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BACKGROUND: Children with cerebral palsy often experience inadequate nutritional intake due to factors like anorexia, intellectual impairments, underdeveloped motor skills of the oral sensory system, and eating and swallowing disorders. These challenges not only hinder their rehabilitation but also impose various degrees of burden on society and their families. Addressing malnutrition in children with cerebral palsy has become a pressing international clinical issue. This study assessed the nutritional status of children with cerebral palsy and examined the impact of a high-calorie enteral nutrition formula as a nutritional intervention. METHODS: This retrospective study involved 132 malnourished children with cerebral palsy undergoing rehabilitation at the First People's Hospital of Yulin City from July 2020 to July 2023. Sixty-six children received conventional nutritional interventions after their parents were educated and trained in dietary practices and feeding techniques, forming the general group. The other sixty-six children were given a high-calorie intact protein or short peptide enteral nutrition formula milk powder (Nuiren JUNIOR or Peptamen Junior), and were referred to as the nutrient group. Data on anthropometric measurements, blood indicators, gross motor function, and adverse events were collected at baseline, three months, and six months. RESULTS: After 6 months of intervention, both groups showed improvements in height, weight, weight-for-height Z-score, weight-for-age Z-score and gross motor function. There were statistical differences in height change, body mass index-for-age Z-score, and gross motor function between the two groups (P<0.05). The efficiency of nutritional intervention was significantly higher in the nutrient group than in the general group (P<0.05). In addition, total albumin, albumin, prealbumin, and 25-hydroxyvitamin D levels were higher in the nutrient group than in the general group (P<0.05). An incidence of side effects was observed in 15.15% of the children in the general group and 9.09% in the nutrient group, without significant difference (χ2=1.138, P=0.286). CONCLUSION: High-calorie whole protein or peptide nutritional formulas can significantly improve malnutrition and enhance gross motor function development in children with cerebral palsy and has a low incidence of adverse events. These interventions hold promise for broader clinical application.
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AIMS: Coronary heart disease (CHD) patients with changed serum soluble receptor for advanced glycation end products (sRAGE) will experience microalbuminuria and even kidney dysfunction. However, the role of sRAGE for microalbuminuria in CHD is still not established. This study aimed to evaluate the association between sRAGE and early kidney dysfunction in CHD patients. MATERIALS AND METHODS: In this cross-sectional study, sRAGE and urinary albumin-to-creatinine ratio (uACR) were measured in hospitalized CHD patients who have undergone coronary arteriography to evaluate the distinction and correlation between sRAGE and uACR. RESULTS: There were 127 CHD patients (mean age: 63.06⯱â¯10.93 years, 93 males) in the study, whose sRAGE were 1.83⯱â¯0.64⯵g/L. The sRAGE level was higher in kidney injury group (uACRâ¯≥â¯30â¯mg/g) compared with no kidney injury group (uACRâ¯<â¯30â¯mg/g) [(2.08⯱â¯0.70 vs. 1.75⯱â¯0.61) µg/L, Pâ¯<â¯0.05]. Moreover, the positive correlation between serum sRAGE and uACR was significant in CHD patients (râ¯=â¯0.196, Pâ¯<â¯0.05). Binary logistic regression suggests sRAGE as a predictor for microalbuminuria in CHD patients [Odd Ratioâ¯=â¯2.62 (1.12-6.15), Pâ¯<â¯0.05)]. The area under the receiver operating characteristic curve (AUC) of sRAGE is higher than that of the traditional indicators of renal function such as creatinine and estimated glomerular filtration rate, indicating sRAGE might have a good performance in evaluating early kidney injury in CHD patients [AUC is 0.660 (0.543-0.778), Pâ¯<â¯0.01)]. CONCLUSIONS: Serum sRAGE was positively correlated to uACR and might serve as a potential marker to predict early kidney injury in CHD patients.
