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1.
J Chem Inf Model ; 64(5): 1502-1511, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38413369

RESUMO

Protein function prediction is essential for disease treatment and drug development; yet, traditional biological experimental methods are less efficient in annotating protein function, and existing automated methods fail to fully leverage protein multisource data. Here, we present MSF-PFP, a computational framework that fuses multisource data features to predict protein function with high accuracy. Our framework designs specific models for feature extraction based on the characteristics of various data sources, including a global-local-individual strategy for local location features. MSF-PFP then integrates extracted features through a multisource feature fusion model, ultimately categorizing protein functions. Experimental results demonstrate that MSF-PFP outperforms eight state-of-the-art models, achieving FMax scores of 0.542, 0.675, and 0.624 for the biological process (BP), molecular function (MF), and cellular component (CC), respectively. The source code and data set for MSF-PFP are available at https://swanhub.co/TianGua/MSF-PFP, facilitating further exploration and validation of the proposed framework. This study highlights the potential of multisource data fusion in enhancing protein function prediction, contributing to improved disease therapy and medication discovery strategies.


Assuntos
Proteínas , Software
2.
BMC Genomics ; 24(1): 660, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919661

RESUMO

BACKGROUND: Milk production traits are complex traits with vital economic importance in the camel industry. However, the genetic mechanisms regulating milk production traits in camels remain poorly understood. Therefore, we aimed to identify candidate genes and metabolic pathways that affect milk production traits in Bactrian camels. METHODS: We classified camels (fourth parity) as low- or high-yield, examined pregnant camels using B-mode ultrasonography, observed the microscopic changes in the mammary gland using hematoxylin and eosin (HE) staining, and used RNA sequencing to identify differentially expressed genes (DEGs) and pathways. RESULTS: The average standard milk yield over the 300 days during parity was recorded as 470.18 ± 9.75 and 978.34 ± 3.80 kg in low- and high-performance camels, respectively. Nine female Junggar Bactrian camels were subjected to transcriptome sequencing, and 609 and 393 DEGs were identified in the low-yield vs. high-yield (WDL vs. WGH) and pregnancy versus colostrum period (RSQ vs. CRQ) comparison groups, respectively. The DEGs were compared with genes associated with milk production traits in the Animal Quantitative Trait Loci database and in Alashan Bactrian camels, and 65 and 46 overlapping candidate genes were obtained, respectively. Functional enrichment and protein-protein interaction network analyses of the DEGs and candidate genes were conducted. After comparing our results with those of other livestock studies, we identified 16 signaling pathways and 27 core candidate genes associated with maternal parturition, estrogen regulation, initiation of lactation, and milk production traits. The pathways suggest that emerged milk production involves the regulation of multiple complex metabolic and cellular developmental processes in camels. Finally, the RNA sequencing results were validated using quantitative real-time PCR; the 15 selected genes exhibited consistent expression changes. CONCLUSIONS: This study identified DEGs and metabolic pathways affecting maternal parturition and milk production traits. The results provides a theoretical foundation for further research on the molecular mechanism of genes related to milk production traits in camels. Furthermore, these findings will help improve breeding strategies to achieve the desired milk yield in camels.


Assuntos
Camelus , Leite , Animais , Gravidez , Feminino , Camelus/genética , Lactação/genética , Parto , Perfilação da Expressão Gênica
3.
BMC Plant Biol ; 23(1): 656, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114925

RESUMO

AIMS: In-depth studies on plant ion uptake and plant growth-promoting rhizobacteria (PGPR) at the molecular level will help to further reveal the effects of PGPR on plants and their interaction mechanisms under salt stress. METHODS: Cotton was inoculated with a PGPR-Enterobacter cloacae Rs-35, and the ion uptake capacity, membrane transporter protein activity, and expression of key genes were determined under salt stress. Changes in the endogenous hormone content of cotton were also determined. Further, the genome-wide metabolic pathway annotation of E. cloacae Rs-35 and its differential enrichment pathway analysis of multi-omics under salinity environments were performed. RESULTS: In a pot experiment of saline-alkali soil, E. cloacae Rs-35-treated cotton significantly increased its uptake of K+ and Ca2+ and decreased uptake of Na+, elevated the activity of the H+-ATPase, and increased the sensitivity of the Na+/H+ reverse transporter protein on the vesicle membrane. Meanwhile, inoculation with E. cloacae Rs-35 could promote cotton to maintain the indole-3-acetic acid (IAA) content under salt stress. Genome-wide annotation showed that E. cloacae Rs-35 was respectively annotated to 31, 38, and 130 related genes in osmotic stress, phytohormone and organic acid metabolism, and ion uptake metabolic pathway. Multi-omics differences analysis showed that E. cloacae Rs-35 were enriched to tryptophan metabolism, multiple amino acid biosynthesis, carbon and glucose synthesis, and oxidative phosphorylation metabolic pathways at the transcriptome, proteome, and metabolome. CONCLUSION: E. cloacae Rs-35 can promote cotton balance cell ion concentration, stabilize intracellular IAA changes, stimulate induction of systemic tolerance, and promote the growth of cotton plants under salt stress.


