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To explore the application of seed germination biomechanical event(s) in seed vigour tests, a new procedure for the evaluation of maize seed vigour tests based on pericarp-testa rupture (PR) and coleorhiza rupture (CR) during seed germination was developed. Twenty-four lots of hybrid maize were used to determine the feasibility of the rupture test (RT) as a seed vigour test in Zea mays. The results showed that the physiological quality pattern of 24 maize seed lots assessed through RT was similar to that obtained through analysis with other seed test methods. Correlation and regression analyses revealed that the percentage of CR and percentage of PR + CR at "15 ± 0.5 °C for 120 h ± 1 h" and "20 ± 0.5 °C for 72 h ± 15 min" exhibited positive correlations with the field seedling emergence data (p < 0.01). Hence, the proposed method (the rupture test) is cogent and effective, thus providing an important reference for more crops to select for seed germination event(s) and establishing corresponding new methods for seed vigour tests in the future.
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Interobserver variations in the pathology of common astrocytic tumors impact diagnosis and subsequent treatment decisions. This study leveraged a residual neural network-50 (ResNet-50) in digital pathological images of diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma to recognize characteristic pathological features and perform classification at the patch and case levels with identification of incorrect predictions. In addition, cellularity and nuclear morphological features, including axis ratio, circularity, entropy, area, irregularity, and perimeter, were quantified via a hybrid task cascade (HTC) framework and compared between different characteristic pathological features with importance weighting. A total of 95 cases, including 15 cases of diffuse astrocytoma, 11 cases of anaplastic astrocytoma, and 69 cases of glioblastoma, were collected in Taiwan Hualien Tzu Chi Hospital from January 2000 to December 2021. The results revealed that an optimized ResNet-50 model could recognize characteristic pathological features at the patch level and assist in diagnosis at the case level with accuracies of 0.916 and 0.846, respectively. Incorrect predictions were mainly due to indistinguishable morphologic overlap between anaplastic astrocytoma and glioblastoma tumor cell area, zones of scant vascular lumen with compact endothelial cells in the glioblastoma microvascular proliferation area mimicking the glioblastoma tumor cell area, and certain regions in diffuse astrocytoma with too low cellularity being misrecognized as the glioblastoma necrosis area. Significant differences were observed in cellularity and each nuclear morphological feature among different characteristic pathological features. Furthermore, using the extreme gradient boosting (XGBoost) algorithm, we found that entropy was the most important feature for classification, followed by cellularity, area, circularity, axis ratio, perimeter, and irregularity. Identifying incorrect predictions provided valuable feedback to machine learning design to further enhance accuracy and reduce errors in classification. Moreover, quantifying cellularity and nuclear morphological features with importance weighting provided the basis for developing an innovative scoring system to achieve objective classification and precision diagnosis among common astrocytic tumors.
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Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world and can lead to severe complications in immunocompromised individuals. HEV is primarily transmitted through eating pork, which has led to an increased in anti-HEV IgG seropositivity in the general population of Europe in particular. However, it can also be transmitted intravenously, such as through transfusions. The growing evidence of HEV contamination of blood products and documented cases of transmission have given rise to practice changes and blood product screening of HEV in many European countries. This review covers the abundant European literature and focuses on the most recent data pertaining to the prevalence of HEV RNA positivity and IgG seropositivity in the North American general population and in blood products from Canada and the United States. Currently, Health Canada and the Food and Drug Administration do not require testing of HEV in blood products. For this reason, awareness among blood product prescribers about the possibility of HEV transmission through blood products is crucial. However, we also demonstrate that the province of Quebec has a prevalence of anti-HEV and HEV RNA positivity similar to some European countries. In light of this, we believe that HEV RNA blood donation screening be reevaluated with the availability of more cost-effective assays.
