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1.
Proc Natl Acad Sci U S A ; 121(17): e2319625121, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38640343

RESUMO

Distributed nonconvex optimization underpins key functionalities of numerous distributed systems, ranging from power systems, smart buildings, cooperative robots, vehicle networks to sensor networks. Recently, it has also merged as a promising solution to handle the enormous growth in data and model sizes in deep learning. A fundamental problem in distributed nonconvex optimization is avoiding convergence to saddle points, which significantly degrade optimization accuracy. We find that the process of quantization, which is necessary for all digital communications, can be exploited to enable saddle-point avoidance. More specifically, we propose a stochastic quantization scheme and prove that it can effectively escape saddle points and ensure convergence to a second-order stationary point in distributed nonconvex optimization. With an easily adjustable quantization granularity, the approach allows a user to control the number of bits sent per iteration and, hence, to aggressively reduce the communication overhead. Numerical experimental results using distributed optimization and learning problems on benchmark datasets confirm the effectiveness of the approach.

2.
FASEB J ; 38(11): e23731, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38855909

RESUMO

Ca2+ permeation through TRPV4 in fibroblasts is associated with pathological matrix degradation. In human gingival fibroblasts, IL-1ß binding to its signaling receptor (IL-1R1) induces activation of extracellular regulated kinase (ERK) and MMP1 expression, processes that require Ca2+ flux across the plasma membrane. It is not known how IL-1R1, which does not conduct Ca2+, generates Ca2+ signals in response to IL-1. We examined whether TRPV4 mediates the Ca2+ fluxes required for ERK signaling in IL-1 stimulated gingival fibroblasts. TRPV4 was immunostained in fibroblasts of human gingival connective tissue and in focal adhesions of cultured mouse gingival fibroblasts. Human gingival fibroblasts treated with IL-1ß showed no change of TRPV4 expression but there was increased MMP1 expression. In mouse, gingival fibroblasts expressing TRPV4, IL-1 strongly increased [Ca2+]i. Pre-incubation of cells with IL-1 Receptor Antagonist blocked Ca2+ entry induced by IL-1 or the TRPV4 agonist GSK101. Knockout of TRPV4 or expression of a non-Ca2+-conducting TRPV4 pore-mutant or pre-incubation with the TRPV4 inhibitor RN1734, blocked IL-1-induced Ca2+ transients and expression of the mouse interstitial collagenase, MMP13. Treatment of mouse gingival fibroblasts with GSK101 phenocopied Ca2+ and ERK responses induced by IL-1; these responses were absent in TRPV4-null cells or cells expressing a non-conducting TRPV4 pore-mutant. Immunostained IL-1R1 localized with TRPV4 in adhesions within cell extensions. While TRPV4 immunoprecipitates analyzed by mass spectrometry showed no association with IL-1R1, TRPV4 associated with Src-related proteins and Src co-immunoprecipitated with TRPV4. Src inhibition reduced IL-1-induced Ca2+ responses. The functional linkage of TRPV4 with IL-1R1 expands its repertoire of innate immune signaling processes by mediating IL-1-driven Ca2+ responses that drive matrix remodeling in fibroblasts. Thus, inhibiting TRPV4 activity may provide a new pharmacological approach for blunting matrix degradation in inflammatory diseases.


Assuntos
Sinalização do Cálcio , Fibroblastos , Gengiva , Canais de Cátion TRPV , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/genética , Animais , Humanos , Camundongos , Fibroblastos/metabolismo , Gengiva/metabolismo , Gengiva/citologia , Cálcio/metabolismo , Sistema de Sinalização das MAP Quinases , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Interleucina-1/metabolismo , Interleucina-1/farmacologia , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 1 da Matriz/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacologia
3.
BMC Plant Biol ; 24(1): 182, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475753

