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1.
J Colloid Interface Sci ; 677(Pt A): 108-119, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39083888

RESUMEN

MnSO4-modified biochar (Mn-BC) was synthesized to remove berberine hydrochloride (BH) from wastewater by utilizing tea waste as raw material and MnSO4 as modifier. Brunel Emmett Taylor (BET) analysis reveals that the specific surface area (SSA) and average pore size (Dave) of Mn-BC are 1.4 and 7 times higher than those of pristine biochar apart, attributing to the dissociation effect can promote the dispersion of MnSO4 in the pores of the biochar. Meanwhile, the doping of Mn not only introduces additional oxygen-containing functional groups (OCFGs), but also modulates the π electron density. Furthermore, Response surface method (RSM) analysis reveals that Mn-BC dosage has the most significant effect on BH removal, followed by BH concentration and pH value. Kinetic and isothermal studies reveal that the BH adsorption process of Mn-BC was mainly dominated by chemical and monolayer adsorption. Meanwhile, density functional theory (DFT) calculations confirm the contribution of Mn doping to the conjugation effect in the adsorption system. Originally proposed Mn-BC is one potentially propitious material to eliminate BH from wastewater, meanwhile this also provides a newfangled conception over the sustainable utilization of tea waste resources.


Asunto(s)
Berberina , Carbón Orgánico , Berberina/química , Carbón Orgánico/química , Adsorción , Contaminantes Químicos del Agua/química , Propiedades de Superficie , Manganeso/química , Aguas Residuales/química , Teoría Funcional de la Densidad , Tamaño de la Partícula , Compuestos de Manganeso/química , Cinética
2.
World J Clin Cases ; 12(29): 6266-6270, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39417056

RESUMEN

Fecal incontinence is a common symptom among patients with rectal prolapse. Pudendal nerve terminal motor latency (PNTML) testing can serve as a reference indicator for predicting the outcomes of rectal prolapse surgery, thereby assisting surgeons in formulating more appropriate surgical plans. The direct correlation between preoperative PNTML testing results and postoperative fecal incontinence in patients with rectal prolapse remains a contentious issue, necessitating further clarification. Thus, we analyze the existing publications from both clinical and statistical perspectives to comprehensively evaluate the accuracy of preoperative PNTML testing in rectal prolapse and provide some feasible statistical solutions.

3.
J Anim Sci Biotechnol ; 15(1): 138, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39385285

RESUMEN

BACKGROUND: Aflatoxin B1 (AFB1) is a prevalent contaminant in agricultural products, presenting significant risks to animal health. CotA laccase from Bacillus licheniformis has shown significant efficacy in degrading mycotoxins in vitro test. The efficacy of Bacillus CotA laccase in animals, however, remains to be confirmed. A 2 × 2 factorial design was used to investigate the effects of Bacillus CotA laccase level (0 or 1 U/kg), AFB1 challenge (challenged or unchallenged) and their interactions on ducks. The purpose of this study was to evaluate the efficacy of Bacillus CotA laccase in alleviating AFB1 toxicosis of ducks. RESULTS: Bacillus CotA laccase alleviated AFB1-induced declines in growth performance of ducks accompanied by improved average daily gain (ADG) and lower feed/gain ratio (F/G). Bacillus CotA laccase ameliorated AFB1-induced gut barrier dysfunctions and inflammation testified by increasing the jejunal villi height/crypt depth ratio (VH/CD) and the mRNA expression of tight junction protein 1 (TJP1) and zonula occluden-1 (ZO-1) as well as decreasing the expression of inflammation-related genes in the jejunum of ducks. Amino acid metabolome showed that Bacillus CotA laccase ameliorated AFB1-induced amino acid metabolism disorders evidenced by increasing the level of glutamic acid in serum and upregulating the expression of amino acid transport related genes in jejunum of ducks. Bacillus CotA laccase ameliorated AFB1-induced liver injury testified by suppressing oxidative stress, inhibiting apoptosis, and downregulating the expression of hepatic metabolic enzyme related genes of ducks. Moreover, Bacillus CotA laccase degraded AFB1 in digestive tract of ducks, resulting in the reduced absorption level of AFB1 across intestinal epithelium testified by the decreased level of AFB1-DNA adduct in the liver, and the reduced content of AFB1 residues in liver and feces of ducks. CONCLUSIONS: Bacillus CotA laccase effectively improved the growth performance, intestinal health, amino acid metabolism and hepatic aflatoxin metabolism of ducks fed AFB1 diets, highlighting its potential as an efficient and safe feed enzyme for AFB1 degradation in animal production.