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Doadores de Sangue , Seleção do Doador , Vírus da Hepatite E , Hepatite E , Humanos , Hepatite E/epidemiologia , Hepatite E/diagnóstico , Hepatite E/transmissão , Canadá/epidemiologia , Estados Unidos/epidemiologia , Vírus da Hepatite E/isolamento & purificação , Vírus da Hepatite E/imunologia , Seleção do Doador/métodos , RNA Viral/sangue , Programas de Rastreamento/métodos , Prevalência , Anticorpos Anti-Hepatite/sangue , Segurança do Sangue , Imunoglobulina G/sangue , Doação de SangueRESUMO
Conventional wound dressings have poor tissue adhesion and mechanical stability, restricting their applications in dynamic motion environments. Tannic acid (TA) was ideal candidates for current dressing materials due to their well-known antioxidant and anti-inflammatory properties. However, the inevitable polymerization problem of TA limited the one-step synthesis of dressings. Herein, we reported a simple one-pot method to prepare double-network hydrogels containing N-acryloyl glycinamide (NAGA), N-hydroxyethyl acrylamide (HEAA) and TA. The resulting NHT hydrogel exhibited excellent tensile properties, fatigue resistance, and notch insensitivity to ensure mechanical stability under large deformation and stress in vitro. The NHT hydrogel also demonstrated room-temperature self-healing, broad adhesion to various substrates, synergistic swelling ability. In addition, catechol and benzene rings from TA helped shield against UV radiation and acted as free radical scavengers to relieve oxidative stress in wound damage. As a result, full-layer wounds in mice treated with NHT patches showed a higher healing rate, in which epithelialization was completed within 14 days. The integrated function enables hydrogel to maintain mechanical stability in dynamic motion environments with high strain and defects, with great potential for future clinical translation.
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OBJECT: Amplification of the epidermal growth factor receptor (EGFR) and its active mutant type III (EGFRvIII), frequently occurr in glioblastoma (GBM), contributing to chemotherapy and radiation resistance in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in EGFRvIII GBM could offer valuable insights for cancer treatment. METHODS: To elucidate the molecular mechanisms underlying EGFRvIII-mediated resistance to TMZ in GBM, we conducted a comprehensive analysis using Gene Expression Omnibus and The cancer genome atlas (TCGA) databases. Initially, we identified common significantly differentially expressed genes (DEGs) and prioritized those correlating significantly with patient prognosis as potential downstream targets of EGFRvIII and candidates for drug resistance. Additionally, we analyzed transcription factor expression changes and their correlation with candidate genes to elucidate transcriptional regulatory mechanisms. Using estimate method and databases such as Tumor IMmune Estimation Resource (TIMER) and CellMarker, we assessed immune cell infiltration in TMZ-resistant GBM and its relationship with candidate gene expression. In this study, we examined the expression differences of candidate genes in GBM cell lines following EGFRvIII intervention and in TMZ-resistant GBM cell lines. This preliminary investigation aimed to verify the regulatory impact of EGFRvIII on candidate targets and its potential involvement in TMZ resistance in GBM. RESULTS: Notably, GTPase Activating Rap/RanGAP Domain Like 3 (GARNL3) emerged as a key DEG associated with TMZ resistance and poor prognosis, with reduced expression correlating with altered immune cell profiles. Transcription factor analysis suggested Epiregulin (EREG) as a putative upstream regulator of GARNL3, linking it to EGFRvIII-mediated TMZ resistance. In vitro experiments confirmed EGFRvIII-mediated downregulation of GARNL3 and decreased TMZ sensitivity in GBM cell lines, further supported by reduced GARNL3 levels in TMZ-resistant GBM cells. CONCLUSION: GARNL3 downregulation in EGFRvIII-positive and TMZ-resistant GBM implicates its role in TMZ resistance, suggesting modulation of EREG/GARNL3 signaling as a potential therapeutic strategy.