Assuntos
Enterobacter cloacae , Gossypium , Enterobacter cloacae/metabolismo , Gossypium/genética , Gossypium/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Desenvolvimento Vegetal , Estresse Salino
4.
BMC Genomics ; 23(1): 37, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996356

RESUMO

BACKGROUND: Advances in DNA sequencing technologies have transformed our capacity to perform life science research, decipher the dynamics of complex soil microbial communities and exploit them for plant disease management. However, soil is a complex conglomerate, which makes functional metagenomics studies very challenging. RESULTS: Metagenomes were assembled by long-read (PacBio, PB), short-read (Illumina, IL), and mixture of PB and IL (PI) sequencing of soil DNA samples were compared. Ortholog analyses and functional annotation revealed that the PI approach significantly increased the contig length of the metagenomic sequences compared to IL and enlarged the gene pool compared to PB. The PI approach also offered comparable or higher species abundance than either PB or IL alone, and showed significant advantages for studying natural product biosynthetic genes in the soil microbiomes. CONCLUSION: Our results provide an effective strategy for combining long and short-read DNA sequencing data to explore and distill the maximum information out of soil metagenomics.


Assuntos
Metagenoma , Solo , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Análise de Sequência de DNA
5.
BMC Vet Res ; 18(1): 360, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36171581

RESUMO

BACKGROUND: In camels, nasopharyngeal myiasis is caused by the larvae of Cephalopina titillator, which parasitize the tissues of nasal and paranasal sinuses, pharynx, and larynx. C. titillator infestation adversely affects the health of camels and decreases milk and meat production and even death. However, the C. titillator infestation in Bactrian camels has not been widely studied. METHODS: The present study was conducted to determine the prevalence and risk factors of C. titillator in Bactrian camels of northwestern Xinjiang. Suspected larvae recovered from infested camels were evaluated for C. titillator by microscopy and polymerase chain reaction. Nucleotide sequences of the partial mitochondrial cytochrome c oxidase subunit I (COX1) and cytochrome b (CYTB) genes from the C. titillator of camels were aligned from the NCBI database. Furthermore, the gross and histopathological alterations associated with C. titillator infestation were evaluated via pathological examination. RESULTS: Of 1263 camels examined 685 (54.2%) camels were infested with suspected C. titillator larvae. Different larval stages were topically detected in the nasal passages and pharynx of the camel heads. Microscopy analysis of the pharyngeal mucosa tissue revealed necrotic tissue debris and some inflammatory cells. Molecular detection of the larval COX1 and CYTB genes indicated that pathogen collected in Bactrian camels was C. titillator. The epidemiological study demonstrated that the prevalence rate of C.titillator infestation was significantly higher in camels of Bestierek Town Pasture (67.2%) and Karamagai Town Pasture (63.6%) compared to Kitagel Town Pasture (38.7%) and Qibal Town Pasture (35.8%) (P < 0.05). No significant difference was observed between the prevalence rates in male (52.6%) and female (54.6%) camels (P > 0.05). The prevalence was higher in warm (64.2%) than that in cold (48.4%) seasons (P < 0.001). The prevalence in camels with non-nomadic method (67.2%) was significantly higher than in animals with nomadic method (47.5%) (P < 0.001). The prevalence of C.titillator infestation was significantly higher in animals of aged 5-10 (60.1%) and aged > 10 (61.1%) years old compared to those of aged < 5 (31.7%) years old camels (P < 0.001). CONCLUSION: Our results confirm that there is a high prevalence of C. titillator in Bactrian camels from Xinjiang, closely related to age, season, pasture environment, and husbandry methods. Developing prevention, diagnosis, and control programs to prevent transmission is necessary.


