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In this paper, a novel, simple and mild soft template assisted strategy and further carbonization approach has been constructed to the size-tunable preparation of porous Cu-N-C/Surfactant catalysts successfully. Note that the pluronic F127 has a significant influence on the synthesis of porous Cu-N-C/F127 with the atomically dispersed Cu-N4 and adjacent Cu atomic clusters (ACs) than other surfactants owing to their particular non-ionic structure. By combining a series of experimental analysis and density functional theory (DFT) calculations, the synergistic effects between the adjacent Cu ACs and atomically dispersed Cu-N4 are favorable for manipulating the binding energy of O2 adsorption and intermediates desorption at the atomic interface of catalysts, resulting in an excellent electrocatalytic ORR performance with a faster kinetics for Cu-N-C/F127 than those of the Cu-N-C, Cu-N-C/CTAB, Cu-N-C/SDS, and comparable with the commercial Pt/C catalyst. This method not only provides a novel approach for synthesizing highly effective copper based single atom catalysts toward ORR, but also offers an in-depth understanding of the synergisms of adjacent ACs on the Cu single atoms (SAs) for highly effective electrocatalytic ORR and Zn-air Battery.
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OBJECTIVE: To compare the clinical outcomes of using elastic intramedullary nail and plate to fix fibular fracture. METHODS: The 60 patients with tibiofibular fractures admitted from January 2015 to December 2022 were divided into two groups:intramedullary nail group and plate group, 30 cases each, intramedullary nail group was treated with elastic intramedullary nail fixation group, plate group was treated with steel plate and screw fixation group. Intramedullary nail group, there were 18 males and 12 females, aged from 22 to 75 years old with an average of (39.4±9.8) years old, including 24 cases of traffic accidents injury, 6 cases of falling injury, 23 cases of closed fractures, 7 cases of open fractures. Steel plate group, there were 15 males and 15 females, aged from 24 to 78 years old with an average of (38.6±10.2) years old. The 22 cases were injured by traffic accident, 8 cases were injured by falling. The 24 cases were closed fractures and 6 cases were open fractures. The operation time, intraoperative bleeding, American Orthopedic Foot and Ankle Society (AOFAS) ankle and hind foot scores, clinical healing time of fibula and the incidence of wound complications were compared between the two groups. RESULTS: The patients in both groups were followed up for 6 to 21 months, with an average of (14.0±2.8) months. Compared with plate group, intramedullary nail group had shorter operative time, less bleeding, shorter clinical healing time of fibula, and lower infection rate of incision, and the difference was statistically significant (P<0.05). There were 2 cases of delayed healing in intramedullary nail group, 1 case of nonunion in plate group, and 2 cases of delayed healing in plate group, and there was no statistically significant difference between the two groups (P>0.05). In the last follow-up, according to the AOFAS scoring standard, the ankle function in intramedullary nail group was excellent in 17 cases, good in 12 cases, fair in 1 case, with an average of (88.33±4.57) points, while in plate group, excellent in 16 cases, good in 10 cases, fair in 4 cases, with an average of (87.00±4.14) points;There was no statistical difference between the two groups (P>0.05). CONCLUSION: Elastic intramedullary nail has the advantages of short operation time, less intraoperative bleeding, short fracture healing time and less incision complications in the treatment of fibular fracture, which is worthy of clinical application.
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Pinos Ortopédicos , Placas Ósseas , Fíbula , Fraturas da Tíbia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Fíbula/lesões , Fíbula/cirurgia , Fraturas da Tíbia/cirurgia , Titânio , Fixação Intramedular de Fraturas/métodos , Fixação Intramedular de Fraturas/instrumentação , Adulto Jovem , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , AçoRESUMO
BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.