RESUMO

BACKGROUND: Cotton boll shedding is one of the main factors adversely affecting the cotton yield. During the cotton plant growth period, low light conditions can cause cotton bolls to fall off prematurely. In this study, we clarified the regulatory effects of low light intensity on cotton boll abscission by comprehensively analyzing the transcriptome and metabolome. RESULTS: When the fruiting branch leaves were shaded after pollination, all of the cotton bolls fell off within 5 days. Additionally, H2O2 accumulated during the formation of the abscission zone. Moreover, 10,172 differentially expressed genes (DEGs) and 81 differentially accumulated metabolites (DAMs) were identified. A KEGG pathway enrichment analysis revealed that the identified DEGs and DAMs were associated with plant hormone signal transduction and flavonoid biosynthesis pathways. The results of the transcriptome analysis suggested that the expression of ethylene (ETH) and abscisic acid (ABA) signaling-related genes was induced, which was in contrast to the decrease in the expression of most of the IAA signaling-related genes. A combined transcriptomics and metabolomics analysis revealed that flavonoids may help regulate plant organ abscission. A weighted gene co-expression network analysis detected two gene modules significantly related to abscission. The genes in these modules were mainly related to exosome, flavonoid biosynthesis, ubiquitin-mediated proteolysis, plant hormone signal transduction, photosynthesis, and cytoskeleton proteins. Furthermore, TIP1;1, UGT71C4, KMD3, TRFL6, REV, and FRA1 were identified as the hub genes in these two modules. CONCLUSIONS: In this study, we elucidated the mechanisms underlying cotton boll abscission induced by shading on the basis of comprehensive transcriptomics and metabolomics analyses of the boll abscission process. The study findings have clarified the molecular basis of cotton boll abscission under low light intensity, and suggested that H2O2, phytohormone, and flavonoid have the potential to affect the shedding process of cotton bolls under low light stress.


Assuntos
Reguladores de Crescimento de Plantas , Transcriptoma , Gossypium/genética , Peróxido de Hidrogênio/metabolismo , Perfilação da Expressão Gênica/métodos , Metaboloma , Flavonoides/metabolismo , Regulação da Expressão Gênica de Plantas
4.
IUBMB Life ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822621

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs that can actively participate in post-transcriptional regulation of genes. A number of studies have shown that miRNAs can serve as important regulators of cancer cell growth, differentiation, and apoptosis. They can also act as markers for the diagnosis and prognosis of certain cancers. To explore the potential prognosis-related miRNAs in liver cancer patients, to provide theoretical basis for early diagnosis and prognosis of liver cancer, as well as to provide a new direction for the targeted therapy of liver cancer. The miRNA expression profiles of liver cancer patients in the the Cancer Genome Atlas database were comprehensively analyzed and various prognostic-related miRNAs of liver cancer were screened out. The data was further subjected to survival analysis, prognostic analysis, gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis, microenvironment analysis, and drug sensitivity analysis by R Language version 4.2.0. Finally, the screened miRNAs were further validated by different experiments. Thus, miNRAs involved in liver cancer diagnosis and prognosis were identified. MiRNA-3680-3p was found to be significantly different in 10 different cancers, including liver cancer, and was significantly associated with the microenvironment, survival, and prognosis of liver cancer patients. In addition, drug sensitivity analysis revealed that miRNA-3680-3p can provide a useful reference for drug selection in targeted therapy for liver cancer. MiRNA-3680-3p can serve as a biomarker for the diagnosis and prognosis of liver cancer patients and down-regulation of miRNA-3680-3p could significantly inhibit both the proliferation and migration of liver cancer cells.

5.
Opt Express ; 32(10): 17942-17952, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858962

RESUMO

The interaction between the intrinsic polarity of the host material and the TADF guest material affects charge injection and transport, exciton formation, charge recombination, and emission mechanisms. Therefore, understanding and controlling the interaction between the intrinsic polarity of the host material and the TADF guest material is very important to realize efficient TADF-OLED devices. This study investigated the molecular interaction between different polar host materials and a thermally activated delayed fluorescence material (DMAc-PPM). It has been found that interaction between the host and guest (π-π stacking interaction, multiple CH/π contacts) greatly influence the molecular transition dipole moment orientation of the guest. And the OLED devices based on the strong polar host (DPEPO) exhibited the highest EQEmax and lowest luminescence intensity, while devices using the weaker polar hosts mCP and CBP achieved higher luminance and lower EQEmax. Then, the strong polar host DPEPO was mixed with the weaker polar hosts CBP and mCP, respectively. The devices prepared based on the mixed-host DPEPO: mCP showed a 2.2 times improvement in EQEmax from 6.3% to 20.1% compared to the single-host mCP. The devices prepared based on the mixed-host DPEPO: CBP showed a 3.1 times improvement in luminance intensity from 1023 cd/m2 to 4236 cd/m2 compared to the single host of DPEPO. This suggests that optimizing the polarity of host materials has the potential to enhance the performance of solution prepared OLED devices.