Assuntos
Dípteros , Miíase , Animais , Camelus , China/epidemiologia , Citocromos b , Complexo IV da Cadeia de Transporte de Elétrons , Feminino , Larva , Masculino , Miíase/epidemiologia , Miíase/veterinária , Prevalência
6.
Fish Shellfish Immunol ; 54: 153-63, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26497095

RESUMO

In this study, Litopenaeus vannamei was injected with double-stranded RNA (dsRNA) against L. vannamei immunoglobulin heavy chain binding protein (LvBip) to activating UPR in the hemocytes, shirmps injected dsRNA against enhanced green fluorescence protein (eGFP) as control group. And genes expression in hemocytes of then were analyzed using Illumina Hiseq 2500 (PE100). By comparing the analyzed results, 1418 unigenes were significantly upregulated, and 596 unigenes were significantly down-regulated upon UPR. Analysis of the differentially expressed genes against known databases indicated that the distribution of gene pathways between the upregulated and down-regulated genes were substantially different. A total of 208 genes of UPR system were obtained, and 69 of them were differentially expressed between the two groups. Results also showed that L. vannamei UPR was involved in various metabolic processes, such as glycometabolism, lipid metabolism, amino acid metabolism, and nucleic acid metabolism. In addition, UPR was emgaged in immune-assicoated signaling pathways, such as NF-κB signaling pathway, NOD-like receptor signaling pathway, Hippo signaling pathway, p38 MAPK signaling pathway and Wnt signaling pathway in L. vannamei. These results improved our current understanding of the L. vannamei UPR, and highlighted its importance in cell homeostasis upon environmental stress.


Assuntos
Regulação da Expressão Gênica , Penaeidae/fisiologia , Resposta a Proteínas não Dobradas , Animais , Proteínas de Artrópodes , Perfilação da Expressão Gênica , Hemócitos/metabolismo , Penaeidae/genética , Penaeidae/imunologia , Penaeidae/microbiologia , Transcriptoma
7.
Fish Shellfish Immunol ; 54: 144-52, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26481519

RESUMO

A mitochondrial specific stress response termed mitochondrial unfolded protein response (UPR(mt)) is activated in responding to disturbance of protein homeostasis in mitochondria. The activating transcription factor associated with stress-1 (designated as ATFS-1) is the key regulator of UPR(mt). To investigating the roles of ATFS-1 (LvATFS-1) in Litopenaeus vannamei mitochondrial stress remission and immunity, it's full length cDNA was cloned. The open reading frame of LvATFS-1 was 1, 557 bp in length, deducing to a 268 amino acids protein. LvATFS-1 was highly expressed in muscle, hemocytes and eyestalk. Subcellular location assays showed that N-terminal of LvATFS-1 contained a mitochondrial targeting sequence, which could directed the fused EGFP located to mitochondria. And the C-terminal of LvATFS-1, which had a nuclear localization signal, expressed in nucleus. The in vitro experiments verified that LvATFS-1 could reduced the level of intracellular reactive oxygen species (ROS). And results of real-time RT-PCR indicated that LvATFS-1 might scavenge excess ROS via ROS-eliminating genes regulation. Reporter gene assays showed that LvATFS-1 could upregulated the expression of the antimicrobial peptide genes in Drosophila Schneider 2 cells. Results of real-time RT-PCR showed that Vibrio alginolyticus or white spot syndrome virus (WSSV) infection induced the expression of LvATFS-1. And knocked-down LvATFS-1 by RNAi resulted in a higher cumulative mortality of L. vannamei upon V. alginolyticus or WSSV infection. These results suggested that LvATFS-1 not only rolled in mitochondrial specific stress responding, but also important for L. vannamei immunologic defence.


Assuntos
Fatores Ativadores da Transcrição/genética , Penaeidae/fisiologia , Fatores Ativadores da Transcrição/química , Fatores Ativadores da Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Regulação da Expressão Gênica , Especificidade de Órgãos , Penaeidae/genética , Penaeidae/imunologia , Penaeidae/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Resposta a Proteínas não Dobradas , Vibrio alginolyticus/fisiologia , Vírus da Síndrome da Mancha Branca 1/fisiologia
8.
Fish Shellfish Immunol ; 50: 109-16, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26806164

RESUMO

Apoptosis signal-regulating kinase 1 (ASK1), a mitogen-activated protein kinase kinase kinase, is crucial in various cellular responses. In the present study, we identified and characterized an ASK1 homolog from Litopenaeus vannamei (LvASK1). The full-length cDNA of LvASK1 was 5400 bp long, with an open reading frame encoding a putative 1420 amino acid protein. LvASK1 was highly expressed in muscle, hemocyte, eyestalk and heart. Real-time RT-PCR analysis showed that the expression of the LvASK1 was upregulated during the white spot syndrome virus (WSSV) challenge. The knocked-down expression of LvASK1 by RNA interference significantly reduced the apoptotic ratio of the hemocytes collected from WSSV-infected L. vannamei. Furthermore, the down-regulation of LvASK1 also decreased the cumulative mortality of WSSV-infected L. vannamei. These results suggested that down-regulation of LvASK1 decreased the apoptotic rate of hemocytes in WSSV-infected shrimp, and that it could contribute to the reduction of cumulative mortality in WSSV-infected L. vannamei.