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Gastrite Atrófica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Úlcera Gástrica , Humanos , Mucosa Gástrica/patologia , Gastrite/diagnóstico , Gastrite/tratamento farmacológico , Gastrite/epidemiologia , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/patologia , Gastroscopia , Infecções por Helicobacter/patologia , Estilo de Vida , Dor , Úlcera Gástrica/patologiaRESUMO
Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome (IBS) with a systematic review and meta-analysis. Methods We searched MEDLINE, Embase, the Cochrane Library, Web of Science, and IEEE Xplore databases until September 2023. Cross-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were identified. We estimated the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio with a 95% confidence interval (CI), and plotted a summary receiver operating characteristic curve and evaluated the area under the curve. Results Four studies were included. The pooled diagnostic sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.94 (95% CI, 0.87-0.97), 0.89 (95% CI, 0.81-0.94), 8.43 (95% CI, 4.81-14.78), 0.07 (95% CI, 0.03-0.15), and 118.86 (95% CI, 44.18-319.75), respectively, with an area under the curve of 0.97 (95% CI, 0.95-0.98). Conclusions Computerized bowel sound analysis is a promising tool for IBS. However, limited high-quality data make the results' validity and applicability questionable. There is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis of IBS.
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Síndrome do Intestino Irritável , Síndrome do Intestino Irritável/diagnóstico , Humanos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.
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Ferroptose , Traumatismo por Reperfusão , Animais , Camundongos , Diclorodifenil Dicloroetileno , Hepatócitos , Interferon-alfa , RNA , RNA MensageiroRESUMO
Small Ras homologous guanosine triphosphatase (Rho GTPase) family proteins are highly associated with tumorigenesis and development. As intrinsic exchange activity regulators of Rho GTPases, Rho guanine nucleotide exchange factors (RhoGEFs) have been demonstrated to be closely involved in tumor development and received increasing attention. They mainly contain two families: the diffuse B-cell lymphoma (Dbl) family and the dedicator of cytokinesis (Dock) family. More and more emphasis has been paid to the Dbl family members for their abnormally high expression in various cancers and their correlation to poor prognosis. In this review, the common and distinctive structures of Dbl family members are discussed, and their roles in cancer are summarized with a focus on Ect2, Tiam1/2, P-Rex1/2, Vav1/2/3, Trio, KALRN, and LARG. Significantly, the strategies targeting Dbl family RhoGEFs are highlighted as novel therapeutic opportunities for cancer.
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Linfoma de Células B , Neoplasias , Humanos , Fatores de Troca de Nucleotídeo Guanina Rho/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , CarcinogêneseRESUMO
Severe lung injury causes basal stem cells to migrate and outcompete alveolar stem cells resulting in dysplastic repair and a loss of gas exchange function. This "stem cell collision" is part of a multistep process that is now revealed to generate an injury-induced tissue niche (iTCH) containing Keratin 5+ epithelial cells and plastic Pdgfra+ mesenchymal cells. Temporal and spatial single cell analysis reveals that iTCHs are governed by mesenchymal proliferation and Notch signaling, which suppresses Wnt and Fgf signaling in iTCHs. Conversely, loss of Notch in iTCHs rewires alveolar signaling patterns to promote euplastic regeneration and gas exchange. The signaling patterns of iTCHs can differentially phenotype fibrotic from degenerative human lung diseases, through apposing flows of FGF and WNT signaling. These data reveal the emergence of an injury and disease associated iTCH in the lung and the ability of using iTCH specific signaling patterns to discriminate human lung disease phenotypes.
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The application of oncolytic peptides has become a powerful approach to induce complete and long-lasting remission in multiple types of carcinomas, as affirmed by the appearance of tumor-associated antigens and adenosine triphosphate (ATP) in large quantities, which jumpstarts the cancer-immunity cycle. However, the ATP breakdown product adenosine is a significant contributor to forming the immunosuppressive tumor microenvironment, which substantially weakens peptide-driven oncolytic immunotherapy. In this study, a lipid-coated micelle (CA@TLM) loaded with a stapled oncolytic peptide (PalAno) and an adenosine 2A receptor (A2AR) inhibitor (CPI-444) is devised to enact tumor-targeted oncolytic immunotherapy and to overcome adenosine-mediated immune suppression simultaneously. The CA@TLM micelle accumulates in tumors with high efficiency, and the acidic tumor microenvironment prompts the rapid release of PalAno and CPI-444. Subsequently, PalAno induces swift membrane lysis of tumor cells and the release of antigenic materials. Meanwhile, CPI-444 blocks the activation of the immunosuppressive adenosine-A2AR signaling pathway. This combined approach exhibits pronounced synergy at stalling tumor growth and metastasis in animal models for triple-negative breast cancer and melanoma, providing a novel strategy for enhanced oncolytic immunotherapy.