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Gelatin has played a great potential in food preservation because of its low price and superior film forming characteristics. This review provides a comprehensive overview of the latest research progress and application of gelatin preservation technologies (film, coating, antifreeze peptide, etc.), discussing their preservation mechanisms and efficiency through the viewpoints of quality and shelf life of animal and aquatic products as well as fruits and vegetables. It showed that bioactive and intelligent gelatin-based films exhibit antibacterial, antioxidant, water resistance and pH responsive properties, making them excellent for food preservation. In addition, pH responsive properties of films also intuitively reflect the freshness of food by color. Similarly, gelatin and its hydrolysate can be widely used in antifreeze peptides to reduce the mass loss of food during freezing and extend the shelf life of frozen food. However, extensive works are still required to extend their commercial application values.
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PURPOSE: 18F-labelled somatostatin receptor (SSTR) analogs offer several advantages over 68Ga in terms of yield, cost, spatial resolution and detection rate. This study presents an interim analysis of a prospective trial designed to assess the safety, biodistribution and dosimetry of [18F]AlF-NOTA-LM3, and compare its diagnostic efficacy and clinical management outcomes with [68Ga]Ga-DOTATATE or [68Ga]Ga-NODAGA-LM3 in patients with well-differentiated NETs. METHODS: Twenty-one patients with histologically confirmed well-differentiated neuroendocrine tumors (G1 and G2) were prospectively recruited. The first eight patients underwent serial PET scans at 5, 15, 30, 45, 60, and 120 min after [18F]AlF-NOTA-LM3 injection to assess biodistribution and dosimetry. The remaining patients underwent whole-body PET/CT scans. [18F]AlF-NOTA-LM3 and [68Ga]Ga-DOTATATE PET/CT were done within a week, with a minimum 24-hour interval between the two scans. Focal uptake above the surrounding background activity and could not be explained by physiologic uptake was considered lesions of NETs. Lesion number, tumor uptake, and tumor-to-background ratio (TBR) were compared. In patients with discrepant findings, the size of the smallest lesions (measured on coregistered CT) detected on [68Ga]Ga-DOTATATE and [18F]AlF-NOTA-LM3 was compared. RESULTS: [18F]AlF-NOTA-LM3 was safe and well-tolerated. Physiological uptake of [18F]AlF-NOTA-LM3 was significantly lower than that of [68Ga]Ga-DOTATATE in abdominal organs and bone marrow, but higher in blood pool and lung. The mean effective dose was 0.024 ± 0.014 mSv/MBq. [18F]AlF-NOTA-LM3 detected significantly more liver lesions (457 vs. 291, P = 0.006) and lymph node lesions (30 vs. 22, P = 0.011) compared to [68Ga]Ga-DOTATATE. The tumor uptake was comparable, but TBR was significantly higher with [18F]AlF-NOTA-LM3 for lesions from all sites except for the duodenum. The size of the minimum liver lesions (0.54 ± 0.15 vs. 1.01 ± 0.49, P<0.001) and lymph node lesions (0.50 ± 0.19 vs. 1.26 ± 0.86, P = 0.024) detected on [18F]ALF-NOTA-LM3 were significantly smaller than those detected on [68Ga]Ga-DOTATATE. CONCLUSION: [18F]AlF-NOTA-LM3 shows favorable biodistribution, higher spatial resolution and superior performance than [68Ga]Ga-DOTATATE in detecting liver and lymph node metastases, with higher TBR. Notably, it is the first SSTR analog to show superiority in detecting lymph node lesions when compared to [68Ga]Ga-DOTATATE. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06056362.