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AIM: To prevent neovascularization in diabetic retinopathy (DR) patients and partially control disease progression. METHODS: Hypoxia-related differentially expressed genes (DEGs) were identified from the GSE60436 and GSE102485 datasets, followed by gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Potential candidate drugs were screened using the CMap database. Subsequently, a protein-protein interaction (PPI) network was constructed to identify hypoxia-related hub genes. A nomogram was generated using the rms R package, and the correlation of hub genes was analyzed using the Hmisc R package. The clinical significance of hub genes was validated by comparing their expression levels between disease and normal groups and constructing receiver operating characteristic curve (ROC) curves. Finally, a hypoxia-related miRNA-transcription factor (TF)-Hub gene network was constructed using the NetworkAnalyst online tool. RESULTS: Totally 48 hypoxia-related DEGs and screened 10 potential candidate drugs with interaction relationships to upregulated hypoxia-related genes were identified, such as ruxolitinib, meprylcaine, and deferiprone. In addition, 8 hub genes were also identified: glycogen phosphorylase muscle associated (PYGM), glyceraldehyde-3-phosphate dehydrogenase spermatogenic (GAPDHS), enolase 3 (ENO3), aldolase fructose-bisphosphate C (ALDOC), phosphoglucomutase 2 (PGM2), enolase 2 (ENO2), phosphoglycerate mutase 2 (PGAM2), and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). Based on hub gene predictions, the miRNA-TF-Hub gene network revealed complex interactions between 163 miRNAs, 77 TFs, and hub genes. The results of ROC showed that the except for GAPDHS, the area under curve (AUC) values of the other 7 hub genes were greater than 0.758, indicating their favorable diagnostic performance. CONCLUSION: PYGM, GAPDHS, ENO3, ALDOC, PGM2, ENO2, PGAM2, and PFKFB3 are hub genes in DR, and hypoxia-related hub genes exhibited favorable diagnostic performance.
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BACKGROUND: Ear keloids, often resulting from ear piercing or other traumas, significantly alter appearance, adversely impacting patients' quality of life and psychological well-being. Thus, developing an effective and esthetically pleasing surgical repair technique is crucial for enhancing patient quality of life. METHODS: This study introduces a novel tripartite surgical approach, which includes arcuate incision design, blind dissection for scar flap, and centrifugal keloid core serial shave excision (ABC for short). This technique is particularly suited for keloids induced by ear piercing that are inoperable for direct suturing or where direct suturing significantly alters the ear contour. RESULTS: In this study, 17 patients underwent the surgical treatment without observing special complications such as infection or necrosis. Long-term postoperative follow-up demonstrated good restoration of the ear contour, with only one case of recurrence. Patients expressed satisfaction with both the surgical process and outcomes. CONCLUSIONS: The triple surgical technique (ABC surgery method) for treating auricular keloids has demonstrated excellent repair results, significantly improving auricle shape. Despite relying on the surgeon's experience, keloid characteristics, and patient comorbidities, it provides an effective treatment option. When combined with local radiotherapy, the recurrence rate is also significantly controlled. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Despite significant progress in therapy, there remains a lack of substantial evidence regarding the molecular factors that lead to renal fibrosis. Neuraminidase 4 (NEU4), an enzyme that removes sialic acids from glycoconjugates, has an unclear role in chronic progressive fibrosis. Here, this study finds that NEU4 expression is markedly upregulated in mouse fibrotic kidneys induced by folic acid or unilateral ureter obstruction, and this elevation is observed in patients with renal fibrosis. NEU4 knockdown specifically in the kidney attenuates the epithelial-to-mesenchymal transition, reduces the production of pro-fibrotic cytokines, and decreases cellular senescence in male mice. Conversely, NEU4 overexpression exacerbates the progression of renal fibrosis. Mechanistically, NEU4254-388aa interacts with Yes-associated protein (YAP) at WW2 domain (231-263aa), promoting its nucleus translocation and activation of target genes, thereby contributing to renal fibrosis. 3,5,6,7,8,3',4'-Heptamethoxyflavone, a natural compound, is identified as a novel NEU4 inhibitor, effectively protecting mice from renal fibrosis in a NEU4-dependent manner. Collectively, the findings suggest that NEU4 may represent a promising therapeutic target for kidney fibrosis.