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Maintenance of the cellular boundary between airway and alveolar compartments during homeostasis and after injury is essential to prohibit pathological plasticity which can reduce respiratory function. Lung injury and disease can induce either functional alveolar epithelial regeneration or dysplastic formation of keratinized epithelium which does not efficiently contribute to gas exchange. Here we show that Sox2 preserves airway cell identity and prevents fate changes into either functional alveolar tissue or pathological keratinization following lung injury. Loss of Sox2 in airway epithelium leads to a loss of airway epithelial identity with a commensurate gain in alveolar and basal cell identity, in part due to activation of Wnt signaling in secretory cells and increased Trp63 expression in intrapulmonary basal-like progenitors. In idiopathic pulmonary fibrosis, loss of SOX2 expression correlates with increased WNT signaling activity in dysplastic keratinized epithelium. SOX2-deficient dysplastic epithelial cells are also observed in COVID-19 damaged lungs. Thus, Sox2 provides a molecular barrier that suppresses airway epithelial plasticity to prevent acquisition of alveolar or basal cell identity after injury and help guide proper epithelial fate and regeneration.
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Astasia refers to the inability to maintain upright posture during standing, despite having full motor strength. Impairment of the vestibulocerebellar pathway, graviceptive system, and cingulate motor area have been proposed to be related to astasia. However, the responsible neural pathways remain unclear. We hypothesize that there is a common neural network behind astasia. To test the hypothesis, we reviewed all reported cases with astasia, including ours, and focused on the correlation between anatomical destruction and symptom presentation. A total of 26, including ours, non-psychogenic astasia patients were identified in the English literature. Seventy-three percent of them were associated with other neurologic symptoms and sixty-two percent of reported lesions were on the right side. Contralateral lateropulsion was very common, followed by retropulsion, when describing astasia. Infarction (54%) was the most reported cause. The thalamus (65%) was the most reported location. Infarctions were the fastest to recover (mean: 10.6 days), while lesions at the brainstem needed a longer time (mean: 61.6 days). By combining the character of lateropulsion in astasia and the presentation of an interrupted graviceptive system, we concluded that the primary graviceptive system may be the common neural network behind astasia. Future studies on astasia should focus on the pathological changes in the perception of verticality in the visual world and the body.
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AT2 cells harbor alveolar stem cell activity in the lung and can self-renew and differentiate into AT1 cells during homeostasis and after injury. To identify epigenetic pathways that control the AT2-AT1 regenerative response in the lung, we performed an organoid screen using a library of pharmacological epigenetic inhibitors. This screen identified DOT1L as a regulator of AT2 cell growth and differentiation. In vivo inactivation of Dot1l leads to precocious activation of both AT1 and AT2 gene expression during lung development and accelerated AT1 cell differentiation after acute lung injury. Single-cell transcriptome analysis reveals the presence of a new AT2 cell state upon loss of Dot1l, characterized by increased expression of oxidative phosphorylation genes and changes in expression of critical transcription and epigenetic factors. Taken together, these data demonstrate that Dot1l controls the rate of alveolar epithelial cell fate acquisition during development and regeneration after acute injury.
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Células-Tronco Adultas , Adulto , Humanos , Diferenciação Celular , Células-Tronco , Células Epiteliais Alveolares , Ciclo Celular , Histona-Lisina N-Metiltransferase/genéticaRESUMO
Accurate cell type identification is a key and rate-limiting step in single-cell data analysis. Single-cell references with comprehensive cell types, reproducible and functionally validated cell identities, and common nomenclatures are much needed by the research community for automated cell type annotation, data integration, and data sharing. Here, we develop a computational pipeline utilizing the LungMAP CellCards as a dictionary to consolidate single-cell transcriptomic datasets of 104 human lungs and 17 mouse lung samples to construct LungMAP single-cell reference (CellRef) for both normal human and mouse lungs. CellRefs define 48 human and 40 mouse lung cell types catalogued from diverse anatomic locations and developmental time points. We demonstrate the accuracy and stability of LungMAP CellRefs and their utility for automated cell type annotation of both normal and diseased lungs using multiple independent methods and testing data. We develop user-friendly web interfaces for easy access and maximal utilization of the LungMAP CellRefs.