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BACKGROUND: PRM1201 is a traditional medicine with beneficial effects against colorectal cancer (CRC) metastasis. However, the underlying mechanism of this action remains to be determined. HYPOTHESIS: Remodeling microbiota and short-chain fatty acids (SCFAs) metabolism might be a potential mechanism to explain the anti-metastatic action of PRM1201, as this gut-microbiota dependent effect involves downregulation of histone deacetylation and EMT. METHODS: To investigate this possibility, clinical specimens were sequenced and the correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFA-producing bacteria was studied. To obtain solid causal evidence, a mouse metastasis model was established to detect the influence of PRM1201 on cancer metastasis. Specifically, 16S amplicon sequencing, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, and bacterial manipulation were used to examine the gut microbiota-driven anti-metastatic action of PRM1201. RESULTS: Clinical data showed that PRM1201 increased both the number of SCFA-producing bacteria and generation of SCFAs in the feces of CRC patients. A positive correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFAs observed. The animal experiments demonstrated that PRM1201 effectively blocked CRC metastasis in a dose-dependent manner. PRM1201 treatment modulated the composition of gut microbiota, and promoted the proliferation of beneficial SCFAs producers such as Akkermansia, Lachnospiraceae_NK4A136_group and Blautia, while simultaneously reducing the abundance of pathogenic bacteria like Escherichia-Shigella. In addition, PRM1201 led to augmentation of SCFAs content. Further results indicated that the anti-cancer metastatic mechanism of PRM1201 was linked to inhibition of histone deacetylation and suppression of epithelial-to-mesenchymal transition (EMT) in metastatic lesions. Microbiota depletion treatment and fecal microbiota transplantation (FMT) underscored the microbiota-dependent nature of this phenomenon. Moreover, this anti-colorectal cancer metastatic effect and mechanism of total SCFAs and single SCFA were also confirmed. CONCLUSION: In summary, PRM1201 exerts its anti-metastatic effects by modulating SCFA-producing bacteria and enhancing the production of SCFAs. Furthermore, the prebiotic-like actions of PRM1201, along with the PRM1201-treated bacteria, function as inhibitors of histone deacetylases (DHACs) thereby effectively suppressing EMT events.
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To study the effect of starch-polyphenol interaction induced by different processing methods on digestion characteristics, a dynamic in vitro human gastrointestinal system was employed to investigate the digestive characteristics of lotus seed starch-epigallocatechin gallate (EGCG) complex (LS-EGCG) prepared by different processing methods. Digestion altered crystal structure, particle size, morphology, pH, starch hydrolysis, and EGCG content. Processing broke physical barriers, reducing particle size by enzyme erosion. Enzymatic hydrolysis gradually exposed EGCG, indicated by green fluorescence. Heat and high pressure treatments enhanced starch dissolution, increasing sugar accumulation and hydrolysis. However, ultrasonic-microwave and high pressure microfluidization treatments formed dense structures, decreasing hydrolysis rates. Overall, the complex formed by high pressure microfluidization showed better enzyme resistance. The results provide a scientific basis for the development of food with quality and functional properties.
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Catequina , Digestão , Lotus , Sementes , Amido , Lotus/química , Sementes/química , Amido/química , Amido/metabolismo , Humanos , Catequina/química , Catequina/análogos & derivados , Tamanho da Partícula , Hidrólise , Manipulação de Alimentos , Modelos Biológicos , Extratos Vegetais/químicaRESUMO
OBJECTIVE: Research shows that people with a history of mental health conditions were at increased risk of COVID-19 infection, hospitalisation, and mortality. However, the relationship between mental health conditions and COVID-19 vaccine outcomes such as vaccine intention, uptake and vaccine breakthrough is not yet well-understood. METHODS: We conducted a systematic search on the topics of COVID-19 vaccine intentions, vaccine uptake, and vaccine breakthrough, in relation to mental health conditions (e.g., depression, schizophrenia), in four databases: PubMed, MEDLINE, SCOPUS, and PsychINFO, and the publication lists of Clinical Practice Research Datalink (CPRD), The Health Improvement Network (THIN), OpenSAFELY, and QResearch. Inclusion criteria focussed on studies reporting any of the aforementioned COVID-19 vaccine outcomes among people with mental health conditions. RESULTS: Of 251 publications initially identified, 32 met our inclusion criteria. Overall, the evidence is inconclusive regarding the levels of intention to accept COVID-19 vaccines among people with mental health conditions. People with mental health conditions were more likely to have lower uptake of COVID-19 vaccines, compared to people without. Common barriers to COVID-19 vaccine uptake included concerns about the safety, effectiveness, and side effects of the vaccines. Limited evidence also suggests that vaccine breakthrough may be a particular risk for those with substance use disorder. CONCLUSIONS: Evidence for the association between COVID-19 vaccine intentions and mental health conditions is mixed. Vaccine uptake might be lower in people with mental health conditions compared to people without, yielding interventions to encourage vaccine uptake in this population. Our understanding of COVID-19 vaccine breakthrough in this population also needs enhancing.