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The removal of mis-incorporated nucleotides by proofreading activity ensures DNA replication fidelity. Whereas the ε-exonuclease DnaQ is a well-established proofreader in the model organism Escherichia coli, it has been shown that proofreading in a majority of bacteria relies on the polymerase and histidinol phosphatase (PHP) domain of replicative polymerase, despite the presence of a DnaQ homolog that is structurally and functionally distinct from E. coli DnaQ. However, the biological functions of this type of noncanonical DnaQ remain unclear. Here, we provide independent evidence that noncanonical DnaQ functions as an additional proofreader for mycobacteria. Using the mutation accumulation assay in combination with whole-genome sequencing, we showed that depletion of DnaQ in Mycolicibacterium smegmatis leads to an increased mutation rate, resulting in AT-biased mutagenesis and increased insertions/deletions in the homopolymer tract. Our results showed that mycobacterial DnaQ binds to the ß clamp and functions synergistically with the PHP domain proofreader to correct replication errors. Furthermore, the loss of dnaQ results in replication fork dysfunction, leading to attenuated growth and increased mutagenesis on subinhibitory fluoroquinolones potentially due to increased vulnerability to fork collapse. By analyzing the sequence polymorphism of dnaQ in clinical isolates of Mycobacterium tuberculosis (Mtb), we demonstrated that a naturally evolved DnaQ variant prevalent in Mtb lineage 4.3 may enable hypermutability and is associated with drug resistance. These results establish a coproofreading model and suggest a division of labor between DnaQ and PHP domain proofreader. This study also provides real-world evidence that a mutator-driven evolutionary pathway may exist during the adaptation of Mtb.
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Replicação do DNA , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , MutaçãoRESUMO
Despite the large-scale adoption of Artificial Intelligence (AI) models in healthcare, there is an urgent need for trustworthy tools to rigorously backtrack the model decisions so that they behave reliably. Counterfactual explanations take a counter-intuitive approach to allow users to explore "what if" scenarios gradually becoming popular in the trustworthy field. However, most previous work on model's counterfactual explanation cannot generate in-distribution attribution credibly, produces adversarial examples, or fails to give a confidence interval for the explanation. Hence, in this paper, we propose a novel approach that generates counterfactuals in locally smooth directed semantic embedding space, and at the same time gives an uncertainty estimate in the counterfactual generation process. Specifically, we identify low-dimensional directed semantic embedding space based on Principal Component Analysis (PCA) applied in differential generative model. Then, we propose latent space smoothing regularization to rectify counterfactual search within in-distribution, such that visually-imperceptible changes are more robust to adversarial perturbations. Moreover, we put forth an uncertainty estimation framework for evaluating counterfactual uncertainty. Extensive experiments on several challenging realistic Chest X-ray and CelebA datasets show that our approach performs consistently well and better than the existing several state-of-the-art baseline approaches.
