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1.
World J Gastrointest Surg ; 16(8): 2503-2510, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39220053

RESUMEN

BACKGROUND: The effect of the number of lymph node dissections (LNDs) during radical resection for colorectal cancer (CRC) on overall survival (OS) remains controversial. AIM: To investigate the association between the number of LNDs and OS in patients with tumor node metastasis (TNM) stage I-II CRC undergoing radical resection. METHODS: Patients who underwent radical resection for CRC at a single-center hospital between January 2011 and December 2021 were retrospectively analyzed. Cox regression analyses were performed to identify the independent predictors of OS at different T stages. RESULTS: A total of 2850 patients who underwent laparoscopic radical resection for CRC were enrolled. At stage T1, age [P < 0.01, hazard ratio (HR) = 1.075, 95% confidence interval (CI): 1.019-1.134] and tumour size (P = 0.021, HR = 3.635, 95%CI: 1.210-10.917) were independent risk factors for OS. At stage T2, age (P < 0.01, HR = 1.064, 95%CI: 1.032-1.098) and overall complications (P = 0.012, HR = 2.297, 95%CI: 1.200-4.397) were independent risk factors for OS. At stage T3, only age (P < 0.01, HR = 1.047, 95%CI: 1.027-1.066) was an independent risk factor for OS. At stage T4, age (P < 0.01, HR = 1.057, 95%CI: 1.039-1.075) and body mass index (P = 0. 034, HR = 0.941, 95%CI: 0.890-0.995) were independent risk factors for OS. However, there was no association between LNDs and OS in stages I and II. CONCLUSION: The number of LDNs did not affect the survival of patients with TNM stages I and II CRC. Therefore, insufficient LNDs should not be a cause for alarm during the surgery.

2.
Nephrology (Carlton) ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39254037

RESUMEN

AIM: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Pregnant IgAN patients are more susceptible to adverse pregnancy outcomes (APO). However, the risk factor for APO and its effects on the long-term renal outcome of pregnant IgAN patients remained unclear. METHODS: We performed a retrospective observational study covering 2003-2019 that included 44 female IgAN patients with pregnancy history to investigate the risk factor for APO and its impact on clinical outcome in IgAN. Renal function outcome and proteinuria remission were evaluated in pregnant IgAN women with and without APO. RESULTS: In this retrospective and observational study, we found that patients with APO exhibited higher levels of serum creatinine and IgM, and lower haemoglobin levels while other clinical characteristics, pathological characteristics and therapy protocol had no significant difference. We found that anaemia and a higher level of serum IgM were independent risk factors for APO. IgAN pregnant women without APO experienced a higher proportion of proteinuria remission than those with APO, but there is no difference in the renal function outcome. CONCLUSION: Pregnant IgAN patients with higher risks, including lower haemoglobin levels and higher IgM levels deserve intensive monitoring, and aggressive therapy to reduce proteinuria should be carried out in pregnant IgAN patients with APO.

3.
J Pharmacol Toxicol Methods ; 129: 107551, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39245416

RESUMEN

This paper introduces an efficient methodology for conducting rat anesthesia experiments, aimed at enhancing the quality of raw brain signals obtained. The proposed approach enables the acquisition of animal brain signals during experiments without the confounding influence of muscle noise. Initially, the use of alpha-chloralose (a-c) in conjunction with Isoflurane is introduced to induce anesthesia in rats. Subsequently, Dexdomitor is administered to prevent muscular movements during the collection of brain signals, further refining the signal quality. Experimental outcomes conclusively demonstrate that our anesthesia method produces cleaner raw signals and exhibits improved robustness during data acquisition, outperforming existing methods that rely solely on Isoflurane or the Ketamine-Xylazine combination. Notably, this improved performance is achieved with minimal alterations to vital physiological parameters, including body temperature, respiration, and heart rates. Moreover, the efficacy of a-c in maintaining anesthesia for up to 7 h stands in contrast to the shorter durations achievable with continuous Isoflurane administration or the 30-min window offered by Ketamine-Xylazine, highlighting the practical advantages of our proposed method. Finally, post-experiment observations confirmed that the animals gradually returned to normal behavior without any signs of distress or adverse effects, indicating that our method was both effective and safe.