4.
Acc Chem Res ; 57(20): 2985-3006, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39356824

RESUMEN

ConspectusAlkenes and alkynes are fundamental building blocks in organic synthesis due to their commercial availability, bench-stability, and easy preparation. Selective functionalization of alkenes and alkynes is a crucial step for the synthesis of value-added compounds. Precise control over these reactions allows efficient construction of complex molecules with new functionalities. In recent decades, second- and third-row precious transition metal catalysts (palladium, platinum, rhodium, ruthenium) have been pivotal in the development of metal-catalyzed synthetic methodology. These metals exhibit excellent catalytic activity and selectivity, enabling efficient synthesis of functionalized organic molecules. However, recovery and reuse of precious metals have long been a challenge in this field. In recent years, exploration of earth-abundant metal-catalyzed organic reactions has interested both academic and industrial researchers. The development of such catalytic systems offers a promising approach to overcome the limitations of precious metal catalysts. For example, manganese is the third most naturally abundant transition metal with minimal toxicity and excellent biocompatibility. It exhibits good catalytic activity in several organic reactions, including C-H bond functionalization, selective reduction, and radical reactions. This Account outlines our recent progress in dinuclear manganese catalysis for selective functionalization of alkenes and alkynes. We have established the elementary manganese(I)-catalysis in transmetalation with R-B(OH)2. This finding has enabled us to apply the catalyst for the selective 1,2-difunctionalization of structurally diverse alkenes and alkynes. Mechanistic studies suggest a double manganese center synergistic activation model, as superior to Mn(CO)5Br in some cases. In addition, we have developed a ligand-tuned metalloradical strategy of dinuclear manganese catalysts (Mn2(CO)10), bridging the gap between the organometallics and radical chemistry, highlighting the unique radical functionalization of alkenes. Interestingly, using the same starting materials, different ligands can deliver completely different products. Meanwhile, a cooperative catalysis strategy involving manganese and other catalysts (e.g., cobalt, iminium) has also been developed and is briefly discussed. For manganese/iminium synergistic catalysis, a new mechanism for migratory insertion and demetalization-isomerization in synergistic HOMO-LUMO activation was disclosed. This strategy expands the application of low-valent manganese catalysts for enantioselective C-C bond-forming reactions. New reaction discovery is outpacing mechanism studies for dinuclear manganese catalysis, and future studies with time-resolved spectroscopy will improve understanding of the mechanism. Based on these intriguing findings, the precise functionalization of alkenes and alkynes by dinuclear manganese catalysts will expedite a novel activation model to enable late-stage functionalization of complex molecules.

5.
J Org Chem ; 89(21): 15447-15458, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39411848

RESUMEN

A gold self-relay catalysis driving a double annulation cascade starting from soft electron-biased 1,2-di(o-aminoaryl)alkynes and aldehydes is reported, enabling regioselective access to produce a series of [5]azahelicenes depending on the substitution pattern in generally good yields under mild conditions. This protocol exploits and unifies the π- and σ-Lewis acid capability of gold catalysts, featuring high molecular convergence, broad substrate flexibility, and good functional group compatibility and regioselectivity.

