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As a critical step during innate response, the cytoplasmic ß subunit (IFN-γR2) of interferon-γ receptor (IFN-γR) is induced and translocates to plasma membrane to join α subunit to form functional IFN-γR to mediate IFN-γ signaling. However, the mechanism driving membrane translocation and its significance remain largely unknown. We found, unexpectedly, that mice deficient in E-selectin, an endothelial cell-specific adhesion molecule, displayed impaired innate activation of macrophages upon Listeria monocytogenes infection yet had increased circulating IFN-γ. Inflammatory macrophages from E-selectin-deficient mice had less surface IFN-γR2 and impaired IFN-γ signaling. BTK elicited by extrinsic E-selectin engagement phosphorylates cytoplasmic IFN-γR2, facilitating EFhd2 binding and promoting IFN-γR2 trafficking from Golgi to cell membrane. Our findings demonstrate that membrane translocation of cytoplasmic IFN-γR2 is required to activate macrophage innate response against intracellular bacterial infection, identifying the assembly of functional cytokine receptors on cell membrane as an important layer in innate activation and cytokine signaling.
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Selectina E/metabolismo , Imunidade Inata , Receptores de Interferon/metabolismo , Animais , Proteínas de Ligação ao Cálcio/antagonistas & inibidores , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Membrana Celular/metabolismo , Selectina E/deficiência , Selectina E/genética , Complexo de Golgi/metabolismo , Interferon gama/sangue , Interferon gama/metabolismo , Listeria/patogenicidade , Ativação de Macrófagos , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Transporte Proteico , Células RAW 264.7 , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores de Interferon/deficiência , Receptores de Interferon/genética , Transdução de Sinais , Receptor de Interferon gamaRESUMO
In a gene chip analysis, rice (Oryza sativa) OsSMP2 gene expression was induced under various abiotic stresses, prompting an investigation into its role in drought resistance and abscisic acid signaling. Subsequent experiments, including qRT-PCR and ß-glucuronidase activity detection, affirmed the OsSMP2 gene's predominant induction by drought stress. Subcellular localization experiments indicated the OsSMP2 protein primarily localizes to the cell membrane system. Overexpressing OsSMP2 increased sensitivity to exogenous abscisic acid, reducing drought resistance and leading to reactive oxygen species accumulation under drought stress. Conversely, in simulated drought experiments, OsSMP2-silenced transgenic plants showed significantly longer roots compared with the wild-type Nipponbare. These results suggest that OsSMP2 overexpression negatively affects rice drought resistance, offering valuable insights into molecular mechanisms, and highlight OsSMP2 as a potential target for enhancing crop resilience to drought stress.
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Ácido Abscísico , Secas , Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Estresse Fisiológico , Oryza/genética , Oryza/fisiologia , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Ácido Abscísico/metabolismo , Plantas Geneticamente Modificadas , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genéticaRESUMO
Inspired by the advanced integrated sensing and communication (ISAC), in this Letter, we explore the non-line-of-sight (NLoS) optical channels formed by reflections from the ground or objects to establish an integrated channel model for simultaneous communication and sensing. The integrated channel model can, on the one hand, perceive the changes in the surrounding environment and, on the other hand, determine whether these changes positively or negatively affect the quality of communication simultaneously. To validate the effectiveness of the proposed model, from sensing, we analyze the impact of various floor materials and visible light communication (VLC) users on the integrated channel; from communication, we characterize the influence of perceived environmental changes on communication performance by calculating throughput. Experimental results confirm the capability of the derived model, which can support the design and deployment of VL-based ISAC networks.