4.
Commun Chem ; 7(1): 206, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271821

RESUMEN

Although the pathogenesis of Alzheimer's disease (AD) is still unknown, the molecular pathological phenomena is clear, mainly due to mitochondrial dysfunction and central nervous system inflammation caused by imbalanced antioxidant capacity and synaptic dysfunction, so antioxidant therapy is still the preferred treatment for AD. However, although antioxidant enzymes have high catalytic efficiency, the substrate spectrum is narrow; Antioxidants have wider range of effects, but their efficiency is low. Since the antioxidant defense system in high-grade organisms is composed of both enzymatic and non-enzymatic systems, therefore we synthesized a metal-organic framework (MOF) with superoxide dismutase activity, and depending on the interface potential effect, curcumin was loaded to construct a synergistic antioxidant treatment system. More importantly, due to the complementary surface electrostatic potential between MOF and curcumin, the system exhibited both good antioxidant activity and efficient ß-amyloid plaque scavenging ability, which slowed down the cognitive dysfunction in the brain of AD mice.

5.
Sci Total Environ ; : 176242, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39277010

RESUMEN

Scholars usually unconsciously employ the Tapio decoupling model with a static perspective and results-oriented philosophy, which often leads to errors. Therefore, we propose an improved Tapio decoupling model that adopts a dynamic perspective and process-oriented philosophy. Taking China, the world's largest carbon emitter, as a case study, we investigate the decoupling of its provincial industrial carbon emissions (ICE) from industrial value-added (IVA) during 2005-2020 using both the conventional and improved decoupling model, followed by a comparative analysis of their results. Our findings are as follows: (1) Both China's ICE and IVA exhibited a general upward trend during the study period, with non-linear annual ICE and IVA variations observed across all provinces. (2) Overall, China's provincial IVA increasingly decoupled from ICE, with some provinces achieving a strong decoupling state during 2015-2020; however, from the long-term perspective spanning the entire study period, most provinces remained in a weak decoupling state. (3) The conventional decoupling model tends to yield overly optimistic results in empirical study of China, with the decoupling indices during the periods of 2005-2010 and 2005-2020 determined by the conventional model even had significant statistical difference between those determined by the improved model. (4) To ensure equity, differentiated carbon reduction policies should be tailored to each province, considering factors such as absolute carbon emissions, short-term decoupling states, and long-term decoupling states. The improved Tapio decoupling model is proposed as a valuable framework for researchers engaged in related studies.

6.
J Org Chem ; 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39276183

RESUMEN

Flavin-dependent catalysts are widely applied to aerobic monooxygenation/oxidation reactions. In contrast, flavin-catalyzed aerobic dioxygenation reactions exhibit higher atomic economy but are less reported, not to mention the relevant mechanistic studies. Herein, a density functional theory study on flavin-catalyzed aerobic epoxidation-oxygenolysis of alkenyl thioesters was performed for the first time. Different from the previous mechanistic proposal, a pathway featuring two catalytic stages, monoanionic flavin-C(4a)-peroxide/oxide intermediates, and a reverse reaction sequence (epoxidation goes prior to oxygenolysis) was revealed. In comparison, the pathways involving dianionic flavin catalysts, monoanionic flavin-N(5)-(hydro)peroxide/C(10a)-peroxide, or neutral flavin-C(4a)-hydroperoxide/hydroxide/N(5)-oxide, and the pathways where oxygenolysis goes prior to epoxidation are less favored. Epoxidation goes through intramolecular substitution of the O-O bond of anionic flavin-C(4a)-peroxide by ß-carbon, while the resulting flavin-C(4a)-oxide accomplishes the oxygenolysis. Furthermore, two other reaction modes, i.e., concerted O-O cleavage/1,2-shift of α-substituents and dyotropic rearrangement were discovered for the decomposition of other anionic peroxides, and preliminary rules were summarized for understanding the chemoselectivity for this process. This study sheds light on the different reaction features of numerous flavin-dioxygen derivatives, providing deeper insights into flavin-catalyzed dioxygenation reactions, and is expected to inspire experimental design based on unconventional anionic peroxides.

