggregate content, compressive strength decreases by 35.5%, flexural strength by 32.9%, mass loss increases by 35.85%, relative dynamic elastic modulus by 39.4%, and residual strength by 97.28%, indicating higher alkali content leads to diminished durability. Additionally, this paper introduces a constitutive damage model, validated by a strong correlation with experimental stress-strain curves, to effectively depict the stress-strain relationship of concrete under varying alkali contents. This research contributes to a broader understanding of concrete durability in cold climates and guides the selection of materials for sustainable construction in such environments.

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