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OBJECTIVE: This article describes a novel 3D-printed template armed with interproximal matrices to isolate interproximal contact areas and guide injectable resin composite for consecutive closure of multiple diastema. CLINICAL CONSIDERATIONS: Among several treatment options proposed for diastema closure, direct resin composite is noninvasive and easy to repair. The "composite injection technique" has been introduced to improve time efficiency and reduce technique sensitivity for clinicians. However, in the case of multiple diastema, the overflow of excess resin materials onto the adjacent teeth during injection poses challenges for recontouring the interproximal anatomy. A 3D-printed template with special-designed gaps at interproximal areas was designed and fabricated based on a virtual diagnostic wax-up. Flowable resin composite was then consecutively injected through the template to close diastemata at multiple adjacent teeth. CONCLUSION: This technique using a 3D-printed template with interproximal isolation design contributed to an efficient and accurate operation for multiple anterior diastema closure. CLINICAL SIGNIFICANCE: Efficient and accurate freehand buildups of composite restoration for multiple diastema are challenging in operative dentistry. The described noninvasive full digital workflow provides a predictable method to accurately recontour the multiple target restorations and reduce the chair-side time and technical sensitivity.
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This clinical report describes a digital workflow for the rehabilitation of an 8-year-old patient diagnosed with ectodermal dysplasia. Based on the patient's digital primary casts, small custom trays and an arch tracer were designed and 3-dimensionally printed. The mandibular custom tray and retention plate with a tracing screw were assembled with tracing plate, forming an individual assembled mini-arch tracer system to record the jaw relationship together with a conventional facebow and a digital articulator. In addition, composite resin injection guides were designed and fabricated to form the predesigned targeted shape of the abutment teeth and provide a buffer. By following this workflow, complete overdentures with good fit, occlusion, and acceptable esthetics were delivered.
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Flavonoids are important secondary metabolites found in Juglans mandshurica Maxim., which is a precious reservoir of bioactive substances in China. To explore the antitumor actions of flavonoids (JMFs) from the waste branches of J. mandshurica, the following optimized purification parameters of JMFs by macroporous resins were first obtained. The loading concentration, flow rate, and loading volume of raw flavonoid extracts were 1.4 mg/mL, 2.4 BV/h, and 5 BV, respectively, and for desorption, 60% ethanol (4 BV) was selected to elute JMFs-loaded AB-8 resin at a flow rate of 2.4 BV/h. This adsorption behavior can be explained by the pseudo-second-order kinetic model and Langmuir isotherm model. Subsequently, JMFs were identified using Fourier transform infrared combined with high-performance liquid chromatography and tandem mass spectrometry, and a total of 156 flavonoids were identified. Furthermore, the inhibitory potential of JMFs on the proliferation, migration, and invasion of HepG2 cells was demonstrated. The results also show that exposure to JMFs induced apoptotic cell death, which might be associated with extrinsic and intrinsic pathways. Additionally, flow cytometry detection found that JMFs exposure triggered S phase arrest and the generation of reactive oxygen species in HepG2 cells. These findings suggest that the JMFs purified in this study represent great potential for the treatment of liver cancer.
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Apoptose , Proliferação de Células , Flavonoides , Juglans , Juglans/química , Humanos , Flavonoides/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Apoptose/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Movimento Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Antineoplásicos/farmacologia , Antineoplásicos/químicaRESUMO
OBJECTIVE: To provide synthesized evidence on the association between sarcopenia and risk of mortality, recurrence and postoperative complications in patients with bladder cancer and undergoing radical cystectomy (RC). METHODS: Only studies with observational design that investigated the association between sarcopenia and outcomes of interest among patients with bladder cancer undergoing RC were included. The outcomes of interest were mortality, recurrence, and postoperative complications. The systematic search was conducted using three large databases, that is, PubMed, EMBASE, and Scopus. A random effects model was used for the analysis and pooled effect sizes were reported as odds ratio (OR) or hazards ratio (HR) along with 95% confidence intervals (CIs). RESULTS: A total of 21 studies with 4997 patients were included. Compared to non-sarcopenic subjects, those with sarcopenia had increased risk of all-cause mortality (HR 1.45, 95% CI: 1.32, 1.61), cancer-specific mortality (HR 1.74, 95% CI: 1.49, 2.03) and a lower recurrence free survival (HR 1.84, 95% CI: 1.30, 2.62). Patients with sarcopenia also had higher risk of developing complications within 90 days postoperatively (OR 1.77, 95% CI: 1.23, 2.55). CONCLUSION: Sarcopenia among patients with bladder cancer and managed using RC is associated with adverse survival outcomes and an increased risk of postoperative complications.