7.
Front Psychol ; 15: 1424223, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39282673

RESUMEN

Background: The aim of the present study was to investigate the intrinsic relationship between cultural values and social network index among college students. In addition, the present study explored the mediating role of self-monitoring in the relationship between horizontal collectivism cultural values and social network index, as well as the moderating role of self-efficacy, to provide a theoretical approach based on the intrinsic mechanism for college students to establish a good social network. Methods: A simple random cluster sampling method was used to investigate 376 college students with cultural values scale, self-monitoring scale, self-efficacy scale, and social network index scale, structural equation model was constructed using M-plus and SPSS. Results: The result indicated that individual horizontal collectivist cultural values positively predict social network index (ß = 0.477). Self-monitoring plays an intermediary role between cultural values and social network index, and self-efficacy plays a moderating role between self-monitoring and social network index. Conclusion: The level of an individual's social network activity is affected by the cultural values of horizontal collectivism and self-monitoring. Improving individual self-monitoring ability and self-efficacy can effectively improve the interpersonal relationships of college students.

8.
Nature ; 633(8030): 575-581, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39232169

RESUMEN

Futuristic technologies such as morphing aircrafts and super-strong artificial muscles depend on metal alloys being as strong as ultrahigh-strength steel yet as flexible as a polymer1-3. However, achieving such 'strong yet flexible' alloys has proven challenging4-9 because of the inevitable trade-off between strength and flexibility5,8,10. Here we report a Ti-50.8 at.% Ni strain glass alloy showing a combination of ultrahigh yield strength of σy ≈ 1.8 GPa and polymer-like ultralow elastic modulus of E ≈ 10.5 GPa, together with super-large rubber-like elastic strain of approximately 8%. As a result, it possesses a high flexibility figure of merit of σy/E ≈ 0.17 compared with existing structural materials. In addition, it can maintain such properties over a wide temperature range of -80 °C to +80 °C and demonstrates excellent fatigue resistance at high strain. The alloy was fabricated by a simple three-step thermomechanical treatment that is scalable to industrial lines, which leads not only to ultrahigh strength because of deformation strengthening, but also to ultralow modulus by the formation of a unique 'dual-seed strain glass' microstructure, composed of a strain glass matrix embedded with a small number of aligned R and B19' martensite 'seeds'. In situ X-ray diffractometry shows that the polymer-like deformation behaviour of the alloy originates from a nucleation-free reversible transition between strain glass and R and B19' martensite during loading and unloading. This exotic alloy with the potential for mass producibility may open a new horizon for many futuristic technologies, such as morphing aerospace vehicles, superman-type artificial muscles and artificial organs.


Asunto(s)
Aleaciones , Módulo de Elasticidad , Vidrio , Polímeros , Titanio , Aleaciones/química , Titanio/química , Polímeros/química , Vidrio/química , Níquel/química , Temperatura , Ensayo de Materiales , Estrés Mecánico
9.
Adv Mater ; : e2409877, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39279578

RESUMEN

Low-density magnesium (Mg) alloys are excellent engineering materials, and can significantly reduce energy consumption by replacing existing steel and aluminum materials. However, Mg species are susceptible to corrosion, especially in harsh environments (high-temperature or acidic), severely limiting the range of practical applications. Here, 2D covalent organic framework (COF) is synthesized with pore diameters ranging from 1.5 to 2.9 nm to obtain ultrafast nanofluidic channels. Loaded with silver (Ag+) ions, 2-mercaptobenzimidazole (2-MB) inhibitors are immobilized in the COF channels through the silver bridges. Based on the strong metal-complexing capability, Ag+ ions precipitated with various corrosive media (Cl-, Br-, I-, SO3 2-, S2-, S2O3 2- SO4 2-, CO3 2-, PO4 3-); meanwhile, the 2-MB inhibitors are rapidly released through the nanofluidic channels, forming a passivation film as a corrosion barrier to protect the Mg substrate. After integration with commercial polyethersulfone (PES), the COF-based coating exhibits high repairing capability achieving 100% damage restoration within 7 h, outperforming all existing coatings of Mg alloys. Notably, the coating shows almost complete protection of Mg alloys after being treated in respective 473 K, acidic (pH ≈4.0), and alkaline (pH ≈10.0) environments.