6.
Plant Cell Environ ; 47(12): 5498-5510, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39222055

RESUMEN

Pentatricopeptide repeat (PPR) gene family constitutes one of the largest gene families in plants, which mainly participate in RNA editing and RNA splicing of organellar RNAs, thereby affecting the organellar development. Recently, some evidence elucidated the important roles of PPR proteins in the albino process of plant leaves. However, the functions of PPR genes in the woody mangrove species have not been investigated. In this study, using a typical true mangrove Kandelia obovata, we systematically identified 298 PPR genes and characterized their general features and physicochemical properties, including evolutionary relationships, the subcellular localization, PPR motif type, the number of introns and PPR motifs, and isoelectric point, and so forth. Furthermore, we combined genome-wide association studies (GWAS) and transcriptome analysis to identify the genetic architecture and potential PPR genes associated with propagule leaves colour variations of K. obovata. As a result, we prioritized 16 PPR genes related to the albino phenotype using different strategies, including differentially expressed genes analysis and genetic diversity analysis. Further analysis discovered two genes of interest, namely Maker00002998 (PLS-type) and Maker00003187 (P-type), which were differentially expressed genes and causal genes detected by GWAS analysis. Moreover, we successfully predicted downstream target chloroplast genes (rps14, rpoC1 and rpoC2) bound by Maker00002998 PPR proteins. The experimental verification of RNA editing sites of rps14, rpoC1, and rpoC2 in our previous study and the verification of interaction between Maker00002998 and rps14 transcript using in vitro RNA pull-down assays revealed that Maker00002998 PPR protein might be involved in the post-transcriptional process of chloroplast genes. Our result provides new insights into the roles of PPR genes in the albinism mechanism of K. obovata propagule leaves.


Asunto(s)
Estudio de Asociación del Genoma Completo , Hojas de la Planta , Proteínas de Plantas , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Familia de Multigenes , Edición de ARN/genética , Rhizophoraceae/genética , Rhizophoraceae/fisiología , Filogenia , Regulación de la Expresión Génica de las Plantas , Perfilación de la Expresión Génica , Genes de Plantas , Genoma de Planta , Multiómica
7.
J Nanobiotechnology ; 22(1): 583, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39304945

RESUMEN

Kidney diseases represent a diverse range of conditions that compromise renal function and structure which characterized by a progressive deterioration of kidney function, may ultimately necessitate dialysis or kidney transplantation as end-stage treatment options. This review explores the complex landscape of kidney diseases, highlighting the limitations of existing treatments and the pressing need for innovative strategies. The paper delves into the role of extracellular vesicles (EVs) as emerging biomarkers and therapeutic agents in the context of kidney pathophysiology. Urinary extracellular vesicles (uEVs), in particular, offer a non-invasive means of assessing renal injury and monitoring disease progression. Additionally, mesenchymal stem cell-derived EVs (MSC-EVs) are examined for their immunomodulatory and tissue repair capabilities, presenting a promising avenue for novel therapeutic interventions. And discusses the potential of engineering EVs to enhance their targeting and therapeutic efficacy. This paper systematically integrates the latest research findings and aims to provide a comprehensive overview of the role of EVs in kidney disease, providing cutting-edge insights into their potential as a diagnostic and therapeutic tool.


Asunto(s)
Biomarcadores , Vesículas Extracelulares , Enfermedades Renales , Células Madre Mesenquimatosas , Vesículas Extracelulares/metabolismo , Humanos , Enfermedades Renales/metabolismo , Animales , Células Madre Mesenquimatosas/metabolismo , Biomarcadores/metabolismo , Riñón/metabolismo
8.
J Hazard Mater ; 480: 135926, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39307018

RESUMEN

Cadmium (Cd) pollution poses a significant ecological risk to mangrove ecosystems. Trehalose has excellent potential to mitigate the adverse effects of heavy metals. Unfortunately, the mechanisms related to trehalose-mediated heavy metal tolerance in plants remain elusive. In the present study, we firstly found that Cd induced the accumulation of trehalose and the differential expression of trehalose biosynthesis genes in the roots of mangrove plant Avicennia marina. Then, we found that the application of exogenous trehalose could alleviate the negative effects of Cd on A. marina by phenotypic observation. In addition, photosynthetic parameters and cellular ultrastructure analyses demonstrated that exogenous trehalose could improve the photosynthesis and stabilize the chloroplast and nuclear structure of the leaves of A. marina. Besides, exogenous trehalose could inhibit the Cd2+ influx from the root to reduce the Cd2+ content in A. marina. Subsequently, substrate sensitivity assay combined with ion uptake analysis using yeast cells showed that several trehalose biosynthesis genes may have a regulatory function for Cd2+ transport. Finally, we further identified a positive regulatory factor, AmTPS6, which enhances the Cd tolerance in transgenic Arabidopsis thaliana. Taken together, these findings provide new understanding to the mechanism of Cd tolerance in mangrove A. marina at trehalose aspect and a theoretical basis for the conservation of mangroves in coastal wetlands.