Assuntos
Apoptose , Proteínas de Artrópodes/genética , Regulação da Expressão Gênica , MAP Quinase Quinase Quinase 5/genética , Penaeidae/fisiologia , Vírus da Síndrome da Mancha Branca 1/fisiologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/metabolismo , Sequência de Bases , Hemócitos/fisiologia , MAP Quinase Quinase Quinase 5/química , MAP Quinase Quinase Quinase 5/metabolismo , Penaeidae/genética , Penaeidae/imunologia , Penaeidae/virologia , Filogenia , Alinhamento de Sequência/veterinária
9.
Fish Shellfish Immunol ; 41(2): 147-55, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25172110

RESUMO

Members of activating transcription factor/cyclic adenosine 3', 5'-monophosphate response element binding protein (ATF/CREB) family are induced by various stress signals and function as effector molecules. Consequently, cellular changes occur in response to discrete sets of instructions. In this work, we found an ATF transcription factor in Litopenaeus vannamei designated as LvATFß. The full-length cDNA of LvATFß was 1388 bp long with an open reading frame of 939 bp that encoded a putative 313 amino acid protein. The protein contained a basic region-leucine zipper (bZip) domain that was a common feature among ATF/CREB transcription factors. LvATFß was highly expressed in intestines, gills, and heart. LvATFß expression was dramatically upregulated by white spot syndrome virus (WSSV) infection. Pull-down assay revealed that LvATFß had strong affinity to promoters of WSSV genes, namely, wsv059 and wsv166. Dual-luciferase reporter assay showed that LvATFß could upregulate the expression of wsv059 and wsv166. Knocked down LvATFß resulted in decreased expression of wsv059 and wsv166 in WSSV-challenged L. vannamei. Knocked down expression of wsv059 and wsv166 by RNA interference inhibited the replication and reduce the mortality of L. vannamei during WSSV challenge inoculation. The copy numbers of WSSV in wsv059 and wsv166 knocked down group were significant lower than in the control. These results suggested that LvATFß may be involved in WSSV replication by regulating the expression of wsv059 and wsv166.


Assuntos
Fatores Ativadores da Transcrição/genética , Regulação da Expressão Gênica/fisiologia , Penaeidae/genética , Penaeidae/virologia , Replicação Viral/genética , Vírus da Síndrome da Mancha Branca 1 , Fatores Ativadores da Transcrição/metabolismo , Animais , Clonagem Molecular , DNA Complementar/genética , Técnicas de Silenciamento de Genes , Brânquias/metabolismo , Mucosa Intestinal/metabolismo , Luciferases , Miocárdio/metabolismo , Fases de Leitura Aberta/genética , Interferência de RNA
10.
Plants (Basel) ; 13(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38931076

RESUMO

The impact of climates on the radial growth of muti-species remains insufficiently understood in the climate-sensitive southeastern Tibetan Plateau, and this hampers an effective assessment of forest growth under the background of global warming. Here, we studied the growth-climate relationships of three major species (Abies georgei, Larix potaninii, and Picea likiangensis) on the Baima Snow Mountain (BSM) by using dendrochronology methods. We constructed basal area increment (BAI) residual chronologies based on the dated ring-width measurements and correlated the chronologies with four climate factors. We also calculated the contributions of each climate factor to species growth. We found that photothermal conditions played a more important role than moisture in modulating radial growth, and P. likiangensi presented the strongest sensitivity to climate change among the three species. The growing season (June and July) temperature positively affected the radial growth of three species. Winter (previous December and current January) SD negatively impacted the tree growth of A. georgei and P. likiangensis. Significant correlations between growth and precipitation were detected only in A. georgei (January and May). Warming since the beginning of the 1950s promoted the growth of A. georgei and P. likiangensis, while the same effect on L. potaninii growth was found in the recent 50 years.