6.
Microb Pathog ; 190: 106628, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38508422

RESUMO

Rotavirus infections in suckling and weaning piglets cause severe dehydration and death, resulting in significant economic losses in the pig breeding industry. With the continuous emergence of porcine rotavirus (PoRV) variants and poor vaccine cross-protection among various genotypes, there is an urgent need to develop alternative strategies such as seeking effective antiviral products from nature, microbial metabolites and virus-host protein interaction. Sialidases play a crucial role in various physiopathological processes and offer a promising target for developing antivirus drugs. However, the effect of bacterial-derived sialidases on the infection of PoRVs remains largely unknown. Herein, we investigated the impact of bacterial-derived sialidases (sialidase Cp and Vc) on PoRV strain OSU(Group A) infection, using differentiated epithelial monkey kidney cells (MA104) as a model. Our results indicated that the pretreatment of MA104 with exogenous sialidases effectively suppressed PoRV OSU in a concentration-dependent manner. Notably, even at a concentration of 0.01 µU/mL, sialidases significantly inhibited the virus (MOI = 0.01). Meanwhile, we found that sialidase Vc pretreatment sharply reduced the binding rate of PoRV OSU. Last, we demonstrated that PoRV OSU might recognize α-2,3-linked sialic acid as the primary attachment factor in MA104. Our findings provide new insights into the underlying mechanism of PoRV OSU infections, shedding lights on the development of alternative antivirus approaches based on bacteria-virus interaction.


Assuntos
Neuraminidase , Infecções por Rotavirus , Rotavirus , Replicação Viral , Animais , Neuraminidase/metabolismo , Neuraminidase/genética , Rotavirus/efeitos dos fármacos , Rotavirus/fisiologia , Suínos , Replicação Viral/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/virologia , Células Epiteliais/microbiologia , Ligação Viral/efeitos dos fármacos , Ácido N-Acetilneuramínico/metabolismo , Ácido N-Acetilneuramínico/farmacologia , Antivirais/farmacologia , Haplorrinos , Doenças dos Suínos/virologia , Doenças dos Suínos/microbiologia
7.
Neurochem Res ; 49(5): 1268-1277, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38337134

RESUMO

Electroacupuncture (EA) effectively improves arthritis-induced hyperalgesia and allodynia by repressing spinal microglial activation, which plays a crucial role in pain hypersensitivity following tissue inflammation. However, the mechanism by which EA suppresses spinal microglial activation in monoarthritis (MA) remains unclear. In the present study, a rat model of MA was established through unilateral ankle intra-articular injection of complete Freund's adjuvant (CFA). The relationship among P2Y12 receptor (P2Y12R) expression, spinal microglial activation, and EA analgesia was investigated using quantitative real-time PCR (qRT‒PCR), western blotting, immunofluorescence (IF), and behavioral testing. The results found that EA treatment at the ipsilateral "Huantiao" (GB30) and "Yanglingquan" (GB34) acupoints markedly attenuated pain and spinal microglia M1 polarization in MA rats. In particular, P2Y12R expression was significantly increased at the mRNA and protein levels in the spinal dorsal horn in MA rats, whereas EA treatment effectively repressed the MA-induced upregulation of P2Y12R. IF analysis further revealed that most P2Y12R was expressed in microglia in the spinal dorsal horn. Pharmacological inhibition of P2Y12R by its antagonist (AR-C69931MX) decreased MA-induced spinal microglial activation and subsequent proinflammatory cytokine production. Consequently, AR-C69931MX significantly intensified the anti-pain hypersensitive function of EA in MA rats. Taken together, these results demonstrate that EA alleviates MA-induced pain by suppressing P2Y12R-dependent microglial activation.


Assuntos
Artrite , Eletroacupuntura , Ratos , Animais , Microglia/metabolismo , Ratos Sprague-Dawley , Eletroacupuntura/métodos , Medula Espinal/metabolismo , Dor/induzido quimicamente , Dor/metabolismo , Hiperalgesia/terapia , Hiperalgesia/tratamento farmacológico , Artrite/metabolismo , Artrite/terapia
8.
Langmuir ; 40(5): 2773-2780, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38275660