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Vacinas contra COVID-19 , COVID-19 , Transtornos Mentais , Humanos , COVID-19/prevenção & controle , COVID-19/psicologia , Intenção , Saúde Mental , Vacinação/psicologiaRESUMO
The COVID-19 pandemic and consequent lockdowns had a substantial impact on mental health. Distress and fatigue are highly correlated. However, little is known about the determinants of fatigue in the general population during the pandemic. This study aimed to examine the prevalence and predictors of fatigue during the COVID-19 pandemic in the UK population. Online surveys were completed by a UK community cohort in April 2020 (wave 1), July-September 2020 (wave 2) and November-December 2020 (wave 3). In total, 3097 participants completed the wave 1 survey, and 1385 and 1087 participants (85.4% women) completed wave 2 and 3 surveys respectively. Fatigue was assessed using the Chalder Fatigue Scale at waves 2 and 3. Hair samples were provided by 827 participants (90.6% women) at wave 1 and wave 2, which were analyzed to indicate HairE (stress hormone). The mean total fatigue score during wave 2 was 14.7 (SD = 4.7), significantly higher than pre-pandemic levels observed in the community (mean difference 0.50, p = .003). At wave 2, 614 (44.3%) participants met the case definition for fatigue, only 15.6% of whom indicated that fatigue lasted for more than 6 months (suggesting it had started prior to the pandemic). Predictors of fatigue at wave 3 included being in a risk group, depression and belief in having COVID-19, which explained 23.8% of the variability in fatigue scores. Depression at wave 1 was the only significant predictor of remaining a fatigue case at wave 3. Fatigue was highly prevalent in the UK community during the COVID-19 pandemic and limited people's daily function. Depression and sociodemographic variables were significant predictors of fatigue.
Fatigue levels between July-December 2020 were higher compared to pre-pandemic levels.Predictors of fatigue levels 7-8 months later included being a clinical risk group, depression and belief in having had COVID-19.HairE was not associated with fatigue.Depression was the only significant predictor of remaining a fatigue case.
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COVID-19 , Fadiga , Humanos , COVID-19/epidemiologia , Fadiga/epidemiologia , Feminino , Masculino , Prevalência , Adulto , Estudos Prospectivos , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Idoso , SARS-CoV-2 , Inquéritos e Questionários , Adulto Jovem , Depressão/epidemiologia , PandemiasRESUMO
Cost-effective bulk scintillators with high density, large-area, and long-term stability are desirable for high-energy radiation detections. Conventional bulk polycrystalline or single-crystal scintillators are generally synthesized by high-temperature approaches, and it is challenging to realize simultaneously high detectivity/responsivity, spatial resolution, and rapid time response. Here, we report the cold sintering of bulk scintillators (at 90 °C) based on an "emitter-in-matrix" principle, in which emissive CsPbBr3 nanocrystals are embedded in a durable and transparent Cs4PbBr6 matrix. These bulk scintillators exhibit high light yield (33,800 photons MeV-1), low detection limit (79 nGyair s-1), fast decay time (9.8 ns), and outstanding spatial resolution of 8.9 lp mm-1 to X-ray radiation and an energy resolution of 19.3% for γ-ray (59.6 keV) detection. The composite scintillator also shows exceptional stability against environmental degradation and cyclic X-ray radiation. Our results demonstrate a cost-effective strategy for developing perovskite-based bulk transparent scintillators with exceptional performance and high radioluminescence stability for high-energy radiation detection and imaging.