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Dissolved organic matter ï¼DOMï¼ plays an important role in indicating the pollution of the water environment, and sediment is the main source of endogenous pollution of the water environment. Research on the spectral characteristics of DOM in sediments was important for the interpretation of water environment pollution. In this study, UV-visible absorption spectroscopy and three-dimensional fluorescence spectroscopy combined with the parallel factor analysis ï¼PARAFACï¼ were used to analyze the fluorescent components, sources, and influencing factors of DOM in sediments from the Yuanhe River Basin. The results showed that the average of ωï¼TNï¼, ωï¼TPï¼, and ωï¼OMï¼ in sediments from the Yuanhe River Basin were 0.52, 0.66, and 21.22 g·kg-1, respectively. The concentrations of total nitrogen and total phosphorus increased along the flow direction. In addition, the sediment DOM from the Yuanhe River Basin mainly originated from terrestrial sources. The chromophoric DOM concentration and aromaticity of DOM from the downstream reaches were significantly higher than those from the upstream and midstream reaches. Based on PARAFAC, four fluorescent components of DOM in sediments from the Yuanhe River Basin were identified, including three humus-like components ï¼C1, C3, and C4ï¼ and one protein-like component ï¼C2ï¼. The sediment DOM was dominated by humus-like materials. Moreover, the fluorescent intensity of the fluorescent components was higher in the downstream reaches. Redundancy analysis revealed that the physicochemical properties of sediments in the mainstream and downstream reaches played a more significant role in the spectral properties of DOM. Phosphorus pollution and the terrestrial humus-like substance of sediment DOM were homologous. These results indicated that the spectral properties of DOM were the indicator of water environmental pollution in the region with strong anthropogenic influence.
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ABC transporters are a highly conserved membrane protein class that promote the transport of substances across membranes. Under drought conditions, insects primarily regulate the content of cuticular hydrocarbon (CHC) to retain water and prevent evaporative loss. Involvement of ABC transporter protein G (ABCG) subfamily genes in insect CHC transport has been relatively understudied. In this study, we demonstrated that ABCG4 gene in Acyrthosiphon pisum (ApABCG4) is involved in CHC transport and affects drought tolerance by regulating CHC accumulation. ApABCG4 is strongly expressed in the abdominal cuticle and embryonic stages of A. pisum. Effective silencing of ApABCG4 was achieved using RNAi, and the silencing duration was analyzed. ApABCG4 silencing resulted in a significant decrease in the total and component contents of the CHC and cuticular waxy coatings of A. pisum. Nevertheless, the internal hydrocarbon content remained unchanged. The lack of cuticular hydrocarbons significantly reduced the drought tolerance of A. pisum, shortening its survival time under drought stress. Drought stress caused significant upregulation of ApABCG4. Molecular docking showed that ApABCG4 has a high binding affinity for nine n-alkanes of CHC through electrostatic interactions. These results indicate that ApABCG4 is a novel RNAi target with key applications in aphid biological control.
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N-oxides play a pivotal role in natural products and emerging drug design, while also serving as valuable ligand scaffolds in organometallic chemistry. Among heteroatom oxidations, the conversion of amines to N-oxides is a critical and challenging facet. We present here a highly enantioselective N-oxidation methodology for both cyclic and acyclic amines. The method employs an ion-pair catalyst comprising a chiral bisguanidinium [BG]2+ cation and an achiral oxodiperoxomolybdosulfate anion [(µ-SO4)2Mo2O2(µ-O2)2(O2)2]2-. Notably, the bisguanidinium cation undergoes modification through silyl group incorporation and is elucidated by X-ray crystallography. Our findings underscore the crucial role of the side chain in the determination of the chiral pocket size, allowing for the oxidation of diverse tertiary amines with enantioselectivities. Comprehensive mechanistic investigations are conducted to explain the catalytic system's efficacy in achieving dynamic kinetic resolution (DKR) with high efficiency.
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BACKGROUND: Central nervous system involvement in chronic lymphocytic leukemia rarely occurs, and there is no standard therapy for central nervous system involvement in chronic lymphocytic leukemia. This article aims to analyze the diagnosis and treatment of central nervous system involvement in chronic lymphocytic leukemia. CASE PRESENTATION: It reports two cases of central nervous system involvement in chronic lymphocytic leukemia describing the clinical course, therapy, and prognosis. Case 1 is a 67-year-old Asian male patient, he experienced complications with central nervous system involvement after developing resistance to ibrutinib, bendamustine, and rituximab (BR) chemotherapies. The central nervous system lesion was controlled with high-dose methotrexate combined with pomalidomide, but Richter transformation occurred several months later. Case 2 is a 62-year-old Asian female patient, she had central nervous system involvement at initial diagnosis, and bone marrow and central nervous system lesions were controlled by ibrutinib therapy. CONCLUSION: Central nervous system involvement in chronic lymphocytic leukemia is rare and can be diagnosed on the basis of clinical features, cerebrospinal fluid testing, and radiographic evaluation. Ibrutinib, pomalidomide, and other drugs that can cross the blood-brain barrier may be effective for treating central nervous system involvement in chronic lymphocytic leukemia.