11.
Food Chem X ; 22: 101281, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38544935

RESUMO

In this study, a rapid, inexpensive, and accurate colorimetric sensor for detecting psychrophilic bacteria was designed, comprising gold (Au) nanoparticles (NPs) modified by d-amino acid (D-AA) as color-metric probes. Based on the aggregation of Au NPs induced by psychrophilic bacteria, a noticeable color shift occurred within 6 h. Depending on the various metabolic behaviors of bacteria to different D-AA, four primary psychrophilic bacteria in raw milk were successfully distinguished by learning the response patterns. Furthermore, the quantification of single bacteria and the practical application in milk samples could be realized. Notably, a rapid colorimetric method was constructed by combining Au/D-AA with antibiotics for the minimum inhibitory concentration of psychrophilic bacteria, which relied on differences in bacteria metabolic activity in response to diverse antibiotic treatments. Therefore, the method enables the rapid detection and susceptibility evaluation of psychrophilic bacteria, promoting clinical practicability and antibiotic management.

12.
Synth Syst Biotechnol ; 9(4): 793-808, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39072145

RESUMO

Microorganisms, particularly extremophiles, have evolved multiple adaptation mechanisms to address diverse stress conditions during survival in unique environments. Their responses to environmental coercion decide not only survival in severe conditions but are also an essential factor determining bioproduction performance. The design of robust cell factories should take the balance of their growing and bioproduction into account. Thus, mining and redesigning stress-tolerance elements to optimize the performance of cell factories under various extreme conditions is necessary. Here, we reviewed several stress-tolerance elements, including acid-tolerant elements, saline-alkali-resistant elements, thermotolerant elements, antioxidant elements, and so on, providing potential materials for the construction of cell factories and the development of synthetic biology. Strategies for mining and redesigning stress-tolerance elements were also discussed. Moreover, several applications of stress-tolerance elements were provided, and perspectives and discussions for potential strategies for screening stress-tolerance elements were made.

13.
Microbiol Spectr ; : e0023224, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38912811

RESUMO

Soil salinization usually occurs in arid and semi-arid climate areas from 37 to 50 degrees north latitude and 73 to 123 degrees east longitude. These regions are inhabited by a large number of Coleopteran insects, which play an important role in the ecological cycle. However, little is known about the endosymbiotic microbial taxa and their biological characteristics in these insects. A study of endosymbiotic microorganisms of Coleoptera from Xinjiang, a typical arid and inland saline area, revealed that endosymbiont bacteria with salinity tolerance are common among the endosymbionts of Coleoptera. Functional prediction of the microbiota analysis indicated a higher abundance of inorganic ion transporters and metabolism in these endosymbiont strains. Screening was conducted on the tolerable 11% NaCl levels of Brevibacterium casei G20 (PRJNA754761), and differential metabolite and proteins were performed. The differential metabolites of the strain during the exponential and plateau phases were found to include benzene compounds, organic acids, and their derivatives. These results suggest that the endosymbiotic microorganisms of Coleoptera in this environment have adaptive evolution to extreme environments, and this group of microorganisms is also one of the important resources for mining saline and alkaline-tolerant chassis microorganisms and high-robustness enzymes. IMPORTANCE: Coleoptera insects, as the first largest order of insect class, have the characteristics of a wide variety and wide distribution. The arid and semi-arid climate makes it more adaptable. By studying the endosymbiont bacteria of Coleoptera insects, we can systematically understand the adaptability of endosymbiont bacteria to host and special environment. Through the analysis of endosymbiont bacteria of Coleoptera insects in different saline-alkali areas in arid and semi-arid regions of Xinjiang, it was found that bacteria in different host samples were resistant to saline-alkali stress. These results suggest that bacteria and their hosts co-evolved in response to this climate. Therefore, this study is of great significance for understanding the endosymbiont bacteria of Coleoptera insects and obtaining extremophile resources (Saline-alkali-resistant chassis strains with modification potential for the production of bulk chemicals and highly robust industrial enzymes).