9.
Zhongguo Zhong Yao Za Zhi ; 49(15): 4139-4147, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39307746

RESUMEN

This study aims to explore the effect and mechanism of a mitochondrion-targeted derivative of ergosterol peroxide(Mito-EP) on breast cancer. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of MDA-MB-231 cells treated with different concentrations(0, 0.075, 0.15, 0.3, 0.6, 1.2, and 2.4 µmol·L~(-1)) of Mito-EP. Cells were grouped for treatment with water(blank control), low, medium, and high concentrations(0.15, 0.3, and 0.6 µmol·L~(-1)) of Mito-EP, and ergosterol peroxide(EP)(0.6 µmol·L~(-1)). After the cells were treated for 48 h, flow cytometry was employed to examine the apoptosis rate, reactive oxygen species(ROS) level, mitochondrial membrane potential, and cell cycle distribution, and the apoptosis, ROS, and mitochondrial membrane potential were observed by laser confocal microscopy. A mouse model bearing subcutaneous xenograft tumor was established by injecting 4T1 cell suspension and used to study the inhibitory effect of Mito-EP on breast cancer. Western blot was employed to determine the protein levels of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cytochrome C(Cyt C), cleaved caspase-7, and cleaved caspase-9 in cells and the tumor tissue. The results showed that Mito-EP reduced the proliferation rate of MDA-MB-231 cells in a concentration-dependent manner. Compared with the blank control group, EP(0.6 µmol·L~(-1)) caused slight changes in the apoptosis rate, ROS level, and mitochondrial membrane potential. However, Mito-EP increased the apoptosis rate, elevated the ROS level, decreased mitochondrial membrane potential, up-regulated the protein levels of Bax, Cyt C, cleaved caspase-7, and cleaved caspase-9, and down-regulated the protein level of Bcl-2(all P<0.05). Moreover, Mito-EP reduced the tumor volume and weight. In summary, Mito-EP may promote apoptosis in breast cancer cells by activating the mitochondrial apoptosis pathway.


Asunto(s)
Apoptosis , Neoplasias de la Mama , Ergosterol , Mitocondrias , Especies Reactivas de Oxígeno , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Femenino , Animales , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Apoptosis/efectos de los fármacos , Ratones , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Ergosterol/análogos & derivados , Ergosterol/farmacología , Proliferación Celular/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Antineoplásicos/química , Ratones Desnudos , Ciclo Celular/efectos de los fármacos
10.
Mol Cancer ; 23(1): 198, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39272149

RESUMEN

Tumor cells remodel the phenotype and function of tumor microenvironment (TME) cells to favor tumor progression. Previous studies have shown that neutrophils in TME are polarized to N2 tumor-associated neutrophils (TANs) by tumor derived factors, thus promoting tumor growth and metastasis, angiogenesis, therapy resistance, and immunosuppression. Exosomes act as critical intercellular messengers in human health and diseases including cancer. So far, the biological roles of exosomes from N2 TANs in gastric cancer have not been well characterized. Herein, we represented the first report that exosomes from N2 TANs promoted gastric cancer metastasis in vitro and in vivo. We found that exosomes from N2 TANs transferred miR-4745-5p/3911 to gastric cancer cells to downregulate SLIT2 (slit guidance ligand 2) gene expression. Adenovirus-mediated overexpression of SLIT2 reversed the promotion of gastric cancer metastasis by N2 TANs derived exosomes. We further revealed that gastric cancer cells induced glucose metabolic reprogramming in neutrophils through exosomal HMGB1 (high mobility group protein B1)/NF-κB pathway, which mediated neutrophil N2 polarization and miR-4745-5p/3911 upregulation. We further employed ddPCR (droplet digital PCR) to detect the expression of miR-4745-5p/3911 in N2 TANs exosomes from human serum samples and found their increased levels in gastric cancer patients compared to healthy controls and benign gastric disease patients. Conclusively, our results indicate that N2 TANs facilitate cancer metastasis via regulation of SLIT2 in gastric cancer cells by exosomal miR-4745-5p/3911, which provides a new insight into the roles of TME cells derived exosomes in gastric cancer metastasis and offers a potential biomarker for gastric cancer diagnosis.