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Perfilação da Expressão Gênica , Disseminação de Informação , Animais , Camundongos , Humanos , Análise de Célula Única , TranscriptomaRESUMO
Herein, a soft-template strategy involving the cationic surfactants has been successfully applied to size-controlled synthesis of hierarchical porous Fe-N/C for the first time. Specifically, a small amount of Fe and cationic surfactants can be uniformly doped into the zinc-based zeolite imidazole framework (ZIF-8) crystal particles and the cationic surfactants play a critical role in the formation of hierarchically porous Fe-ZIF-8@surfactant precursors. When the Fe-ZIF-8@surfactant is subsequently pyrolyzed, atomically dispersed Fe-Nx coordination structures can be in-situ converted to Fe-N/C, while the cationic surfactants decompose to form a carbon matrix to encapsulate the active sites, thereby preventing the aggregation of nanoparticles to a certain extent. As a result, the combined Fe nanocrystals and atomically dispersed Fe-Nx in the graphitic carbon matrix generate a synergistic effect to boost the electrocatalytic behaviors with a more positive half-wave potential (0.92 V) for oxygen reduction reaction (ORR) and a lower overpotential (420 mV at 10 mA cm-2) for oxygen evolution reaction (OER). As a proof of concept, the Fe-N/C@TTAB based zinc-air batteries (ZABs) present an outstanding peak power density (107.9 mW cm-2) and a superior specific capacity (706.3 mAh g-1) with robust cycling stability over 900 cycles for 150 h, which are better than the commercial Pt/C + IrO2 based ZABs.
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Type 2 diabetes mellitus(T2DM), a common chronic metabolic disease, is often accompanied by internal heat syndrome. Heat-clearing prescriptions are widely used to treat different heat syndromes of T2DM from the aspects of clearing stagnant heat, excess heat, damp heat, phlegm heat, and heat toxin, demonstrating remarkable effects. The mechanism of blood sugar-lowering agents has always been a hotspot of research. Recently, the basic studies of heat-clearing prescriptions from different perspectives have been increasing year by year. To clarify the mechanisms of heat-clearing prescriptions and find specific mechanisms, we systematically reviewed the basic studies of heat-clearing prescriptions commonly used for the treatment of T2DM in the past decade, intending to provide a reference for related research.
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Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Temperatura Alta , Medicina Tradicional Chinesa , Prescrições , SíndromeRESUMO
Colorectal cancer (CRC) is one of the top three malignant tumors in terms of morbidity, and the limited efficacy of existing therapies urges the discovery of potential treatment strategies. Immunotherapy gradually becomes a promising cancer treatment method in recent decades; however, less than 10% of CRC patients could really benefit from immunotherapy. It is pressing to explore the potential combination therapy to improve the immunotherapy efficacy in CRC patients. It is reported that Farnesoid X receptor (FXR) is deficiency in CRC and associated with immunity. Herein, we found that GW4064, a FXR agonist, could induce apoptosis, block cell cycle, and mediate immunogenic cell death (ICD) of CRC cells in vitro. Disappointingly, GW4064 could not suppress the growth of CRC tumors in vivo. Further studies revealed that GW4064 upregulated PD-L1 expression in CRC cells via activating FXR and MAPK signaling pathways. Gratifyingly, the combination of PD-L1 antibody with GW4064 exhibited excellent anti-tumor effects in CT26 xenograft models and increased CD8+ T cells infiltration, with 33% tumor bearing mice cured. This paper illustrates the potential mechanisms of GW4064 to upregulate PD-L1 expression in CRC cells and provides important data to support the combination therapy of PD-L1 immune checkpoint blockade with FXR agonist for CRC patients.