10.
Front Vet Sci ; 11: 1468615, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39280836

RESUMEN

Introduction: Altrenogest (ALT) is widely used to regulate the estrous cycle of sows and mares; however, currently used oral solutions of ALT are deficient in terms of dose accuracy and stability during use. To resolve these problems, we aimed to prepare softgel capsules of ALT with a unit dose equal to the clinically administered dose. Method: The shell of the softgel capsule was mainly composed of gelatin and glycerol, with titanium dioxide and red iron oxide as masking agents. Using the shake flask method, the contents were screened for ethyl acetate as a lipophilic solubilizing carrier based on soya bean oil. The contents were automatically filled and compressed into softgel capsules by a softgel capsule machine. The quality of the prepared softgel capsules was evaluated through a drug content test, an in vitro release test, and stability studies. Furthermore, bioequivalence studies were conducted with atrenogest oral solution. Results: The content is an ALT concentration of 2% oil solution and the specification of the softgel is 20 mg/capsule. In in vitro dissolution experiments, the softgel capsules were rapidly disintegrated and released in three different pH buffers, with a cumulative release rate of nearly 100% at 1 h. The softgel capsules were stable at high temperature and under strong light for 10 days, and the concentration of ALT was >99% in the 6-month accelerated and long-term tests. In the bioequivalence study, Tmax of the softgel capsules was 2.20 ± 0.77 h, t 1/2 was 6.36 ± 1.74 h, and C max was 64.65 ± 20.69 ng/ml. The main pharmacokinetic parameters T max, C max, AUC 0-t, and AUC 0-∞, did not differ significantly between the softgel capsules and the commercially available ALT oral solution (P > 0.05), and bioequivalence was demonstrated within the 90% confidence interval. Conclusion: The prepared softgel capsules have the advantages of higher content, ease of use with accurate dosing, good stability, and equivalence to ALT oral solution, implying that our softgels are ready for clinical use.

11.
J Am Chem Soc ; 146(33): 23566-23573, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39121013

RESUMEN

In the push to achieve net-zero emissions by 2050, nuclear power will play an essential role alongside renewable wind and solar power, and correspondingly global interest and investment in this well-established technology is accelerating. The uranium present in seawater could support nuclear power generation for centuries, but traditional adsorptive separation strategies have proven ineffective for the selective extraction of uranium from this vast resource. Here, we report the synthesis of nanowires of a triazine-linked two-dimensional covalent organic framework via a solvent modulation approach, which can be used to access nanowire external diameters ranging from 50 to 200 nm. The 100 nm nanowires are exceptionally promising for the capture of uranium(VI) via photocatalytic reduction. Under simulated sunlight and without the use of sacrificial agents, the nanowires achieve a uranium uptake of 10.9 g/g from a 100 ppm uranyl(VI) solution, which is the highest reported to date among materials studied for photo and electrocatalytic uranium capture. Significantly, these nanowires exhibit a uranium adsorption capacity of 34.5 mg/g after exposure to seawater under irradiation for 42 days, a record among all materials reported to date for uranium capture.

12.
EClinicalMedicine ; 74: 102707, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39105193

RESUMEN

Background: The long-term survival and perioperative outcomes of robotic-assisted lobectomy (RAL) and video-assisted lobectomy (VAL) in resectable non-small-cell lung cancer (NSCLC) were found to be comparable in retrospective studies, but they have not been investigated in a randomized trial setting. We conducted the RVlob trial to investigate if RAL was non-inferior to VAL in patients with resectable NSCLC. Methods: In this single-center, open-label, and parallel-arm randomized controlled trial conducted in Ruijin Hospital (Shanghai, China) between May 2017 and May 2020, we randomly assigned patients with resectable NSCLC in a 1:1 ratio to receive either RAL or VAL. One of the primary endpoints was 3-year overall survival. Secondary endpoints included 3-year disease-free survival. The Kaplan-Meier approach was used to calculate overall survival and disease-free survival at 3 years. This study was registered with ClinicalTrials.gov, NCT03134534. Findings: A total of 320 patients were randomized to receive RAL (n = 157) or VAL (n = 163). The baseline characteristics of patients were well balanced between the two groups. After a median follow-up of 58.0 months, the 3-year overall survival was 94.6% (95% confidence interval [CI], 91.0-98.3) in the RAL group and 91.5% (95% CI, 87.2-96.0) in the VAL group (hazard ratio [HR] for death, 0.65; 95% CI, 0.33-1.28; P = 0.21); noninferiority of RAL was confirmed according to the predefined margin of -5% (absolute difference, 2.96%; a one-sided 90% CI, -1.39% to ∞; P = 0.0029 for noninferiority). The 3-year disease-free survival was 88.7% (95% CI, 83.6-94.1) in the RAL group and 85.4% (95% CI, 80.0-91.2) in the VAL group (HR for disease recurrence or death, 0.87; 95% CI, 0.50-1.52; P = 0.62). Interpretation: This study is the first randomized trial to show that RAL resulted in non-inferior overall survival compared with VAL in patients with resectable NSCLC. Based on our results, RAL is an equally oncologically effective treatment and can be considered as an alternative to VAL for resectable NSCLC. Funding: National Natural Science Foundation of China (82072557), National Key Research and Development Program of China (2021YFC2500900), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20172005, the 2nd round of disbursement), program of Shanghai Academic Research Leader from Science and Technology Commission of Shanghai Municipality (20XD1402300), Novel Interdisciplinary Research Project from Shanghai Municipal Health Commission (2022JC023), and Interdisciplinary Program of Shanghai Jiao Tong University (YG2023ZD04).