Asunto(s)
Exosomas , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intercelular , MicroARNs , Proteínas del Tejido Nervioso , Neutrófilos , Neoplasias Gástricas , Microambiente Tumoral , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Exosomas/metabolismo , Exosomas/genética , Humanos , Neutrófilos/metabolismo , Neutrófilos/patología , MicroARNs/genética , Animales , Ratones , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Línea Celular Tumoral , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Microambiente Tumoral/genética , Metástasis de la Neoplasia , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Masculino
11.
J Diabetes Res ; 2024: 2552658, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39280993

RESUMEN

Background: Effective glycemic control is crucial for hospitalized patients, leading to benefits such as shorter hospital stays and reduced postoperative infection rates. While previous studies have emphasized the effectiveness of multidisciplinary collaborative stewardship for hospital-wide hyperglycemia management, patient perspectives and preferences have not been adequately considered. Objective: To identify factors influencing treatment preferences of Chinese hospitalized diabetes patients using discrete choice experiments (DCEs) and provide practical insights for the construction of a hospital-wide glycemic control programme. Methods: A face-to-face survey was conducted among diabetes patients admitted to nonendocrine departments in a tertiary hospital in Nanjing, China. The attributes and levels were determined based on DCE principles, and a conditional logit model was used to quantify patients' preferences. Results: A total of 157 respondents were analyzed. Antihyperglycemic effectiveness, healthcare providers, treatment regimen, monitoring frequency, and adverse reactions were the five attributes that significantly influenced patient preference (p < 0.05). Notably, an 80% glycemic control rate (ß = 2.009) and a multidisciplinary management team involving clinical pharmacists (ß = 1.346) had the greatest impact. Negative effects were observed for hypoglycemia (ß = -1.008), insulin pump use (ß = -0.746), and frequent glucose monitoring (ß = -0.523). Female patients exhibited higher concern for healthcare providers (ß = 1.172) compared to males. Younger and shorter-course patients prioritized antihyperglycemic effectiveness (ß = 3.330, ß = 1.510), while older patients preferred multidisciplinary management (ß = 1.186) and opposed increased monitoring frequency (ß = -0.703). Patients with higher educational backgrounds showed greater acceptance of continuous glucose monitoring (ß = 1.983), and those with higher annual income placed more emphasis on glycemic control rate. Conclusion: Treatment preferences of hospitalized diabetes patients are mainly influenced by antihyperglycemic effectiveness, adverse reactions, healthcare providers, and individual characteristics. Comprehensive consideration and an individualized therapy strategy should be given when constructing a hospital-wide glycemic control programme.


Asunto(s)
Glucemia , Diabetes Mellitus , Control Glucémico , Hospitalización , Hipoglucemiantes , Prioridad del Paciente , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Hipoglucemiantes/uso terapéutico , China , Diabetes Mellitus/terapia , Diabetes Mellitus/sangre , Glucemia/metabolismo , Adulto , Conducta de Elección , Encuestas y Cuestionarios , Hiperglucemia
12.
Crit Rev Oncol Hematol ; 204: 104514, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39332749

RESUMEN

Prostate cancer (PCa) is a prevalent malignant tumor affecting the male reproductive system and there are mainly three widely accepted PCa surgery types in current clinical treatment: open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP). Here, we aimed to evaluate the clinical effect of RARP for PCa patients compared with ORP and LRP based on the context of PCa encompass two dimensions: oncological outcomes (biochemical recurrence (BCR) and positive surgical margin (PSM)) and functional outcomes (urinary continence and recovery of erectile function) in this network meta-analysis (NMA). PubMed, Embase and Cochrane databases were systematically searched in January 7, 2024. 4 randomized controlled trials (RCTs) and 72 non-RCTs were included. RARP displayed significant positive effect on lower BCR and better recovery of erectile function but no significant differences existed among three surgery types for PSM and urinary continence.