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Adenina , Leucemia Linfocítica Crônica de Células B , Piperidinas , Talidomida , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Adenina/análogos & derivados , Piperidinas/uso terapêutico , Talidomida/uso terapêutico , Talidomida/análogos & derivados , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Pirazóis/uso terapêutico , Metotrexato/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pirimidinas/uso terapêuticoRESUMO
Ursolic acid has gradually attracted much attention due to its unique pharmacological activities and valuable market value in recent years. Currently, ursolic acid is mostly extracted from loquat leaves, but the plant extraction method has low yield and high cost, and chemical synthesis is not readily available, so the biosynthesis method provides a new source for ursolic acid. α-amyrin acts as the main precursor for the synthesis of ursolic acid, and its yield is positively correlated with ursolic acid yield. Oxidosqualene cyclase(OSC) belongs to a multigene family which can catalyze the common precursor 2,3-oxidosqualene to generate different types of triterpene backbones, and plays a decisive role in the synthesis of triterpenoids. However, there are fewer reported key genes catalyzing the synthesis of α-amyrin in medicinal plants, and the yield and proportion of α-amyrin in the catalyzed products have always been a focus of research. In this study, ItOSC2, MdOSC1, AaOSC2 and CrAS, four enzymes capable of catalyzing the production of α-amyrin from 2,3-oxidosqualene, were cloned from Iris tectorum, Malus domestica, Artemisia annua and Catharanthus roseus, subject to sequence alignment and phylogenetic tree analyses, and transformed into Saccharomyces cerevisiae as plasmids. After 7 days of fermentation, the yield and proportions of α-amyrin, ß-amyrin and ergosterol were measured. Finally, AaOSC2 with the best ability to catalyze the generation of α-amyrin was filtered out, providing a key gene element for the later construction of engineered yeast strains with high production of α-amyrin and ursolic acid.
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Transferases Intramoleculares , Ácido Oleanólico , Transferases Intramoleculares/genética , Transferases Intramoleculares/metabolismo , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/metabolismo , Ácido Oleanólico/química , Ácido Oleanólico/biossíntese , Clonagem Molecular , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Triterpenos/metabolismo , Triterpenos/química , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/metabolismo , Filogenia , Triterpenos PentacíclicosRESUMO
Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.
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Carcinoma de Células Renais , Neoplasias Renais , Recidiva Local de Neoplasia , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Feminino , Recidiva Local de Neoplasia/genética , Pessoa de Meia-Idade , Idoso , Prognóstico , Genômica/métodos , Adulto , Estadiamento de Neoplasias , Aprendizado Profundo , Intervalo Livre de DoençaRESUMO
The efficient and complete extraction of uranium from aqueous solutions is crucial for safeguarding human health from potential radiotoxicity and chemotoxicity. Herein, an ultrathin 2D metal-organic framework (MOF) nanosheet with cavity structures was elaborately constructed, based on a calix[4]arene ligand. The large molecular skeleton and cup-shaped feature of the calix[4]arene enabled the as-prepared MOFs with large layer separations, which can be readily delaminated into ultrathin single-layer (â¼1.25 nm) nanosheets. The incorporation of permanent cavity structures to the MOF nanosheets can fully utilize their structural features of readily accessible adsorption groups and exposed surface area in uranium removal, reaching ultrafast adsorption kinetics; the functionalized cavity structure endowed MOF nanosheets with the ability to preconcentrate and extract uranium from aqueous solutions with ultrahigh efficiencies, even at extremely low concentrations. As a result, relatively high removal ratios (>95%) can be achieved for uranium within 5 min, even in the ultralow concentration range of 75-250 ppb, and the residual uranium was reduced to below 4.9 ppb. The MOF nanosheets also exhibited extremely high anti-interference ability, which could efficiently remove the low-level uranium (â¼150 ppb) from various real samples. The characterizations and density functional theory calculations demonstrated that the synergistic effects of multiple interactions between the carboxylate groups and cage-like cavities with uranyl ions can be responsible for the efficient and selective uranium extraction.