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Cistectomia , Complicações Pós-Operatórias , Sarcopenia , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/mortalidade , Cistectomia/métodos , Cistectomia/efeitos adversos , Sarcopenia/complicações , Sarcopenia/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Masculino , Feminino , Resultado do Tratamento , Idoso , Fatores de Risco , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Large cross-arch free-end surgical guides can obscure the visual field, compromising surgical accuracy due to insufficient stability at the free-end. This in vitro study aims to evaluate the accuracy of novel digital non-cross-arch surgical guides designed for implant placement at the mandibular free-end, incorporating tooth undercut retention and screw-bone support. MATERIALS AND METHODS: A mandibular dental model lacking left molars was utilized to fabricate unilateral (cross-arch) tooth-supported surgical guides (GT I, n = 20). Subsequently, two additional types of surgical guides were fabricated: GT II (covering two teeth, n = 20) and GT III (covering three teeth, n = 20). These novel surgical guides were designed to utilize the undercut of the supporting teeth for retention and enhance stability with screw-bone support at the guide's free-end. Furthermore, 60 identical guiding blocks were assembled on the three types of surgical guides to facilitate the implants' insertion. On a phantom head, 120 implant replicas were placed at the Federal Dentaire Internationale (FDI) teeth positions #36 and #37 on the dental model, employing a combination of surgical guides and guiding blocks. To assess accuracy, planned and placed implant positions were compared using intraoral optical scanning. Discrepancies in angulation and linear deviations, including the coronal/apical 3D deviations, lateral deviation as well as depth deviation, were measured. Statistical analysis was performed using two-way ANOVA and Bonferroni test (α = 0.05). RESULTS: GT I exhibited significantly largest discrepancies, including angular and linear deviations at the crest and apex at every implant site. Especially in depth, at implant site #36, the mean deviation value of GT I (0.27 ± 0.13 mm) was twice as large as GT III (0.13 ± 0.07 mm), and almost twice as large as GT II (0.14 ± 0.08 mm). However, at implant site #37, this deviation increased to almost a five-fold relationship between GT I (0.63 ± 0.12 mm) and II (0.14 ± 0.09 mm), as well as between GT I and III (0.13 ± 0.09 mm). No significant discrepancies existed between the novel surgical guides at either implant site #36 or #37. CONCLUSION: This study provides a practical protocol for enhancing accuracy of implant placement and reducing the size of free-end surgical guides used at mandibular molar sites.
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Parafusos Ósseos , Mandíbula , Modelos Dentários , Cirurgia Assistida por Computador , Humanos , Mandíbula/cirurgia , Cirurgia Assistida por Computador/métodos , Implantação Dentária Endóssea/métodos , Desenho Assistido por Computador , Técnicas In VitroRESUMO
Thyroid cancer is the most common primary endocrine malignancy with papillary thyroid carcinoma (PTC) its most common subtype. The jump in diagnoses over last many years has prompted re-assessment of molecularly targeted therapies and the discovery of novel targets. Long non-coding RNAs (lncRNAs) are increasingly being assessed for their expression in various PTC models. Interestingly, in addition to cell line models, a large proportion of the reported studies have evaluated lncRNA levels in PTC patient samples providing an immediate clinical relevance of their findings. While most lncRNAs either promote or suppress PTC pathogenesis, data on individual lncRNAs is not very clear. As expected, lncRNAs function in PTC through sponging of microRNAs as well as modulation of several signaling pathways. The process of epithelial-mesenchymal transition and the PI3K/Akt and wnt signaling pathways have emerged as the primary targets of lncRNAs in PTC. This comprehensive review discusses all the information that is available on lncRNAs in PTC, ranging from in vitro and in vivo findings to the possible role of lncRNAs as diagnostic and/or prognostic biomarkers.