13.
Cureus ; 16(7): e65301, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39184666

RESUMEN

Acute perimyocarditis is commonly preceded by viral illness and presents with non-specific complaints that can be a manifestation of serious cardiac complications such as arrhythmias and heart failure. While pericarditis is a known complication of thyrotoxicosis, termed "thyrotoxic pericarditis," concomitant new-onset perimyocarditis and Graves' disease, termed "thyro-pericarditis," has been reported. We present a case of thyro-pericarditis as the initial presentation of undiagnosed and untreated Graves' disease co-occurring with recent Coxsackievirus A and B infection. A 27-year-old male with a family history of undifferentiated hyperthyroidism presented with acute pleuritic chest pain and shortness of breath. Laboratory testing showed elevated cardiac troponin I with ST elevations and PR depressions on initial ECG. Left heart catheterization was normal, but transthoracic echocardiogram showed right ventricular systolic dysfunction and enlargement. Cardiac MRI demonstrated diffuse pericardial enhancement suggesting pericarditis. Thyroid function testing and thyroid ultrasound suggested auto-immune thyrotoxicosis. Serology noted abnormal Coxsackievirus A and B IgG antibody titers, suggesting prior infection. The patient was treated with colchicine, ibuprofen, methimazole, and metoprolol, with resolution of symptoms. Thyro-pericarditis is a rare concomitant presentation of both Graves' disease and myopericarditis, and it remains unknown whether there is an increased risk of adverse cardiac outcomes.

14.
Signal Transduct Target Ther ; 9(1): 215, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39134529

RESUMEN

Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Gefitinib , Indoles , Neoplasias Pulmonares , Mutación , Inhibidores de Proteínas Quinasas , Quinolinas , Humanos , Gefitinib/administración & dosificación , Gefitinib/efectos adversos , Gefitinib/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Quinolinas/uso terapéutico , Indoles/administración & dosificación , Indoles/uso terapéutico , Indoles/efectos adversos , Masculino , Femenino , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Persona de Mediana Edad , Anciano , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Anciano de 80 o más Años
15.
Neural Netw ; 179: 106479, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39146716

RESUMEN

Multi-Modal Entity Alignment (MMEA), aiming to discover matching entity pairs on two multi-modal knowledge graphs (MMKGs), is an essential task in knowledge graph fusion. Through mining feature information of MMKGs, entities are aligned to tackle the issue that an MMKG is incapable of effective integration. The recent attempt at neighbors and attribute fusion mainly focuses on aggregating multi-modal attributes, neglecting the structure effect with multi-modal attributes for entity alignment. This paper proposes an innovative approach, namely TriFac, to exploit embedding refinement for factorizing the original multi-modal knowledge graphs through a two-stage MMKG factorization. Notably, we propose triplet-aware graph neural networks to aggregate multi-relational features. We propose multi-modal fusion for aggregating multiple features and design three novel metrics to measure knowledge graph factorization performance on the unified factorized latent space. Empirical results indicate the effectiveness of TriFac, surpassing previous state-of-the-art models on two MMEA datasets and a power system dataset.