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Co-activation signal that induces/sustains pleiotropic effector functions of antigen-specific γδ T cells remains unknown. Here, Mycobacteria tuberculosis (Mtb) tuberculin administration during tuberculosis (TB) skin test resulted in rapid expression of co-activation signal molecules CD137 and CD107a by fast-acting Vγ2Vδ2 T cells in TB-resistant subjects (Resisters), but not patients with active TB. And, anti-CD137 agonistic antibody treatment experiments showed that CD137 signaling enabled Vγ2Vδ2 T cells to produce more effector cytokines and inhibit intracellular Mtb growth in macrophages (Mɸ). Consistently, Mtb antigen (Ag) HMBPP stimulation induced sustainable high-level CD137 expression in fresh and activated Vγ2Vδ2 T cells from uninfected subjects, but not TB patients. CD137+Vγ2Vδ2 T-cell subtype predominantly displayed central memory phenotype and mounted better proliferative responses than CD137-Vγ2Vδ2 T-cells. In response to HMBPP, CD137+Vγ2Vδ2 T-cell subtype rapidly differentiated into greater numbers of pleiotropic effector cells producing anti-Mtb cytokines compared to CD137-Vγ2Vδ2 T subtype, with the non-canonical NF-κB pathway involved. CD137 expression in Vγ2Vδ2 T cells appeared to signal anti-Mtb effector functions leading to intracellular Mtb growth inhibition in Mɸ, and active TB disrupted such CD137-driven anti-Mtb effector functions. CD137+Vγ2Vδ2 T-cells subtype exhibited an epigenetic-driven high-level expression of GM-CSF and de novo production of GM-CSF critical for Vγ2Vδ2 T-cell controlling of Mtb growth in MÏ. Concurrently, exosomes produced by CD137+Vγ2Vδ2 T cells potently inhibited intracellular mycobacterial growth. Furthermore, adoptive transfer of human CD137+Vγ2Vδ2 T cells to Mtb-infected SCID mice conferred protective immunity against Mtb infection. Thus, our data suggest that CD137 expression/signaling drives pleiotropic γδ T-cell effector functions that inhibit intracellular Mtb growth.