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MicroRNAs , RNA Longo não Codificante , Neoplasias da Glândula Tireoide , Linhagem Celular Tumoral , Proliferação de Células/genética , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , RNA Longo não Codificante/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologiaRESUMO
As a master nitrogen regulator in most actinomycetes, GlnR both governs central nitrogen metabolism and regulates many carbon, phosphate, and secondary metabolic pathways. To date, most studies have been focused on the GlnR regulon, while little is known about the transcriptional regulator for glnR itself. It has been observed that glnR transcription can be upregulated in Mycobacterium smegmatis under nitrogen-limited growth conditions; however, the detailed regulatory mechanism is still unclear. Here, we demonstrate that the glnR gene in M. smegmatis is transcriptionally activated by its product GlnR in response to nitrogen limitation. The precise GlnR binding site was successfully characterized in its promoter region using the electrophoretic mobility shift assay and the DNase I footprinting assay. Site mutagenesis and genetic analyses confirmed that the binding site was essential for in vivo self-activation of glnR transcription. Moreover, based on bioinformatic analyses, we discovered that most of the mycobacterial glnR promoter regions (144 out of 147) contain potential GlnR binding sites, and we subsequently proved that the purified M. smegmatis GlnR protein could specifically bind 16 promoter regions that represent 119 mycobacterial species, including Mycobacterium tuberculosis. Together, our findings not only elucidate the transcriptional self-regulation mechanism of glnR transcription in M. smegmatis but also indicate the ubiquity of the mechanism in other mycobacterial species. IMPORTANCE In actinomycetes, the nitrogen metabolism not only is essential for the construction of life macromolecules but also affects the biosynthesis of secondary metabolites and even virulence (e.g., Mycobacterium tuberculosis). The transcriptional regulation of genes involved in nitrogen metabolism has been thoroughly studied and involves the master nitrogen regulator GlnR. However, the transcriptional regulation of glnR itself remains elusive. Here, we demonstrated that GlnR functions as a transcriptional self-activator in response to nitrogen starvation in the fast-growing model Mycobacterium species Mycobacterium smegmatis. We further showed that this self-regulation mechanism could be widespread in other mycobacteria, which might be beneficial for those slow-growing mycobacteria to adapt to the nitrogen-starvation environments such as within human macrophages for M. tuberculosis.
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Mycobacterium tuberculosis , Autocontrole , Humanos , Nitrogênio/metabolismo , Regulação Bacteriana da Expressão Gênica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Mycobacterium smegmatis/metabolismo , Mycobacterium tuberculosis/metabolismo , Proteínas de Bactérias/metabolismoRESUMO
This study reports the successful development of a sustainable synthesis protocol for a phase-pure metal azolate framework (MAF-6) and its application in enzyme immobilization. An esterase@MAF-6 biocomposite was synthesized, and its catalytic performance was compared with that of esterase@ZIF-8 and esterase@ZIF-90 in transesterification reactions. Esterase@MAF-6, with its large pore aperture, showed superior enzymatic performance compared to esterase@ZIF-8 and esterase@ZIF-90 in catalyzing transesterification reactions using both n-propanol and benzyl alcohol as reactants. The hydrophobic nature of the MAF-6 platform was shown to activate the immobilized esterase into its open-lid conformation, which exhibited a 1.5- and 4-times enzymatic activity as compared to free esterase in catalyzing transesterification reaction using n-propanol and benzyl alcohol, respectively. The present work offers insights into the potential of MAF-6 as a promising matrix for enzyme immobilization and highlights the need to explore MOF matrices with expanded pore apertures to broaden their practical applications in biocatalysis.
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1-Propanol , Carboxilesterase , Esterases , Álcool BenzílicoRESUMO
Surface proteins of cells are generally recognized through receptor-ligand interactions (RLIs) in disease diagnosis, but their nonuniform spatial distribution and higher-order structure lead to low binding affinity. Constructing nanotopologies that match the spatial distribution of membrane proteins to improve the binding affinity remains a challenge. Inspired by the multiantigen recognition of immune synapses, we developed modular DNA-origami-based nanoarrays with multivalent aptamers. By adjusting the valency and interspacing of the aptamers, we constructed specific nanotopology to match the spatial distribution of target protein clusters and avoid potential steric hindrance. We found that the nanoarrays significantly enhanced the binding affinity of target cells and synergistically recognized low-affinity antigen-specific cells. In addition, DNA nanoarrays used for the clinical detection of circulating tumor cells successfully verified their precise recognition ability and high-affinity RLIs. Such nanoarrays will further promote the potential application of DNA materials in clinical detection and even cell membrane engineering.