Asunto(s)
Algoritmos , Redes Neurales de la Computación , Minería de Datos/métodos , Humanos , Conocimiento
16.
Nature ; 633(8028): 216-223, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39143218

RESUMEN

Transthiolation (also known as transthioesterification) reactions are used in the biosynthesis of acetyl coenzyme A, fatty acids and polyketides, and for post-translational modification by ubiquitin (Ub) and ubiquitin-like (Ubl) proteins1-3. For the Ub pathway, E1 enzymes catalyse transthiolation from an E1~Ub thioester to an E2~Ub thioester. Transthiolation is also required for transfer of Ub from an E2~Ub thioester to HECT (homologous to E6AP C terminus) and RBR (ring-between-ring) E3 ligases to form E3~Ub thioesters4-6. How isoenergetic transfer of thioester bonds is driven forward by enzymes in the Ub pathway remains unclear. Here we isolate mimics of transient transthiolation intermediates for E1-Ub(T)-E2 and E2-Ub(T)-E3HECT complexes (where T denotes Ub in a thioester or Ub undergoing transthiolation) using a chemical strategy with native enzymes and near-native Ub to capture and visualize a continuum of structures determined by single-particle cryo-electron microscopy. These structures and accompanying biochemical experiments illuminate conformational changes in Ub, E1, E2 and E3 that are coordinated with the chemical reactions to facilitate directional transfer of Ub from each enzyme to the next.


Asunto(s)
Procesamiento Proteico-Postraduccional , Proteínas de Schizosaccharomyces pombe , Compuestos de Sulfhidrilo , Enzimas Activadoras de Ubiquitina , Enzimas Ubiquitina-Conjugadoras , Ubiquitina-Proteína Ligasas , Ubiquitina , Microscopía por Crioelectrón , Esterificación , Modelos Moleculares , Conformación Proteica , Schizosaccharomyces/enzimología , Schizosaccharomyces/ultraestructura , Proteínas de Schizosaccharomyces pombe/química , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/ultraestructura , Compuestos de Sulfhidrilo/química , Compuestos de Sulfhidrilo/metabolismo , Ubiquitina/química , Ubiquitina/metabolismo , Ubiquitina/ultraestructura , Enzimas Activadoras de Ubiquitina/química , Enzimas Activadoras de Ubiquitina/metabolismo , Enzimas Activadoras de Ubiquitina/ultraestructura , Enzimas Ubiquitina-Conjugadoras/química , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/ultraestructura , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/ultraestructura
17.
World J Clin Oncol ; 15(6): 667-673, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38946830

RESUMEN

Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death. Nanotherapies are able to selectively target the delivery of cancer therapeutics, thus improving overall antitumor efficiency and reducing conventional chemotherapy side effects. Mesoporous silica nanoparticles (MSNs) have attracted the attention of many researchers due to their remarkable advantages and biosafety. We offer insights into the recent advances of MSNs in CRC treatment and their potential clinical application value.

18.
Photoacoustics ; 38: 100631, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39055738

RESUMEN

We proposed a non-contact photoacoustic (PA) detection method using spectral domain optical coherence tomography (SDOCT). Two interference spectrums (A-lines) were acquired before and after the PA excitation with SDOCT. PA signal propagated within the sample causing the vibration. The vibration inner the sample introduced phase change between the acquired two A-lines. Thus, the PA signal can be detected by evaluating the difference in phase between the two A-lines. Based on the method, an OCT-PAM dual-mode imaging system was constructed. In the system, SDOCT served as the detection unit for PAM. Thus, the combination of the two imaging modalities was simplified. Another advantage of the system is that it realizes non-contact all-optic detection, which is attractive for biomedical imaging. Using the system, we imaged phantoms of carbon fibers, asparagus leaves and human hairs. Furthermore, the cortical vasculature of rat was imaged in vivo and the flow status was evaluated quantitatively.