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Mycobacterium tuberculosis , Transdução de Sinais , Tuberculose , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Humanos , Mycobacterium tuberculosis/imunologia , Transdução de Sinais/imunologia , Tuberculose/imunologia , Tuberculose/microbiologia , Camundongos , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Feminino , Animais , Macrófagos/imunologia , Masculino , Adulto , Antígenos de Bactérias/imunologia , Citocinas/metabolismo , Citocinas/imunologia , Ativação Linfocitária/imunologia , Camundongos SCIDRESUMO
BACKGROUND: White matter lesions (WMLs) are increasingly linked to the pathological process of chronic vascular dementia (VaD). An effective crocins fraction extracted from Gardenia Fructus, GJ-4, has been shown to improve cognitive function in several Alzheimer's disease models and VaD models. OBJECTIVES: To explore the potential mechanisms of GJ-4 on WMLs in a chronic VaD mouse model. METHODS: The chronic VaD mouse model was established, and WMLs were characterized by cerebral blood flow (CBF), behavioral tests, LFB staining, and immunohistochemistry. The anti-oxidative effect of GJ-4 was validated by examining biochemical parameters (SOD, MDA, and GSH) and the Keap1-Nrf2/HO-1 pathway. The impact of GJ-4 on lipid metabolism in WM was further investigated through lipidomic analysis. RESULTS: GJ-4 significantly attenuated cognitive impairments and improved the CBF of BCAS (bilateral common carotid artery stenosis)-induced mice. Mechanism research showed that GJ-4 could enhance cognition by promoting the repair of WMLs by inhibiting oxidative stress. Furthermore, GJ-4 treatment significantly reduced chronic cerebral hypoperfusion (CCH)-induced WMLs via improving lipid metabolism disorder in the WM. CONCLUSION: This research has provided valuable insights into the significance of WMLs in CCH-induced VaD and underscored the potential of GJ-4 as a therapeutic agent for improving cognitive function by targeting WMLs. These findings suggest that GJ-4 is a promising candidate for the treatment of VaD.
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Disfunção Cognitiva , Demência Vascular , Modelos Animais de Doenças , Fármacos Neuroprotetores , Estresse Oxidativo , Substância Branca , Animais , Demência Vascular/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Masculino , Substância Branca/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Gardenia/química , Camundongos Endogâmicos C57BL , Carotenoides/farmacologia , Carotenoides/uso terapêutico , Circulação Cerebrovascular/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/farmacologiaRESUMO
Vitamin C (Ascorbic acid, AA), as vital micro-nutrient, plays an essential role for male animal reproduction. Previously, we showed that vitamin C reprogrammed the transcriptome and proteome to change phenotypes of porcine immature Sertoli cells (iSCs). Here, we used LC-MS-based non-targeted metabolomics to further investigate the metabolic effects of vitamin C on porcine iSCs. The results identified 43 significantly differential metabolites (DMs) (16 up and 27 down) as induced by vitamin C (L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate, AA2P) treatment of porcine iSCs, which were mainly enriched in steroid related and protein related metabolic pathways. ELISA (Enzyme-Linked ImmunoSorbent Assay) showed that significantly differential metabolites of Dehydroepiandrosterone (DHEA) (involved in steroid hormone biosynthesis) and Desmosterol (involved in steroid degradation) were significantly increased, which were partially consistent with metabolomic results. Further integrative analysis of metabolomics, transcriptomics and proteomics data identified the strong correlation between the key differential metabolite of Dehydroepiandrosterone and 6 differentially expressed genes (DEGs)/proteins (DEPs) (HMGCS1, P4HA1, STON2, LOXL2, EMILIN2 and CCN3). Further experiments validated that HMGCS1 could positively regulate Dehydroepiandrosterone level. These data indicate that vitamin C could modulate the metabolism profile, and HMGCS1-DHEA could be the pathway to mediate effects exerted by vitamin C on porcine iSCs.
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Ácido Ascórbico , Desidroepiandrosterona , Células de Sertoli , Animais , Masculino , Ácido Ascórbico/farmacologia , Ácido Ascórbico/metabolismo , Suínos , Células de Sertoli/metabolismo , Células de Sertoli/efeitos dos fármacos , Desidroepiandrosterona/farmacologia , Desidroepiandrosterona/metabolismo , Células Cultivadas , Metabolômica/métodosRESUMO
This study aims to compare the perioperative, oncological, and functional outcomes of perineal hydrodissection (HD) with standard treatment (ST) in patients undergoing robot-assisted radical prostatectomy. We performed an exhaustive search in databases such as PubMed, Embase, Web of Science, and the Cochrane Library, seeking English-language studies relevant to our research question, with a cutoff date of April 2024. The pooled results were assessed using the weighted mean differences (WMDs), standardized mean differences (SMDs), and odds ratios (ORs) metrics. We also performed a sensitivity analysis. The meta-analysis was conducted utilizing Stata/MP version 18 software. The study was registered with PROSPERO (ID: CRD 42024536400). We included a total of five studies (three RCTs and two retrospective studies). According to the data from the Meta-analysis, the HD group showed positive effects in promoting urinary continence (OR 2.64, 95% CI 1.36, 5.12; p = 0.004 < 0.05) and erectile function (SMD 0.92, 95%CI 0.56, 1.27; p < 0.05) within 3 months after surgery. However, no notable disparities were observed in terms of operative time, estimated blood loss, bilateral nerve-sparing rate, or the rate of positive surgical margin. Perineal hydrodissection can be safely applied in robot-assisted radical prostatectomy (RARP), offering a distinct advantage in functional outcomes compared to those who undergo standard robot-assisted prostatectomy alone.