14.
Sci Total Environ ; 918: 170607, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38336057

RESUMO

Plant overcompensatory growth (OCG) is an important mechanism by which plant communities adapt to environmental disturbance. However, it is not clear whether plant OCG can occur in degraded alpine meadows. Here, we conducted a mowing experiment in an alpine meadow at three degradation levels (i.e., severe degradation, SD; moderate degradation, MD; and light degradation, LD) on the southeastern Qinghai-Tibetan Plateau from 2018 to 2020 to investigate plant OCG and its relationships with soil available nutrients, plant nutrient use efficiency (i.e., nitrogen use efficiency, NUE; and phosphorus use efficiency, PUE), and precipitation. The results showed that 1) the OCG of the plant community generally occurred across all degradation levels, and the OCG strength of the plant community decreased with mowing duration. Moreover, the OCG strength of the plant community in the SD treatment was significantly greater than that in the MD and LD treatments after two years of mowing (p < 0.05). 2) In LD and MD, the soil nitrate nitrogen (NO3-) and available phosphorus (AP) concentrations exhibited a decreasing trend (p < 0.05), while the soil ammonium nitrogen (NH4+) concentration did not change from 2018 to 2020 (p > 0.05). In the SD treatment, the soil NO3- concentration tended to decrease (p < 0.05), the NH4+ concentration tended to increase (p < 0.05), and the AP concentration exhibited an inverse parabolic trend (p < 0.05) from 2018 to 2020. 3) From 2018 to 2020, plant NUE and PUE exhibited decreasing trends at all degradation levels. 4) Plant nutrient use efficiency, which is regulated by complex plant-soil interactions, strongly controlled the OCG of the plant community along each degradation gradient. Moreover, precipitation not only directly promoted the OCG of the plant community but also indirectly affected it by regulating the structure of the plant community and plant nutrient use efficiency. These results suggest that the OCG of the plant community in degraded alpine meadows may benefit not only from the strong self-regulating capacity of the plant-soil system but also from humid climatic conditions.


Assuntos
Pradaria , Plantas , Tibet , Plantas/metabolismo , Nitrogênio/análise , Solo/química , Fósforo/metabolismo
15.
Front Oncol ; 13: 1211759, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576888

RESUMO

OX40 (CD134), a member of the TNF receptor superfamily, is a widely studied costimulatory immune checkpoint. Several OX40 agonistic antibodies are in the clinical stage for cancer treatment, among which PF-04518600 is the leader and currently in phase II trial. It has been recognized that one potential mode of action for anti-OX40 antibodies is the deletion of intratumoral Tregs. Thus, a novel human anti-OX40 antibody, BAT6026, was generated with enhanced antibody dependent cellular cytotoxicity (ADCC) via fucose deletion to strengthen its Treg depletion activity. This characteristic of BAT6026 differentiates it from other previously reported anti-OX40 antibodies in the field of tumor therapy. The affinity of BT6026 to OX40 was 0.28nM, approximately 8 times stronger than that of PF-04518600. BAT6026 effectively competed for the binding of ligand OX40L to OX40, whereas PF-04518600 only partially competed. Moreover, compared to PF-04518600, BAT6026 activated T cells more effectively when clustered by FcγRs engagement and stimulated SEB-pretreated PBMCs to secrete IL-2 cytokines in vitro. In addition, BAT6026 demonstrated stronger anti-tumor activity than PF-04518600 in an OX40-humanized mouse MC38 tumor model. BAT6026 also showed a significantly synergistic effect on tumor inhibition when combined treatment with PD-1 antibody. Analysis of tumor-infiltrating T cells revealed that BAT6026 treatment significantly reduced Treg cells and increased CD8+ T cells in tumor. Preclinical safety assessment in non-human primates demonstrated a good safety profile for BAT6026. Together these data warrant further development of BAT6026 into clinical trials for patients with cancer.

16.
World J Microbiol Biotechnol ; 28(6): 2383-93, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22806112

RESUMO

A plant growth-promoting rhizobacterial strain Rs-2 with 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity was isolated from salinized soils using ACC as the sole nitrogen source. Based on its physiological and biochemical properties and 16S rDNA sequence analysis, this strain was identified as Raoultella planticola. The maximum value of nitrogen fixation, dissolved phosphorus and dissolved potassium of Rs-2 were 148.8 µg/ml, 205.0 and 4.31 mg/l, respectively within 192 h liquid culture. The germination rate of cotton seeds (Gossypium hirsutum L.) inoculated with Rs-2 (Rs-2-S) was enhanced by 29.5 % in pot experiments compared with that of the control (CK-S). Subsequently, individual plant height, fresh weight and dry weight of cotton seedlings in Rs-2-S treatment increased by 15.0, 33.7 and 33.3 %, respectively, compared with those in CK-S treatment. Statistical analysis showed that the inoculums of Rs-2 promoted significantly (P < 0.05) cotton growth. Further analysis showed that Rs-2 reduced the quantities of ethylene and abscisic acid in cotton seedlings, and increased indole acetic acid content in cotton seedlings under salinity stress. The accumulation of N, P, K(+), Ca(2+) and Fe(2+) in the cotton plants was increased significantly (P < 0.05) in Rs-2-S treatment, whereas the uptake of Na(+) in cotton seedlings decreased (P < 0.05). Hence, the present observations suggested that R. planticola Rs-2 could have a promising potential for promoting cotton growth and alleviating salinity stress.