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DNA , Oligonucleotídeos , DNA/química , Ligantes , Proteínas de Membrana , Membrana Celular/metabolismoRESUMO
BACKGROUND AND PURPOSE: To explore the association of systemic inflammatory index (SIRI), systemic immune-inflammatory index (SII) and inflammatory prognosis index (IPI) with 90d outcomes in patients with acute ischemic stroke (AIS) after intravenous thrombolysis. METHODS: The patients who underwent intravenous thrombolysis were enrolled in the present study from September 2019 to December 2022. According to the relevant blood indexes obtained in 24 h after admission, the corresponding values of SIRI, SII and IPI were calculated. The correlation among SIRI, SII, IPI, and admission NIHSS scores was examined by Spearman correlation analysis. ROC curve analysis was conducted to determine the optimal cut-off value of SIRI, SII, IPI, and their corresponding sensitivity and specificity to evaluate their predictive value on admission for poor prognosis. To investigate whether high SIRI, SII, and IPI were independent predictors of poor outcomes within 90 days, variables with P-value < 0.05 during univariate analysis were included in multivariate analysis. RESULTS: Compared with the good outcome group, the poor outcome group had higher SIRI, IPI, and SII. Spearman correlation analysis showed that the SIRI, IPI, and SII levels significantly correlated with the admission NIHSS score (r = 0.338, 0.356, 0.427, respectively; Ps < 0.001). Univariate analysis and Multivariate logistic regression analysis revealed high SIRI, SII, and IPI values as independent risk factors for poor 90-day prognosis (OR = 1.09, 1.003 and 7.109, respectively). CONCLUSIONS: High SIRI, IPI, and SII values are correlated with poor 90d outcomes in AIS patients undergoing intravenous thrombolysis.
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AVC Isquêmico , Humanos , AVC Isquêmico/tratamento farmacológico , Prognóstico , Inflamação/tratamento farmacológico , Fatores de Risco , Terapia Trombolítica , Estudos RetrospectivosRESUMO
PURPOSE: Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare vascular disease, the treatment strategies for which remain debated. This retrospective study aimed to compare the outcomes of conservative and endovascular treatments in patients with SISMAD. MATERIALS AND METHODS: Fifty-eight patients with SISMAD confirmed by computed tomography angiography admitted to our hospital between November 2017 and May 2021 and received confirmed conservative (n=43) or endovascular (n=15) treatment. The patient demographics, imaging analysis, and follow-up results were analyzed and compared. RESULTS: The cohort included 54 males and 4 females with a mean age of 52 years. Abdominal pain was the major complaint (49/58, 84.5%), followed by chest pain (2/58, 3.4%). The mean follow-up was 9.1±7.9 months. The 2 main Sakamoto types were type III (27/58, 46.6%) and type IV (16/58, 27.6%). Most patients in both groups had angle 1 (aortomesenteric angle) and angle 2 (superior mesenteric artery [SMA] course) of over 80°. About 67.3% of patients had long length of dissection (>60 mm). The median distance between the SMA root and the dissection entry site was 1.5 cm, mostly (84.5% of the patients) in the curved segment of the SMA. Telephone follow-ups found that most patients survived pain-free, and none underwent intestinal resection. Only 4 patients, 2 in each group, had recurrent abdominal pain during follow-up and received stenting treatment to achieve complete vascular remodeling. Importantly, we found that the conservative and endovascular therapies achieved similar high remodeling rates (94% and 100%, respectively; p=0.335). The conservative group achieved satisfying vascular remodeling (partial, 35%; complete, 59%), making it as safe and effective a treatment as endovascular therapy. CONCLUSIONS: Initial conservative management is safe and effective in patients with SISMAD. A high technical success rate and favorable short-term outcomes were associated with endovascular procedures as secondary interventions. It would be helpful to conduct large-scale, prospective, randomized controlled trials with long-term follow-up for SISMAD. CLINICAL IMPACT: 1. This research provided more detail clinical information, such as evaluation of abdominal pain and measurements of SMA angles, which is all relevant to treatment. 2. What's more, the most surprising results of follow-up part shown that conservative treatment could reached the remodeling rate as high as endovascular treatment, which was relatively low in other studies. It helps us share our treatment experience with clinicians. 3. In addition, we get limited knowledge about this rare disease, it's encouraging us to do more researches based on the results we had.