13.
Biol Reprod ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39109839

RESUMEN

Mechanisms controlling trophoblast proliferation and differentiation during embryo implantation are poorly understood. Human trophoblast stem cells (TSC) and BMP4/A83-01/PD173074-treated pluripotent stem cell-derived trophoblast cells (BAP) are two widely employed, contemporary models to study trophoblast development and function, but how faithfully they mimic early trophoblast cells has not been fully examined. We evaluated the transcriptomes of trophoblast cells from BAP and TSC and directly compared them with those from peri-implantation human embryos during extended embryo culture (EEC) between embryonic day 8 to 12. The BAP and TSC grouped closely with trophoblast cells from EEC within each trophoblast sublineage following dimensional analysis and unsupervised hierarchical clustering. However, subtle differences in transcriptional programs existed within each trophoblast sublineage. We also validated the presence of six genes in peri-implantation human embryos by immunolocalization. Our analysis reveals that both BAP and TSC models have features of peri-implantation trophoblasts, while maintaining minor transcriptomic differences, and thus serve as valuable tools for studying implantation in lieu of human embryos.

14.
World J Gastroenterol ; 30(27): 3290-3303, 2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39086751

RESUMEN

BACKGROUND: The annual incidence of metabolic-associated fatty liver disease (MAFLD) in China has been increasing and is often overlooked owing to its insidious characteristics. Approximately 50% of the patients have a normal weight or are not obese. They are said to have lean-type MAFLD, and few studies of such patients are available. Because MAFLD is associated with abnormal lipid metabolism, lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis. AIM: To investigate the serum fatty-acid metabolic characteristics in lean-type MAFLD patients using targeted serum metabolomic technology. METHODS: Between January and June 2022, serum samples were collected from MAFLD patients and healthy individuals who were treated at Shanghai Putuo District Central Hospital for serum metabolomics analysis. Principal component analysis and orthogonal partial least squares-discriminant analysis models were developed, and univariate analysis was used to screen for biomarkers of lean-type MAFLD and analyze metabolic pathways. UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid (PA), oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) levels in lean-type MAFLD patients. RESULTS: Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.05). Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.01). The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals (P < 0.05) and the expression of triglycerides and fasting blood glucose were increased (P < 0.01). A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P < 0.05 and variable importance in projection > 1". The levels of PA, OA, LA, and AA were significantly increased compared with healthy individuals. CONCLUSION: The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly, yielding 65 identified biomarkers. PA, OA, LA, and AA exhibited the most significant changes, offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.


Asunto(s)
Biomarcadores , Ácidos Grasos , Metabolómica , Enfermedad del Hígado Graso no Alcohólico , Humanos , Metabolómica/métodos , Masculino , Femenino , Persona de Mediana Edad , Ácidos Grasos/sangre , Ácidos Grasos/metabolismo , Biomarcadores/sangre , Adulto , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , China/epidemiología , Metabolismo de los Lípidos , Estudios de Casos y Controles , Delgadez/sangre , Delgadez/diagnóstico
15.
CNS Neurosci Ther ; 30(8): e14885, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39129397