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Períneo , Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Prostatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Períneo/cirurgia , Neoplasias da Próstata/cirurgia , Resultado do Tratamento , Incontinência Urinária/etiologia , Complicações Pós-Operatórias/etiologiaRESUMO
To investigate Gyrodactylus infection of fish in the river system of Xinjiang (China), Gyrodactylus individuals were isolated from specimens of Diptychus maculatus. Morphological characterization and phylogenetic analysis based on ITS1-5.8S-ITS2 rDNA locus revealed that the gyrodactylids belong to new species. Gyrodactylus diptychi n. sp. differs significantly in the morphology of the haptoral structures from 12 known species of Gyrodactylus found in fishes of the subfamily Schizothoracinae. In particular, G. diptychi n. sp. has a relatively short dorsal bar with thick and large ends, flat and straight hamuli roots, and small ventral bar processes. Furthermore, G. diptychi n. sp. is the only representative of Gyrodactylus found on D. maculatus. Using the BLASTn search of ITS1-5.8S-ITS2 rDNA sequences in GenBank and the Bayesian Information and Maximum Likelihood methods, we constructed phylogenetic trees for G. diptychi n. sp. As a result, our studies clearly identified that G. diptychi n. sp. was the first Gyrodactylus monogenean isolated from D. maculatus and a new species belonged to the subgenus Limnonephrotus.
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The purpose of this study was to conduct a comparative analysis of the perioperative outcomes associated with robot-assisted laparoscopic prostatectomy (RARP) versus open radical prostatectomy (ORP) in the obese population diagnosed with prostate cancer. We performed a comprehensive search in key databases such as PubMed, Embase, Web of Science, and the Cochrane Library, encompassing studies of all languages, with a final search date of April 2024. We also omitted articles that consisted of conference abstracts and content that was not pertinent to our study. The aggregated outcomes were evaluated utilizing the metrics of weighted mean differences (WMDs) and odds ratios (ORs). A sensitivity analysis was also integrated into our assessment. The meta-analysis was facilitated by employing Stata/MP version 18 software. Additionally, the study was duly registered with PROSPERO under the identifier: CRD 42024540216. This meta-analysis, which included five trials, shows that compared to ORP, RARP is associated with a reduced estimated blood loss (EBL) (WMD -445.77, 95%CI -866.08, -25.45; p = 0.038), a decreased transfusion rate (OR 0.17, 95%CI 0.13, 0.21; p < 0.001), and a diminished overall complication rate (OR 0.71, 95%CI 0.58, 0.86; p = 0.001). No statistically significant differences were found in operative time (OT) (WMD 1.88, 95%CI -46.53, 50.28; p = 0.939) or length of stay (LOS) (WMD -0.41, 95%CI -1.07, 0.25; p = 0.221). Among patients with obesity and prostate cancer, RARP demonstrates advantages over ORP by reducing estimated blood loss, transfusion requirements, and the incidence of complications. Notably, there were no significant differences in operative duration and hospital stay between the two surgical approaches. These findings suggest that RARP could be a preferable surgical option for obese individuals with prostate cancer.