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OBJECTIVE: The optimal blood pressure (BP) targets for acute ischemic stroke are unclear. We aimed to assess the relationship between Mean BP and clinical outcomes during hospitalization. MATERIALS AND METHODS: We included 649 patients with Acute ischemic stroke (AIS) from December 2020 to July 2021. BP was measured daily, and mean blood pressure was calculated. Clinical events recorded within 90 days of randomization were: recurrent ischemic stroke, symptomatic intracranial hemorrhage, and death. The modified Rankin Scale (mRS) was used to measure primary outcomes 3 months after AIS. Logistic multiple regression analysis was performed by statistical software R. RESULT: There is a nonlinear U-shaped relationship between SBP and poor outcomes. This means higher SBP and lower SBP will increase the incidence of poor outcomes. The optimal mean SBP during hospitalization was 135-150 mmHg, and patients with SBP < 135mmhg OR 2.4 [95% Cl, (1.16 ~ 4.97)], P = 0.018; and > 150mmhg OR 2.04 [95% Cl, 1.02 ~ 4.08], p = 0.045 had a higher probability of poor outcomes. CONCLUSION: Our study shows that the optimal SBP of patients with AIS during hospitalization was 135-150 mmHg. The findings suggest that the relationship between mean SBP and 3-month functional outcome after AIS was U-shaped. Both higher SBP and lower SBP lead to poor prognosis in AIS patients.
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Isquemia Encefálica , Hipertensão , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Pressão Sanguínea/fisiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Isquemia Encefálica/terapia , Resultado do Tratamento , HospitalizaçãoRESUMO
PURPOSE: Metabolic syndrome (MetS) is a complex chronic disease that includes obesity and hypertension, with rising evidence demonstrating that sympathetic nervous system (SNS) activation plays a key role. Our team designed a therapeutic vaccine called ADRQß-004 targeting the α1D-adrenergic receptor (α1D-AR). This study was performed to investigate whether the ADRQß-004 vaccine improves MetS by modulating SNS activity. METHODS: C57BL/6N mice were fed a high-fat diet (HFD) and Nω-nitro-L-arginine methyl ester (L-NAME) combination diet for 18 weeks to elicit MetS. The MetS mice were subcutaneously immunized with the ADRQß-004 vaccine four times to evaluate the therapeutic efficacy in obesity and hypertension and other associated abnormalities related to MetS by conducting echocardiographic, histological, and biochemical analyses. RESULTS: The ADRQß-004 vaccine induced strong antibody production and maintained a high anti-ADR-004 antibody titer in MetS mice. The ADRQß-004 vaccine improved obesity (P < 0.001) and decreased systolic blood pressure (P < 0.001). Improvements in dysregulated glucose homeostasis and dyslipidemia resulting from the ADRQß-004 vaccine were also confirmed. Furthermore, the ADRQß-004 vaccine attenuated cardiovascular functional (P = 0.015) and structural changes (P < 0.001), decreased fat accumulation (P = 0.012) and inflammation (P = 0.050) in the epididymal white adipose tissue, and alleviated hepatic steatosis (P = 0.043) involved in MetS. Moreover, the ADRQß-004 vaccine improved systematic and visceral organs SNS activities in the MetS. CONCLUSION: This study demonstrated for the first time that the ADRQß-004 vaccine targeting α1D-AR improved obesity, hypertension, dyslipidemia, and dysglycemia, and further reduced end-organ damage, which may provide new motivation for MetS research.