Assuntos
Carbono-Carbono Liases/metabolismo , Enterobacteriaceae/enzimologia , Gossypium/crescimento & desenvolvimento , Gossypium/microbiologia , Carbono-Carbono Liases/genética , Enterobacteriaceae/fisiologia , Salinidade , Microbiologia do Solo
17.
Front Plant Sci ; 13: 822594, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185988

RESUMO

The allocation pattern of plant biomass presents the strategy of the plant community to adopt environmental changes, while the driver of biomass allocation is still unclear in degraded alpine grassland ecosystems. To explore the issue, this study investigated the shoot-to-root (R/S) ratio, plant aboveground traits, and root competition of three functional groups (i.e., grasses, sedges, and forbs) at three degradation levels (i.e., no obvious degradation, ND; moderate degradation, MD; and severe degradation, SD) in an alpine meadow in the eastern Qinghai-Tibetan Plateau. The relationships among plant aboveground traits, root competition, and R/S ratio were tested using the structural equation model (SEM). The results showed that the shoot and root biomass tended to decrease, but the R/S ratio of the plant community did not change along the degradation gradient. Plant height, lateral spread, and leaf length of most plant functional groups reduced, while leaf width and leaf area of most plant functional groups did not change along the degradation gradients. The root competition ability (presented as the fraction of root biomass in total biomass) of sedges in MD was the lowest, while that of grasses was the highest. The effects of aboveground competition on the R/S ratio were non-linear because of the different roles of plant height, lateral spread, and leaf area in regulating the R/S ratio along the degradation gradient. In contrast, the effects of belowground competition on the R/S ratio were linear because belowground competition promoted the R/S ratio, and the strength of this effect reduced along the degradation gradient. These results indicate that plant competition might be a critical factor to maintain the high R/S ratio in degraded alpine meadows.

18.
Food Funct ; 13(1): 255-269, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34897341

RESUMO

This research investigated the effects of camel whey protein (CWP) treatment on type 2 diabetes mellitus (T2DM) rats and insulin resistance (IR) HepG2 cell models. Body weight and fasting blood glucose were observed in type 2 diabetes mellitus (T2DM) rats every week, and biochemical parameters in serum samples were evaluated after 6 weeks. Antioxidant activity in the liver was estimated, and histological examination of the liver tissues was conducted. After CWP treatment, the glucose uptake and lipid accumulation were examined in insulin-resistant HepG2 cells. Our results indicated that CWP mitigated the body weight loss, reversed dyslipidemia, and inhibited the inflammatory response, in T2DM rats. Meanwhile, it protected the liver from being injured by reducing the level of oxidative stress. In the CWP group, the pathological changes were significantly reduced, while the liver lobule structure, liver cell arrangement, as well as congestion, edema, and vacuolization were improved. Our results from quantitative real-time PCR and western blot analyses showed that CWP could up-regulate the expression levels of insulin receptor substrate-2 (IRS-2), phosphoinositide3-kinase (PI3K), protein kinase B (AKT), and glycogen synthase (GS). An active protein component CWP8 was isolated and identified, which was shown to be able to stimulate glycogen synthesis and ameliorate lipid accumulation in IR HepG2 cells. These data indicate that CWP and CWP8 might act as potential natural products regulating glucose and lipid metabolism in T2DM.


Assuntos
Camelus , Complicações do Diabetes/metabolismo , Hepatopatias/metabolismo , Fígado/efeitos dos fármacos , Proteínas do Soro do Leite/farmacologia , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Células Hep G2 , Humanos , Resistência à Insulina/genética , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
19.
Microbiol Spectr ; 10(3): e0050022, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35587636