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The rs72613567:TA polymorphism in 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) has been found to reduce the progression from steatosis to nonalcoholic steatohepatitis. In this study, we sought to define the pathogenic role of HSD17B13 in triggering liver inflammation. Here we find that HSD17B13 forms liquid-liquid phase separation (LLPS) around lipid droplets in the livers of nonalcoholic steatohepatitis patients. The dimerization of HSD17B13 supports the LLPS formation and promotes its enzymatic function. HSD17B13 LLPS increases the biosynthesis of platelet activating factor (PAF), which in turn promotes fibrinogen synthesis and leukocyte adhesion. Blockade of PAFR or STAT3 pathway inhibited the fibrinogen synthesis and leukocyte adhesion. Importantly, adeno-associated viral-mediated xeno-expression of human HSD17B13 exacerbated western diet/carbon tetrachloride-induced liver inflammation in Hsd17b13-/- mice. In conclusion, our results suggest that HSD17B13 LLPS triggers liver inflammation by promoting PAF-mediated leukocyte adhesion, and targeting HSD17B13 phase transition could be a promising therapeutic approach for treating hepatic inflammation in chronic liver disease.
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BACKGROUND: This study aims to explore both the toxic effects of aflatoxins (AFs) and the protective effects of degrading enzymes (DE) on broilers exposed to AFs. RESULTS: The findings reveal that a diet contaminated with 69.15 µg kg-1 of aflatoxin B1 had significant adverse effects on broilers. Specifically, it led to a reduction in average daily gain, dressed yield percentage, half-eviscerated yield with giblet yield percentage, eviscerated yield percentage, as well as serum superoxide dismutase (SOD), glutathione peroxidase activity and liver SOD activity (P < 0.05). Conversely, the diet increased the feed conversion ratio, liver index, serum glutamic oxaloacetic transaminase levels and malondialdehyde levels in both serum and liver (P < 0.05). Additionally, AFs disrupted the intestinal microflora significantly (P < 0.05), altering the relative abundance of Enterococcus, Lactobacillus and Escherichia in broiler jejunum. The addition of DE to AF-contaminated feed mitigated these negative effects and reduced the residues of aflatoxin B1, aflatoxin B2 and aflatoxin M1 in the liver and duodenum (P < 0.05). We also observed that broilers fed the diet pelleted at 80 °C exhibited improved dressing percentage and water holding capacity compared to those on the 75 °C diet. CONCLUSION: In summary, DE serves as an effective feed additive for mitigating AF contamination in poultry production. © 2024 Society of Chemical Industry.
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Aflatoxinas , Ração Animal , Bactérias , Galinhas , Contaminação de Alimentos , Microbioma Gastrointestinal , Fígado , Animais , Galinhas/metabolismo , Galinhas/crescimento & desenvolvimento , Microbioma Gastrointestinal/efeitos dos fármacos , Aflatoxinas/metabolismo , Aflatoxinas/toxicidade , Ração Animal/análise , Fígado/metabolismo , Contaminação de Alimentos/análise , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Bactérias/enzimologia , Dieta/veterinária , Masculino , Superóxido Dismutase/metabolismo , Glutationa Peroxidase/metabolismo , Aflatoxina B1/metabolismo , Aflatoxina B1/toxicidade , Malondialdeído/metabolismoRESUMO
Aconitum coreanum (A. coreanum), a traditional Chinese medicine, has been proved to treat ischemic stroke (IS). However, the mechanisms of A. coreanum's anti-stroke is currently unknown. This study aimed to uncover the effect and mechanisms of A. coreanum. And study raw Aconitum coreanum (RA) and steamed Aconitum coreanum (SA) and Aconitum coreanum processed with ginger and Alumen (GA) on the mechanism of the pharmacological action of treating IS. Determining whether the efficacy is affected after processing. The right unilateral ligation of the carotid artery of gerbils was used to mimic IS. The neurological function score, infarct volume, oxidative stress level and inflammatory factor expression were measured in gerbils after IS. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins. Metabolomic analyzes IS-related metabolic pathways in urinary metabolites. RA, SA and GA significantly improved the infarct volume and behavioral score of IS gerbils, increased the expression of brain tissue superoxide dismutase (SOD), glutathione (GSH), nitric oxide (NO) and decreased the content of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). Western blot and immunofluorescence analysis results showed that RA, SA and GA significantly increased the expression of P-Akt, PI3K, HO-1 and KEAP1. Metabolomic studies identified 112 differential metabolites, including L-Proline, Riboflavin, Leukotriene D4, and 7-Methylxanthine, as potential biomarkers of stroke, involving 14 metabolic pathways including riboflavin metabolism, pyrimidine metabolism, and purine metabolism. Our findings indicated that A. coreanum protected against cerebral ischemia injury probably via the PI3K/Akt and KEAP1/NRF2 pathway. A. coreanum before and after processing both had a protective effect against IS brain injury in gerbils. The A. coreanum efficacy was not reduced after processing. Even compared to RA, SA had better efficacy.