RESUMEN

BACKGROUND: Alzheimer's disease (AD) pathogenesis is complex. The pathophysiology is not fully understood, and safe and effective treatments are needed. Glycogen synthase kinase 3ß (GSK-3ß) mediates AD progression through several signaling pathways. Recently, several studies have found that various natural compounds from herbs and nutraceuticals can significantly improve AD symptoms. AIMS: This review aims to provide a comprehensive summary of the potential neuroprotective impacts of natural compounds as inhibitors of GSK-3ß in the treatment of AD. MATERIALS AND METHODS: We conducted a systematic literature search on PubMed, ScienceDirect, Web of Science, and Google Scholar, focusing on in vitro and in vivo studies that investigated natural compounds as inhibitors of GSK-3ß in the treatment of AD. RESULTS: The mechanism may be related to GSK-3ß activation inhibition to regulate amyloid beta production, tau protein hyperphosphorylation, cell apoptosis, and cellular inflammation. By reviewing recent studies on GSK-3ß inhibition in phytochemicals and AD intervention, flavonoids including oxyphylla A, quercetin, morin, icariin, linarin, genipin, and isoorientin were reported as potent GSK-3ß inhibitors for AD treatment. Polyphenols such as schisandrin B, magnolol, and dieckol have inhibitory effects on GSK-3ß in AD models, including in vivo models. Sulforaphene, ginsenoside Rd, gypenoside XVII, falcarindiol, epibrassinolides, 1,8-Cineole, and andrographolide are promising GSK-3ß inhibitors. CONCLUSIONS: Natural compounds from herbs and nutraceuticals are potential candidates for AD treatment. They may qualify as derivatives for development as promising compounds that provide enhanced pharmacological characteristics.


Asunto(s)
Enfermedad de Alzheimer , Suplementos Dietéticos , Glucógeno Sintasa Quinasa 3 beta , Enfermedad de Alzheimer/tratamiento farmacológico , Humanos , Animales , Glucógeno Sintasa Quinasa 3 beta/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico
16.
Inflamm Res ; 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39180691

RESUMEN

OBJECTIVE: Intestinal mucositis is one of the common side effects of anti-cancer chemotherapy. However, the molecular mechanisms involved in mucositis development remain incompletely understood. In this study, we investigated the function of receptor-interacting protein kinase 3 (RIP3/RIPK3) in regulating doxorubicin-induced intestinal mucositis and its potential mechanisms. METHODS: Intestinal mucositis animal models were induced in mice for in vivo studies. Rat intestinal cell line IEC-6 was used for in vitro studies. RNA­seq was used to explore the transcriptomic changes in doxorubicin-induced intestinal mucositis. Intact glycopeptide characterization using mass spectrometry was applied to identify α-1,2-fucosylated proteins associated with mucositis. RESULTS: Doxorubicin treatment increased RIP3 expression in the intestine and caused severe intestinal mucositis in the mice, depletion of RIP3 abolished doxorubicin-induced intestinal mucositis. RIP3-mediated doxorubicin-induced mucositis did not depend on mixed lineage kinase domain-like (MLKL) but on α-1,2-fucosyltransferase 2 (FUT2)-catalyzed α-1,2-fucosylation on inflammation-related proteins. Deficiency of MLKL did not affect intestinal mucositis, whereas inhibition of α-1,2-fucosylation by 2-deoxy-D-galactose (2dGal) profoundly attenuated doxorubicin-induced inflammation and mucositis. CONCLUSIONS: RIP3-FUT2 pathway is a central node in doxorubicin-induced intestinal mucositis. Targeting intestinal RIP3 and/or FUT2-mediated α-1,2-fucosylation may provide potential targets for preventing chemotherapy-induced intestinal mucositis.