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Linfócitos T CD8-Positivos , Neoplasias Colorretais , Animais , Humanos , Camundongos , Neoplasias Colorretais/tratamento farmacológico , Imunoterapia , Receptores Citoplasmáticos e NuclearesRESUMO
PURPOSE: Ultraviolet-induced skin photoaging was involved in DNA oxidative damage. Specnuezhenide, one of the secoiridoids extracted from Ligustri Lucidi Fructus, possesses antioxidant and anti-inflammatory effects. Whether specnuezhenide ameliorates skin photoaging remains unclear. This study aimed to investigate the effect of specnuezhenide on skin photoaging induced by ultraviolet and explore the underlying mechanism. METHODS: Mice were employed to treat with ultraviolet to induce skin photoaging, then administrated 10 and 20 mg/kg of specnuezhenide. Histological analysis, protein expression, network pharmacology, and autodock analysis were conducted. RESULTS: Specnuezhenide ameliorated ultraviolet-induced skin photoaging in mice via the increase in collagen contents, and decrease in epidermal thickness, malondialdehyde content, and ß-galactosidase expression in the skin. Specnuezhenide reduced cutaneous apoptosis and inflammation in mice with skin photoaging. In addition, network pharmacology data indicated that specnuezhenide possessed potential targets on the NOD-like receptor signaling pathway. Validation experiment found that specnuezhenide inhibited the expression of NOD-like receptor family pyrin domain-containing 3, gasdermin D-C1, and Caspase 1. Furthermore, the expression of 8-Oxoguanine DNA glycosylase (OGG1), sirtuin 3 (SIRT3), and superoxide dismutase 2 was increased in specnuezhenide-treated mice with photoaging. CONCLUSION: Specnuezhenide protected against ultraviolet-induced skin photoaging in mice via a probable activation of SIRT3/OGG1 signal.
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Sirtuína 3 , Envelhecimento da Pele , Camundongos , Animais , Sirtuína 3/metabolismo , Sirtuína 3/farmacologia , Pele/patologia , Raios Ultravioleta/efeitos adversosRESUMO
Alveolar epithelial type 2 (AT2) cells harbor the facultative progenitor capacity in the lung alveolus to drive regeneration after lung injury. Using single-cell transcriptomics, software-guided segmentation of tissue damage, and in vivo mouse lineage tracing, we identified the grainyhead transcription factor cellular promoter 2-like 1 (Tfcp2l1) as a regulator of this regenerative process. Tfcp2l1 loss in adult AT2 cells inhibits self-renewal and enhances AT2-AT1 differentiation during tissue regeneration. Conversely, Tfcp2l1 blunts the proliferative response to inflammatory signaling during the early acute injury phase. Tfcp2l1 temporally regulates AT2 self-renewal and differentiation in alveolar regions undergoing active regeneration. Single-cell transcriptomics and lineage tracing reveal that Tfcp2l1 regulates cell fate dynamics across the AT2-AT1 differentiation and restricts the inflammatory program in murine AT2 cells. Organoid modeling shows that Tfcp2l1 regulation of interleukin-1 (IL-1) receptor expression controlled these cell fate dynamics. These findings highlight the critical role Tfcp2l1 plays in balancing epithelial cell self-renewal and differentiation during alveolar regeneration.
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Pulmão , Fatores de Transcrição , Animais , Camundongos , Diferenciação Celular , Regulação da Expressão Gênica , Pulmão/metabolismo , Alvéolos Pulmonares , Fatores de Transcrição/metabolismoRESUMO
During the laparoscopic Roux-en-Y gastric bypass procedure, closing mesentery or not was still controversial according to preexisted studies. So, the current meta-analysis aimed to compare the outcome of closure versus non-closure of mesenteric defects in laparoscopic Roux-en-Y gastric bypass. Fifteen studies were included, enrolling 53,488 patients. Based on the outcome of analysis, regarding internal hernia, Petersen space's IH, jejunal mesenteric's IH, hospital days, and reoperation, closure of the mesentery was better than non-closure. Besides, small bowel obstruction, anastomosis ulcer, stenosis, leakage, bleeding, gastrointestinal perforation, and postoperative BMI of patients show no difference between non-closure and closure.