RESUMO

Populus euphratica Oliv. has a high tolerance for drought, salinity, and alkalinity. The main purpose of this study is to explore the effects of environments of different salinity intensities on endophytic community structure and the possible roles of endophytes in the tolerance of host plants. The characterization of endogenous bacteria in diversity has been investigated by using the Illumina high-throughput sequencing technique. The research showed that endophytic bacteria of P. euphratica in an extremely saline environment had low species diversity, especially in sap tissue. The dominant phyla in all groups were Proteobacteria, Actinobacteria, and Bacteroidetes. Notably, Firmicutes (relative abundance >5%) was a different dominant phylum in the samples from the high-saline environment compared with the relatively low-saline-environment group. The linear discriminant analysis effect size (LEfSe) analysis found that there were significant differences in different saline environments of Cytophagaceae (family), Rhodobacteraceae (family), and Rhodobacterales (order). These results indicated that the composition of the endogenous bacterial community was related to the growth environment of host plants. The predictive analysis of KEGG pathways and enzymes showed that the abundance of some enzymes and metabolic pathways of endophytes of P. euphratica increased with the increase of soil salinity, and most of the enzymes were related to energy metabolism and carbohydrate metabolism. These findings suggested that the endogenous bacteria of the host plant had different expression mechanisms under different degrees of stress, and this mechanism was very obvious in the distribution of endophytes, while the function of the endogenous bacteria needs to be further explored. IMPORTANCE Euphrates poplar (Populus euphratica Oliv.), as the only tree species that grows in the desert, has tenacious vitality with the characteristics of cold tolerance, drought tolerance, salt-alkali tolerance, and wind-sand resistance. P. euphratica has a long growth cycle and a high growth rate, which can break wind, fix sand, green the environment, and protect farmland, making it an important afforestation tree species in arid and semiarid areas. The area of P. euphratica in Xinjiang accounts for 91.1% of its area in China. Studying the endophytic bacteria of P. euphratica can give people a systematic understanding of it and the adaptability of the endogenous flora to the host and special environments. In this study, by analyzing the endophytic bacteria of P. euphratica in different saline-alkali regions of Xinjiang, it was found that the bacteria in different tissues of P. euphratica changed with the change of soil salinity. Especially in the sap tissue of P. euphratica under extremely high salinity, the diversity of endogenous bacteria was significantly lower than that in other tissues. These differential bacteria under different salinities were mostly related to the stress resistance of themselves and the host. Not only that, we also selected a strain of Bacillus with high stress resistance from the tissues of P. euphratica, which can survive under the extreme conditions of 10% NaCl and pH 11. We obtained a genome completion map of this strain, named it Bacillus haynesii P19 (GenBank accession no. PRJNA648288), and tried to use it for fermentation but in a different work, so as to develop it into a promising industrial fermentation chassis bacterium. Therefore, this study was of great significance for the understanding of endophytic bacteria in P. euphratica and the acquisition of extremophilic microbial resources.


Assuntos
Populus , Álcalis/metabolismo , Bactérias/genética , Endófitos/genética , Humanos , Populus/genética , Populus/metabolismo , Salinidade , Areia , Solo/química
20.
Biochem Biophys Res Commun ; 410(4): 714-20, 2011 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-21651897

RESUMO

During Drosophila optic lobe development, proliferation and differentiation must be tightly modulated to reach its normal size for proper functioning. The JAK/STAT pathway plays pleiotropic roles in Drosophila development and in the larval brain, has been shown to inhibit medulla neuroblast formation. In this study, we find that JAK/STAT activity is required for the maintenance and proliferation of the neuroepithelial stem cells in the optic lobe. In loss-of-function JAK/STAT mutant brains, the neuroepithelial cells lose epithelial cell characters and differentiate prematurely while ectopic activation of this pathway is sufficient to induce neuroepithelial overgrowth in the optic lobe. We further show that Notch signaling acts downstream of JAK/STAT to control the maintenance and growth of the optic lobe neuroepithelium. Thus, in addition to its role in suppression of neuroblast formation, the JAK/STAT pathway is necessary and sufficient for optic lobe neuroepithelial growth.


Assuntos
Proteínas de Drosophila/fisiologia , Drosophila melanogaster/crescimento & desenvolvimento , Janus Quinases/fisiologia , Células-Tronco Neurais/fisiologia , Células Neuroepiteliais/fisiologia , Lobo Óptico de Animais não Mamíferos/crescimento & desenvolvimento , Fatores de Transcrição STAT/fisiologia , Fatores de Transcrição/fisiologia , Animais , Proliferação de Células , Proteínas de Drosophila/genética , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Feminino , Janus Quinases/genética , Células-Tronco Neurais/metabolismo , Células Neuroepiteliais/metabolismo , Lobo Óptico de Animais não Mamíferos/citologia , Lobo Óptico de Animais não Mamíferos/metabolismo , Receptores Notch/fisiologia , Fatores de Transcrição STAT/genética , Transdução de Sinais , Fatores de Transcrição/genética
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