19.
J Cardiothorac Surg ; 19(1): 406, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38951892

RESUMEN

OBJECTIVE: In this study, we compared the analgesic effects of intercostal nerve block (ICNB), ultrasound-guided paravertebral nerve block (PVB), and epidural block (EB) following single-port thoracoscopic lung surgery. METHOD: A total of 120 patients who underwent single-hole thoracoscopic lung surgery were randomly and equally divided into three groups: ICNB group, the PVB group, and the EB group. ICNB was performed under direct thoracoscopic visualization before the conclusion of the surgery in the ICNB group, while PVB and EB were performed after general anesthesia in the PVB and EB groups, respectively. Patient-controlled intravenous analgesia (PCIA) was used following the surgery in all the groups. The following indicators were recorded: Intraoperative sufentanil dosage, anesthesia awakening time, postoperative intubation time, nerve block operation time, postoperative visual analog scale (VAS) pain scores during resting and coughing at regular intervals of 0, 2, 4, 8, 24, and 48 h, the time until first PCIA, number of effective compressions within 24 h postoperatively, number of rescue analgesia interventions, and the side effects. RESULTS: In comparison to the ICNB group, the PVB and EB groups had a lower intraoperative sufentanil dosage, significantly shorter anesthesia awakening time, and postoperative intubation time, but longer nerve block operation time, lower VAS scores when resting and coughing within 24 h postoperatively (all p-values less than 0.05). Conversely, there were no statistically significant differences in VAS scores during resting and coughing after 24 h (all p-values greater than 0.05). Time to first PCIA, number of effective compressions and number of rescue analgesia at the 24-hour mark postoperatively were significantly better in the PVB and EB groups than that in the ICNB group (P < 0.05). However, there was a higher incidence of side effects observed in the EB group (P < 0.05). CONCLUSION: The analgesic effect of PVB and EB following single-port thoracoscopic lung surgery is better than that of ICNB. PVB causes fewer side effects and complications and is safer and more effective.


Asunto(s)
Nervios Intercostales , Bloqueo Nervioso , Dolor Postoperatorio , Ultrasonografía Intervencional , Humanos , Bloqueo Nervioso/métodos , Femenino , Masculino , Persona de Mediana Edad , Ultrasonografía Intervencional/métodos , Dolor Postoperatorio/prevención & control , Cirugía Torácica Asistida por Video/métodos , Anciano , Dimensión del Dolor , Adulto , Toracoscopía/métodos , Pulmón/cirugía
20.
Clin Kidney J ; 17(7): sfae157, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38979107

RESUMEN

Background: Previous research indicates that coronavirus disease 2019 (COVID-19) infection may have a role in triggering immunoglobulin A (IgA) nephropathy. However, limited research has explored the clinical implications of COVID-19 infection in individuals already diagnosed with IgA nephropathy. This study aimed to determine whether COVID-19 infection independently affects the subsequent trajectory of kidney function in IgA nephropathy patients. Methods: This was a single-center cohort study. The study included 199 patients diagnosed with IgA nephropathy. The COVID-19 infection status was determined using a combined method: a questionnaire and the Health Code application, both administered at the end of 2022 in northern China. Kidney function trajectory was assessed by the estimated glomerular filtration rate (eGFR), calculated based on serum creatinine levels measured during follow-up outpatient visits. The primary endpoint of interest was the eGFR trajectory. Results: Out of the 199 participants, 75% (n = 181) reported a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, determined through antigen or polymerase chain reaction tests, accounting for 79% (n = 143) of the infected patients. A significant majority (98%) experienced mild to moderate symptoms. Over a median follow-up period of 10.7 months post-COVID-19 infection, notable clinical events included gross hematuria in 30 patients (16.6%), which normalized within an average of 3 days. Additionally, a 2-fold increase in proteinuria or progression to the nephrotic range was observed in 10 individuals (5.5%). No cases of acute kidney injury were noted. COVID-19 exposure was associated with an absolute change in eGFR of 2.98 mL/min/1.73 m2 per month (95% confidence interval 0.46 to 5.50). However, in a fully adjusted model, the estimated changes in eGFR slope post-COVID-19 were -0.39 mL/min/1.73 m2 per month (95% confidence interval -0.83 to 0.06, P = .088) which included the possibility of no significant effect. Notably, a higher rate of kidney function decline was primarily observed in patients with a baseline eGFR <45 mL/min/1.73 m2 [-0.56 mL/min/1.73 m2 (-1.11 to -0.01), P = .048]. In the cohort, there were few instances of severe COVID-19 cases. The absence of long-term follow-up outcomes was observed. Conclusions: Overall, mild to moderate COVID-19 infection does not appear to significantly exacerbate the subsequent decline in kidney function among IgA nephropathy patients, particularly in those with preserved baseline kidney function.

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