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Aconitum , Gerbillinae , Proteína 1 Associada a ECH Semelhante a Kelch , Fator 2 Relacionado a NF-E2 , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , AVC Isquêmico/metabolismo , AVC Isquêmico/prevenção & controleRESUMO
Obtaining information about cellular interactions is fundamental to the elucidation of physiological and pathological processes. Proximity labeling technologies have been widely used to report cellular interactions in situ; however, the reliance on addition of tag molecules typically restricts their application to regions where tags can readily diffuse, while the application in, for example, solid tissues, is susceptible. Here, we propose an "in-situ-tag-generation mechanism" and develop the GalTag technology based on galactose oxidase (GAO) for recording cellular interactions within three-dimensional biological solid regions. GAO mounted on bait cells can in situ generate bio-orthogonal aldehyde tags as interaction reporters on prey cells. Using GalTag, we monitored the dynamics of cellular interactions and assessed the targeting ability of engineered cells. In particular, we recorded, for the first time, the footprints of Bacillus Calmette-Guérin (BCG) invasion into the bladder tissue of living mice, providing a valuable perspective to elucidate the anti-tumor mechanism of BCG.
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Galactose Oxidase , Animais , Camundongos , Galactose Oxidase/metabolismo , Galactose Oxidase/química , Humanos , Comunicação CelularRESUMO
BACKGROUND: To explore the safety and feasibility of HuaXi thoracoscopic anatomical lesion resection (HX-TALR) in the treatment of congenital lung malformations (CLMs) in children. METHODS: A retrospective review of clinical data was conducted for patients who underwent HX-TALR and thoracoscopic lobectomy (TL) in our hospital from October 2017 to March 2023. Intraoperative and postoperative outcomes were compared between the HX-TALR and TL groups. RESULTS: There were 485 patients in this study, 267 of whom underwent HX-TALR and 218 of whom underwent TL. All patients underwent thoracoscopic surgery without conversion to open surgery. No patients had major complications, including bronchopleural fistula, hemorrhage, atelectasis, recurrence or reoperation. The operative time, intraoperative bleeding volume, cases with thoracic drainage tubes, postoperative hospital stay, and cases with postoperative fever in HX-TALR were greater than those in TL (P < 0.05). CONCLUSIONS: HX-TALR is safe, feasible, and retains all normal lung tissue while removing the lesion, which is expected to become the preferable operation for the treatment of CLMs. HX-TALR is a new and technically challenging procedure that needs to be carried out after training. LEVEL OF EVIDENCE: Level IV.