RESUMO

As an advanced water purification technology, magnetic nanoabsorbents are highly attractive for their sustainability, robustness, and energy efficiency. However, magnetic responsiveness and high adsorptive capacity are irreconcilable during the design and synthesis of a high-performance magnetic nanoabsorbent. Here, we address this issue by designing a kind of mesoporous magnetic polymer hybrid microspheres, where functional polymers such as polyrhodanine and polypyrrole were attached to the pore walls in the interior of mesoporous Fe3O4 microspheres through in situ polymerization. Due to the integrated large saturation magnetic moment, porous structure, and dense polymer layer, the mesoporous magnetic polymer hybrid microspheres demonstrated fast magnetic responsiveness, excellent recycling performance, and high adsorption capacities toward Pb(II) ions (189 mg g-1) for polyrhodanine and Cr(VI) ions (199 mg g-1) for polypyrrole. Furthermore, their potential application in wastewater treatment was verified by a self-made magnetic separation column, where the designed magnetic nanoabsorbent exhibits significant advantages including rapid separation of heavy metal ions and high outflow. This study provided a promising magnetic polymer hybrid nanoabsorbent for realizing efficient removal of heavy metal ions from wastewater.

9.
Eur Spine J ; 33(8): 3275-3283, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38858266

RESUMO

BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) caused by osteoporosis is a common clinical fracture type. There are many surgical treatment options for OVCF, but there is a lack of comparison among different options. Therefore, we counted a total of 104 cases of OVCF operations with different surgical plans, followed up the patients, and compared the surgical outcome indications before, after and during the follow-up. METHOD: 104 patients who underwent posterior osteotomy (Modified PSO, SPO, PSO, VCR) and kyphosis correction surgery at our hospital between April 2006 and August 2021 with a minimum follow-up period of 24 months were included. All cases were injuries induced by a fall incurred while standing or lifting heavy objects without high-energy trauma. The mean CT value was 71 HU, which was below 110 HU, indicating severe osteoporosis. The indications for surgery included gait disturbance due to severe pain with pseudarthrosis, increased kyphotic angle, and progressive neurological symptoms. Pre- and postoperative CL, TLK, TK, PrTK, TKmax, GK, LL, PI, SS, PT, SVA, TPA, were investigated radiologically. Additionally, We evaluated estimated blood loss, surgical time and perioperative symptom. RESULT: The results show, after operation, TLK (37.32 ± 10.61° vs. 11.01 ± 8.06°, P < 0.001), TK (35.42 ± 17.64° vs. 25.62 ± 12.24°, P < 0.001), TKmax (49.71 ± 16.32° vs. 24.12 ± 13.34°, P < 0.001), SVA (44.91 ± 48.67 vs. 23.52 ± 30.21, P = 0.013), CL (20.23 ± 13.21° vs. 11.45 ± 9.85°, P = 0.024) and TPA (27.44 ± 12.76° vs. 13.91 ± 9.24°, P = 0.009) were improved significantly in modified Pedicle subtraction osteotomy (mPSO) after operation. During follow-up, TLK (37.32 ± 10.61° vs. 13.88 ± 10.02°, P < 0.001) and TKmax (49.71 ± 16.32° vs. 24.12 ± 13.34°, P < 0.001) were improved significantly in Modified PSO group. In additon, estimated blood loss (790.0 ± 552.2 ml vs. 987.0 ± 638.5 ml, P = 0.038), time of operation (244.1 ± 63.0 min vs. 292.4 ± 87.6 min, P = 0.025) were favorable in Modified PSO group compared to control group. CONCLUSION: To conclude, mPSO could acquire a favorable degree of kyphosis correction as well as fewer follow-up complications. Compared with other surgical methods, it also has the advantages of less surgical trauma and shorter operation time. It can be an effective solution for the treatment of OVCF.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Osteotomia , Fraturas da Coluna Vertebral , Humanos , Fraturas por Compressão/cirurgia , Feminino , Masculino , Osteotomia/métodos , Idoso , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Resultado do Tratamento , Cifose/cirurgia , Cifose/etiologia
10.
Int J Mol Sci ; 25(5)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38474071