17.
Artículo en Inglés | MEDLINE | ID: mdl-39178089

RESUMEN

Typical Convolutional Neural Networks (ConvNets) depend heavily on large amounts of image data and resort to an iterative optimization algorithm (e.g., SGD or Adam) to learn network parameters, making training very time- and resource-intensive. In this paper, we propose a new training paradigm and formulate the parameter learning of ConvNets into a prediction task: considering that there exist correlations between image datasets and their corresponding optimal network parameters of a given ConvNet, we explore if we can learn a hyper-mapping between them to capture the relations, such that we can directly predict the parameters of the network for an image dataset never seen during the training phase. To do this, we put forward a new hypernetwork-based model, called PudNet, which intends to learn a mapping between datasets and their corresponding network parameters, then predicts parameters for unseen data with only a single forward propagation. Moreover, our model benefits from a series of adaptive hyper-recurrent units sharing weights to capture the dependencies of parameters among different network layers. Extensive experiments demonstrate that our proposed method achieves good efficacy for unseen image datasets in two kinds of settings: Intra-dataset prediction and Inter-dataset prediction. Our PudNet can also well scale up to large-scale datasets, e.g., ImageNet-1K. It takes 8,967 GPU seconds to train ResNet-18 on the ImageNet-1K using GC from scratch and obtain a top-5 accuracy of 44.65%. However, our PudNet costs only 3.89 GPU seconds to predict the network parameters of ResNet-18 achieving comparable performance (44.92%), more than 2,300 times faster than the traditional training paradigm.

18.
Neuro Oncol ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39101440

RESUMEN

Neuroblastoma (NB), an heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations occurring during development contributing to NB. We discuss current treatment regimens, present and future directions for identification of novel therapeutic metabolic targets, differentiation agents, as well as personalized combinatory therapies as potential approaches for improving survival and quality of life of children with NB.

19.
J Org Chem ; 89(17): 12085-12093, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39180542

RESUMEN

A palladium-catalyzed domino cyclization/cycloisomerization reaction of alkyne-tethered carbamoyl chlorides with (E)-ß-chloroenones is reported. This reaction proceeds via a syn-carbopalladation of the alkyne, followed by a vinyl-PdII-catalyzed cycloisomerization of the (E)-ß-chloroenone cascade, which provides an efficient method to synthesize furan-linked methylene oxindoles. The reaction features stereodefined vinyl-PdII species, high to excellent 5-exo/6-endo selectivity, excellent Z/E selectivity, and the sequential formation of three bonds and bis-heterocycles. The strategy for the synthesis of furan-containing benzofurans has also been demonstrated.

20.
Medicine (Baltimore) ; 103(33): e39356, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39151535

RESUMEN

RATIONALE: Iliopsoas abscess is a rare acute medical condition. It usually occurs because of the spread of infection from adjacent structures and hematogenous spread. Clinical features include fever, backache, radiating nerve root pain, and leg weakness. When sepsis occurs, prompt recognition is required to initiate appropriate antimicrobial therapy and surgical drainage. PATIENT CONCERNS: A 65-year-old male presented to the outpatient department with a 2-day history of lower back, hip, and leg pain, for which analgesics were administered. During hospitalization, he experienced deterioration, becoming febrile, hypoxic, hypotensive, tachycardiac, and delirious. INTERVENTIONS: The patient was then intubated and ventilated. His family reported an additional history of acupuncture for back pain, which sustained an inflamed wound on his right forearm. Abdominal computed tomography was performed, which confirmed bilateral iliopsoas abscess without involvement of intra-abdominal organs. A preliminary report of blood culture revealed Gram-positive cocci. Echocardiography showed vegetation on the aortic valve, and moderate aortic regurgitation was sustained. He was started on vancomycin along with piperacillin-tazobactam. Ultrasound-guided percutaneous drainage was inserted into the bilateral abscess. Pus and blood yielded methicillin-sensitive Staphylococcus aureus. He remained septic. The repeat computed tomography showed the right abscess enlarged. A repeated echocardiogram showed that the vegetation increased. Further incision and surgical drainage were performed with continuous wash-out. OUTCOME: His condition improved after management and he was discharged to a regional hospital for ongoing care. CONCLUSION: Prompt diagnosis and surgical treatment are essential to improve patient outcomes. The unique aspect of this case is the persistence of the methicillin-sensitive Staphylococcus aureus infection. Centralized surgical services are pivotal in conjunction with robust antimicrobial regimens. LESSON: This case reinforces the importance of high clinical suspicion of an unknown source of sepsis.


Asunto(s)
Absceso del Psoas , Humanos , Masculino , Absceso del Psoas/terapia , Absceso del Psoas/diagnóstico , Absceso del Psoas/microbiología , Anciano , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/terapia , Infecciones Estafilocócicas/tratamiento farmacológico , Drenaje/métodos , Antibacterianos/uso terapéutico , Tomografía Computarizada por Rayos X
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