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Pulmão , Pneumonectomia , Toracoscopia , Humanos , Estudos Retrospectivos , Pneumonectomia/métodos , Feminino , Masculino , Toracoscopia/métodos , Lactente , Pulmão/anormalidades , Pulmão/cirurgia , Pré-Escolar , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos de Viabilidade , Criança , Resultado do Tratamento , Duração da Cirurgia , Tempo de Internação/estatística & dados numéricosRESUMO
The aim of this study was to investigate the effect of neutral protease treatment on the biochemical properties of various parts of Pacific oysters (Crassostrea gigas) under different storage conditions. The mechanism of quality degradation in the mantle, adductor muscle, gill, and trunk of treated oysters stored at -1.5 °C (superchilling) or 4 °C (refrigeration) for several days using different storage methods was studied. The results showed that the oyster treated with the enzyme exhibited higher glycogen content, flavor nucleotide content, and sensory scores compared to the control group. Superchilling at -1.5 °C was observed to slow the increase in total volatile basic nitrogen (TVB-N), total viable count (TVC), and pH, while maintaining sensory scores better than refrigeration at 4 °C. Both wet superchilling (WS) and dry exposed superchilling (DeS) methods effectively preserved freshness and quality at -1.5 °C. The freshness of the oysters' body trunk changed most significantly. K value, K' value, and AEC value, as the evaluation indexes of oyster freshness, were affected by the storage medium. Therefore, neutral protease enhances the flavor of oysters in a short time, and oysters stored in wet superchilling or dry exposed superchilling conditions have an extended shelf life.
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Orally administered "tortoiseshell and deer antler gelatin" is a common traditional medicine for patients with osteoporosis or osteoarthritis. From the pepsin-digested gelatin, we previously isolated and identified the osteoblast-stimulating pentapeptide, TSKYR. Its trypsin digestion products include the dipeptide YR, enhancing calcium ion uptake, and tripeptide TSK, resulting in remarkable 30- and 50-fold increases in mineralized nodule area and density in human osteoblast cells. These peptides were chemically synthesized in this study. The composition of deer antler preparations comprises not only proteins and peptides but also a significant quantity of metal ion salts. By analyzing osteoblast growth in the presence of peptide YR and various metal ions, we observed a synergistic effect of calcium and strontium on the effects of YR. Those peptides could also stimulate the growth of C2C12 skeletal muscle cells and human chondrocytes, increasing collagen and glycosaminoglycan content in a three-dimensional environment. The maintenance of bone homeostasis relies on a balance between osteoclasts and osteoblasts. Deer antler peptides were observed to inhibit osteoclast differentiation, as evidenced by ROS generation, tartrate-resistant acid phosphatase (TRACP) activity assays, and gene expression in RAW264.7 cells. In summary, our findings provide a deep understanding of the efficacy of this folk medicine.
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BACKGROUND: In the second-line treatment of advanced pancreatic cancer (APC), there is only one approved regimen based on the phase III NAPOLI-1 trial. However, for patients progressing after Nab-paclitaxel and Gemcitabine (Nab-P/Gem) or Nab-P combinations, second-line treatment were very limited. METHODS: This is a retrospective single-center analysis of patients. Our aim was to determine the effectiveness and tolerability of a novel regimen, gemcitabine plus Anlotinib and anti-PD1, in APC patients and to compare it with oxaliplatin, irinotecan, leucovorin, and fluorouracil (FOLFIRINOX) in the second-line setting who have failed on the first-line Nab-P combinations. RESULTS: In total, twenty-three patients received Gemcitabine plus Anlotinib and anti-PD1 in the second-line, 28 patients were treated with FOLFORINOX. There was no significant difference in overall survival (OS) or progression free survival (PFS) for either of the two sequences (p > 0.05). Patients who received Gemcitabine plus Anlotinib and anti-PD1 had a median PFS of 4.0 months (95% CI: 1.1-6.9) versus 3.5 months (95% CI 1.8-5.2) in FOLFORINOX group (p = 0.953). The median OS of Gemcitabine plus Anlotinib and anti-PD1 was 9.0 months (95% CI: 4.0-13.7) and 8.0 months (95% CI: 5.5-10.5) in FOLFORINOX group (p = 0.373). Grade ≥3 treatment-emergent adverse events (AEs) occurred for 13% of patients with Gemcitabine plus Anlotinib and anti-PD1 and 40% for FOLFORINOX. CONCLUSION: Our data confirms the effectiveness of Gemcitabine plus Anlotinib and anti-PD1 as a well-tolerated regimen in the second-line treatment of APC and extends available data on its use as a second-line treatment option when compared with FOLFIRINOX.