RESUMO

Mycoplasma gallisepticum is one of the smallest self-replicating organisms. It causes chronic respiratory disease, leading to significant economic losses in poultry industry. Following M. gallisepticum invasion, the pathogen can persist in the host owing to its immune evasion, resulting in long-term chronic infection. The strategies of immune evasion by mycoplasmas are very complex and recent research has unraveled these sophisticated mechanisms. The antigens of M. gallisepticum exhibit high-frequency changes in size and expression cycle, allowing them to evade the activation of the host humoral immune response. M. gallisepticum can invade non-phagocytic chicken cells and also regulate microRNAs to modulate cell proliferation, inflammation, and apoptosis in tracheal epithelial cells during the disease process. M. gallisepticum has been shown to transiently activate the inflammatory response and then inhibit it by suppressing key inflammatory mediators, avoiding being cleared. The regulation and activation of immune cells are important for host response against mycoplasma infection. However, M. gallisepticum has been shown to interfere with the functions of macrophages and lymphocytes, compromising their defense capabilities. In addition, the pathogen can cause immunological damage to organs by inducing an inflammatory response, cell apoptosis, and oxidative stress, leading to immunosuppression in the host. This review comprehensively summarizes these evasion tactics employed by M. gallisepticum, providing valuable insights into better prevention and control of mycoplasma infection.


Assuntos
Infecções por Mycoplasma , Mycoplasma gallisepticum , Doenças das Aves Domésticas , Animais , Evasão da Resposta Imune , Galinhas , Aves Domésticas
11.
Environ Sci Pollut Res Int ; 31(10): 14537-14552, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38308167

RESUMO

Constructed wetland substrates (CWSs) have received considerable attention owing to their importance in adsorbing and degrading pollutants, providing growth attachment points for microorganisms, and supporting wetland plants. There are differences in the configurations and functions of constructed wetlands (CWs) for treating different water bodies and sewage, resulting in a wide variety of substrates. Research on the application and mechanism of CWSs is not sufficiently systematic. Therefore, the current research advancements and hotspots must be identified. Hence, we used CiteSpace to analyze 1955 English publications from the core collection database of the Web of Science to assess the current state of the CWS research field. Based on the cooperative network analysis, the roles of various countries, institutions, and authors in research on CWSs were reviewed. Keyword co-occurrence and cluster analyses were used to discuss the transformation of CWSs from removing traditional pollutants to emerging pollutants and the transition from incorporating natural substrates to artificial substrates. Finally, we underscored the need for more emphasis to be placed on the collocation and application of the CWSs at different latitudes. Furthermore, the substrate micro-interface process and its effects on the interaction patterns of pollutants and microorganisms should be thoroughly investigated to provide theoretical guidance for the development of wetland applications and mechanisms.


Assuntos
Poluentes Ambientais , Áreas Alagadas , Humanos , Análise por Conglomerados , Bases de Dados Factuais , Esgotos
12.
Nat Commun ; 15(1): 2415, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499520

RESUMO

Phenols and anilines are of extreme importance for medicinal chemistry and material science. The development of efficient approaches to prepare both compounds has thus long been a vital research topic. The utility of phenols and anilines directly reflects the identity and pattern of substituents on the benzenoid ring. Electrophilic substitutions remain among the most powerful synthetic methods to substituted phenols and anilines, yet in principle achieving ortho- and para-substituted products. Therefore, the selective preparation of meta-substituted phenols and anilines is the most significant challenge. We herein report an efficient copper-catalyzed dehydrogenation strategy to exclusively synthesize meta-carbonyl phenols and anilines from carbonyl substituted cyclohexanes. Mechanistic studies indicate that this transformation undergoes a copper-catalyzed dehydrogenation/allylic hydroxylation or amination/oxidative dehydrogenation/aromatization cascade process.

13.
Sci Rep ; 14(1): 4565, 2024 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-38403645

RESUMO

The benign and malignant status of solitary pulmonary nodules (SPNs) is a key determinant of treatment decisions. The main objective of this study was to validate the efficacy of machine learning (ML) models featured with dual-layer detector spectral computed tomography (DLCT) parameters in identifying the benign and malignant status of SPNs. 250 patients with pathologically confirmed SPN were included in this study. 8 quantitative and 16 derived parameters were obtained based on the regions of interest of the lesions on the patients' DLCT chest enhancement images. 6 ML models were constructed from 10 parameters selected after combining the patients' clinical parameters, including gender, age, and smoking history. The logistic regression model showed the best diagnostic performance with an area under the receiver operating characteristic curve (AUC) of 0.812, accuracy of 0.813, sensitivity of 0.750 and specificity of 0.791 on the test set. The results suggest that the ML models based on DLCT parameters are superior to the traditional CT parameter models in identifying the benign and malignant nature of SPNs, and have greater potential for application.