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Derivação Gástrica , Hérnia Abdominal , Laparoscopia , Obesidade Mórbida , Humanos , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Hérnia Abdominal/etiologia , Hérnia Abdominal/cirurgia , Laparoscopia/métodos , Mesentério/cirurgia , Estudos RetrospectivosRESUMO
Fatty acids (FA) differ in their transfer efficiencies and metabolic partitioning and lactating cows provide a robust model to investigate kinetics of FA transport. The objective was to compare kinetics of n-3 polyunsaturated FA (PUFA) trafficking through plasma and into milk. In the first experiment, ten ruminally cannulated multiparous Holstein cows were used in a crossover design with 7 d periods. Cows were milked at 6 h intervals and abomasal treatments provided a single dose of 80.1 g of α-linolenic acid as free FA (ALA-FFA) or 45.5 g EPA and 32.9 g DHA (LCn3-FFA). Transfer of n-3 PUFA to milk was nearly 50% higher for ALA-FFA than LCn3-FFA (48.2 and 32.7% of the bolus) and fit a bi-exponential model. Rapid transport of n-3 PUFA, assumed to be directly through chylomicrons, was nearly twice as high in ALA-FFA than LCn3-FFA and the subsequent slow transport, assumed to be indirect transfer through tissue recycling, was over 2.5-fold higher in LCn3-FFA than in ALA-FFA. Plasma analysis revealed LCn3-FFA enriched phospholipids and cholesterol esters, which had a slow clearance. In the second experiment, 4 cows received a bolus of a mixture of ALA, EPA, and DHA prepartum while not lactating and around d 10, 55, and 225 of lactation. Transfer of ALA to milk did not differ between stages of lactation, but DHA was lower in early compared to mid and late lactation. In conclusion, dietary ALA is rapidly and efficiently transferred to milk in cows while EPA and DHA are rapidly incorporated into plasma or tissue fractions not available to the mammary gland. This demonstrates clear differences in trafficking and partitioning of n-3 PUFA that ultimately impact tissue and organelle enrichment with implications for effective doses.
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Ácidos Graxos Ômega-3 , Feminino , Bovinos , Animais , Ácidos Graxos Ômega-3/farmacologia , Leite , Ácidos Graxos , Lactação , Dieta , Ácidos Graxos não Esterificados , Suplementos NutricionaisRESUMO
Eravacycline (ERV) (brand name Xerava [Tetraphase]) is a new tetracycline-class antibacterial that has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treatment of complicated intra-abdominal infections (cIAIs). ETEST is a gradient diffusion method that represents a simple alternative to the broth microdilution (BMD) method for performing antimicrobial susceptibility testing (AST). A multicenter evaluation of the performance of the new ETEST ERV (bioMérieux) in comparison with BMD was conducted following FDA and International Standards Organization (ISO) recommendations, using FDA- and EUCAST-defined breakpoints. Clinical isolates of Enterobacteriaceae (n = 542) and Enterococcus spp. (n = 137) were included. Based on the BMD reference method, 92 Enterobacteriaceae isolates and 9 enterococcal isolates were nonsusceptible to ERV according to the FDA breakpoints, while 7 Escherichia coli isolates and 3 Enterococcus sp. isolates were classified as ERV resistant according the EUCAST breakpoints. Referring to FDA performance criteria, the ETEST ERV demonstrated 99.4% and 100.0% essential agreement (EA), 98.0% and 94.9% categorical agreement (CA), very major error (VME) rates of 5.4% and 33.33%, and major error (ME) rates of 1.3% and 3.1% with clinical and challenge isolates, respectively, of Enterobacteriaceae and Enterococcus spp. According to EUCAST breakpoints, E. coli and Enterococcus sp. isolate results also met ISO acceptance criteria for EA and CA (EA of 99.0% and 100.0%, respectively, and CA of 100.0% for both), without any VMEs or MEs. In conclusion, we report that ETEST ERV represents an accurate tool for performing ERV AST of Enterobacteriaceae and Enterococcus sp. isolates.