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Lysine acylations are reversible and ubiquitous post-translational modifications that play critical roles in regulating multiple cellular processes. In the current study, highly abundant and dynamic acetylation, besides succinylation, was uncovered in a soil bacterium, Streptomyces coelicolor. By affinity enrichment using anti-acetyl-lysine antibody and the following LC-MS/MS analysis, a total of 1298 acetylation sites among 601 proteins were identified. Bioinformatics analyses suggested that these acetylated proteins have diverse subcellular localization and were enriched in a wide range of biological functions. Specifically, a majority of the acetylated proteins were also succinylated in the tricarboxylic acid cycle and protein translation pathways, and the bimodification occurred at the same sites in some proteins. The acetylation and succinylation sites were quantified by knocking out either the deacetylase ScCobB1 or the desuccinylase ScCobB2, demonstrating a possible competitive relationship between the two acylations. Moreover, in vitro experiments using synthetically modified peptides confirmed the regulatory crosstalk between the two sirtuins, which may be involved in the collaborative regulation of cell physiology. Collectively, these results provided global insights into the S. coelicolor acylomes and laid a foundation for characterizing the regulatory roles of the crosstalk between lysine acetylation and succinylation in the future.
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Proteínas de Bactérias/metabolismo , Lisina/metabolismo , Sirtuínas/metabolismo , Streptomyces coelicolor/metabolismo , Acetilação , Proteínas de Bactérias/genética , Redes e Vias Metabólicas , Mapas de Interação de Proteínas , Processamento de Proteína Pós-Traducional , Proteoma , Sirtuínas/genética , Streptomyces coelicolor/genética , Ácido Succínico/metabolismoRESUMO
BACKGROUND: Nutrition has become an important parameter influencing the prognosis of several cancers. However, its impact on outcomes for bladder cancer (BC) is still unclear. This review examines the association between three commonly used nutritional indices, namely, the prognostic nutritional index (PNI), controlling nutritional status (CONUT), and the geriatric nutritional risk index (GNRI) and outcomes of BC. METHODS: PubMed, CENTRAL, Scopus, Web of Science, Embase, and Google Scholar were explored for studies published up to April 13, 2023. Data from studies were pooled to examine the association between PNI, CONUT, or GNRI and overall survival (OS) and recurrence-free survival (RFS). RESULTS: Thirteen studies were included. Meta-analysis demonstrated significantly poor OS with low PNI versus high PNI in BC patients (hazard ratio [HR]: 1.71; 95% confidence interval [CI]: 1.37, 2.14; I2 = 0%). This result remained significant in various subgroup analyses. However, no association was noted between PNI and RFS (HR: 1.22; 95% CI: 0.67, 2.24; I2 = 84%). Meta-analysis showed that patients with high CONUT scores had significantly poor OS (HR: 2.43; 95% CI: 1.82, 3.25; I2 = 0%) as well as RFS (HR: 2.90; 95% CI: 2.10, 4.01; I2 = 0%). Data on GNRI were scarce and conflicting. CONCLUSION: Limited data show that PNI and CONUT are predictive of outcomes in BC. Low PNI was associated with poor OS, while high CONUT was associated with poor OS and RFS. Data on GNRI are too scarce to obtain conclusions. Further studies are needed to supplement the results.
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Avaliação Nutricional , Neoplasias da Bexiga Urinária , Humanos , Idoso , Prognóstico , Estado Nutricional , Neoplasias da Bexiga Urinária/terapia , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
As the human population grows rapidly, food shortages will become an even greater problem; therefore, increasing crop yield has become a focus of rice breeding programs. The maize gene, ZmDUF1645, encoding a putative member of the DUF1645 protein family with an unknown function, was transformed into rice. Phenotypic analysis showed that enhanced ZmDUF1645 expression significantly altered various traits in transgenic rice plants, including increased grain length, width, weight, and number per panicle, resulting in a significant increase in yield, but a decrease in rice tolerance to drought stress. qRT-PCR results showed that the expression of the related genes regulating meristem activity, such as MPKA, CDKA, a novel crop grain filling gene (GIF1), and GS3, was significantly changed in the ZmDUF1645-overexpression lines. Subcellular colocalization showed that ZmDUF1645 was primarily localized on cell membrane systems. Based on these findings, we speculate that ZmDUF1645, like the OsSGL gene in the same protein family, may regulate grain size and affect yield through the cytokinin signaling pathway. This research provides further knowledge and understanding of the unknown functions of the DUF1645 protein family and may serve as a reference for biological breeding engineering to increase maize crop yield.