Assuntos
Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Humanos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Diagnóstico Diferencial , Tomografia Computadorizada por Raios X/métodos , Curva ROC , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia
14.
Org Lett ; 26(1): 41-45, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38149590

RESUMO

The development of an efficient method for the synthesis of C4 oxy-substituted indoles is an appealing yet challenging task. Herein, we report a general palladium-catalyzed TDG approach for the direct C4-H acyloxylation of indoles. The protocol features atom and step economy, excellent regioselectivity, and good tolerance of functional groups. Moreover, the reaction can accommodate a range of carboxylic acids including benzoic acids, phenylacetic acids, and aliphatic acids.

15.
Int J Biol Macromol ; 259(Pt 2): 129313, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38216012

RESUMO

Prolyl endopeptidases (PEP) from Sphingomonas capsulata (sc) and Myxococcus xanthus (mx) selectively degrade gluten peptides in vitro, offering a potential therapeutic strategy for celiac disease. However, the mechanisms governing the interaction of these enzymes with their substrates remain unclear. In this study, conventional molecular dynamics simulations with a microsecond timescale and targeted molecular dynamics simulations were performed to investigate the native states of mxPEP and scPEP enzymes, as well as their allosteric binding with a representative substrate, namely, Z-Ala-Pro-p-nitroanilide (pNA). The simulations reveal that the native scPEP is in an open state, while the native mxPEP is in a closed state. When pNA approaches a closed mxPEP, it binds to an allosteric pocket located at the first and second ß-sheet of the ß-propeller domain, inducing the opening of this enzyme. Neither enzyme is active in the open or partly-open states. Enzymatic activity is enabled only when the catalytic pocket in the closed state fully accommodates the substrates. The internal capacity of the catalytic pocket of PEP in the closed state determines the maximum size of the gluten peptides that the enzymes can catalyze. The present work provides essential molecular dynamics information for the redesign or engineering of PEP enzymes.


Assuntos
Doença Celíaca , Prolil Oligopeptidases , Humanos , Prolil Oligopeptidases/metabolismo , Serina Endopeptidases/química , Simulação de Dinâmica Molecular , Glutens/química , Peptídeos/química
16.
Plants (Basel) ; 13(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38475489

RESUMO

Cold shock proteins (CSPs) are DNA/RNA binding proteins with crucial regulatory roles in plant growth, development, and stress responses. In this study, we employed bioinformatics tools to identify and analyze the physicochemical properties, conserved domains, gene structure, phylogenetic relationships, cis-acting elements, subcellular localization, and expression patterns of the cotton CSP gene family. A total of 62 CSP proteins were identified across four cotton varieties (Gossypium arboreum, Gossypium raimondii, Gossypium barbadense, Gossypium hirsutum) and five plant varieties (Arabidopsis thaliana, Brassica chinensis, Camellia sinensis, Triticum aestivum, and Oryza sativa). Phylogenetic analysis categorized cotton CSP proteins into three evolutionary branches, revealing similar gene structures and motif distributions within each branch. Analysis of gene structural domains highlighted the conserved CSD and CCHC domains across all cotton CSP families. Subcellular localization predictions indicated predominant nuclear localization for CSPs. Examination of cis-elements in gene promoters revealed a variety of elements responsive to growth, development, light response, hormones, and abiotic stresses, suggesting the potential regulation of the cotton CSP family by different hormones and their involvement in diverse stress responses. RT-qPCR results suggested that GhCSP.A1, GhCSP.A2, GhCSP.A3, and GhCSP.A7 may play roles in cotton's response to low-temperature stress. In conclusion, our findings underscore the significant role of the CSP gene family in cotton's response to low-temperature stress, providing a foundational basis for further investigations into the functional aspects and molecular mechanisms of cotton's response to low temperatures.

17.
Cell Cycle ; 23(4): 353-368, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38547309

RESUMO

MiRNAs play crucial regulatory roles in the growth and development of tumor cells by serving as carriers of post-transcriptional regulatory information derived from genes. Investigating the potential function and clinical significance of miRNA-mediated mRNA regulatory networks in liver cancer can offer novel insights and therapeutic strategies for the treatment of this disease. We identified 300 differentially expressed miRNAs, and five miRNAs were identified to be correlated with overall survival and could be used as an independent prognostic. GO enrichment analysis mainly included carboxylic acid biosynthesis, organic acid biosynthesis, peroxisomal membrane, microsomal membrane, DNA binding, C-acyltransferase activity, etc. KEGG enrichment analysis showed that the pathways of target genes related to liver cancer were mainly focused on butyric acid metabolism and partial amino acid metabolism. Eight of the top 10 HUB genes were associated with prognosis, and the expression of four genes was positively correlated with prognosis, of which ABAT, BHMT, and SHMT1 were target genes of hsa-miR-5003-3p. MiR-5003-3p inhibits ABAT/BHMT/SHMT1 expression, thereby promoting liver cancer development. Overall, our study provides new ideas for the treatment of liver cancer, and these five miRNAs may be independent prognostic biomarkers and therapeutic targets for liver cancer patients. And miR-5003-3p may be a critical factor in the mechanism of liver cancer development.


Assuntos
Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Neoplasias Hepáticas , MicroRNAs , RNA Mensageiro , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Feminino , Masculino , Perfilação da Expressão Gênica
18.
J Vis Exp ; (207)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38884484

RESUMO

Pyroptosis is an inflammatory type of programmed cell death predominantly driven by the formation of plasma membrane pores by the N-terminus generated from the cleaved Gasdermin (GSDM) family proteins. Examination of membrane-attached GSDM-NT by Western Blot is the most commonly used method for evaluating pyroptosis. However, it is difficult to differentiate cells with pyroptosis from other forms of cell death using this method. In this study, Infectious Bursal Disease Virus (IBDV)-infected DF-1 cells were employed as a model to quantify the proportion of cells undergoing pyroptosis by flow cytometry, utilizing specific antibodies against the N-terminal fragment of chicken GSDME (chGSDME-NT) and propidium iodide (PI) staining. The chGSDME-NT-positive cells were readily detectable by flow cytometry using Alexa Fluor 647-labeled anti-chGSDME-NT antibodies. Moreover, the proportion of chGSDME-NT/PI double-positive cells in IBDV-infected cells (around 33%) was significantly greater than in mock-infected controls (P < 0.001). These findings indicate that examination of membrane-bound chGSDME-NT by flow cytometry is an effective approach for determining pyroptotic cells among cells undergoing cell death.


Assuntos
Galinhas , Citometria de Fluxo , Vírus da Doença Infecciosa da Bursa , Piroptose , Citometria de Fluxo/métodos , Animais , Vírus da Doença Infecciosa da Bursa/imunologia , Linhagem Celular
19.
Heliyon ; 10(15): e35857, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170416

RESUMO

The increasing emergence and spread of antibiotic resistance accelerate the desire for antibiotic alternatives. Plant extracts have emerged as a promising and relatively unexplored area of research as potential substitutes. Herein, we investigated the prevalence and distribution patterns of bacteria on egg surfaces and evaluated the inhibitory effects of mangosteen extract on these surface bacteria. In addition, we examined the antioxidant activity and egg quality in improving the ability of mangosteen extract. The results showed that the predominant bacteria isolated from eggshells were Gram-positive, with Staphylococcus and Micrococcus as the dominant genera. Notably, mangosteen extract exhibited significant bactericidal activity, effectively inhibiting Gram-positive bacteria on the surface of chicken eggshells. Moreover, the supplementation of mangosteen extract in the feed of laying hens yielded a noteworthy improvement in egg quality, accompanied by positively shaped structure and function of microbial communities on the egg surface and in the feces. Collectively, our findings suggested that mangosteen extract was an effective alternative to traditional antibiotics, offering valuable insights for animal husbandry development.

20.
Bioresour Technol ; : 131295, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39155017

RESUMO

The cultivation of microalgae is significantly influenced by light intensity and utilization efficiency. This study developed a modified Cornet (M-Cornet) model to assess the distribution of light intensity and flux in microalgae cultivation systems. Algal biofilm cultivation represents a more concentrated approach of algal suspension cultivation. Both follow the M-Cornet model and exhibit the same growth rates when cultured under identical conditions. Algal pigments and morphologies greatly impact the light absorption and scattering, resulting in light attenuation in intensity, penetration distance and light flux distribution. Algae varieties exhibit diverse light flux characteristics. 37% - 90% of the incident light is absorbed, of which, 80% to 90% is dissipated as heat. 10% to 63% of the incident light is scattered off the photobioreactor. The overall light utilization efficiency ranges 6% to 13%. The light footprint using the M-Cornet model offers valuable insights for photobioreactors designing and cultivation operating.

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