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1.
Light Sci Appl ; 13(1): 166, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39009583

RESUMEN

3-dB couplers, which are commonly used in photonic integrated circuits for on-chip information processing, precision measurement, and quantum computing, face challenges in achieving robust performance due to their limited 3-dB bandwidths and sensitivity to fabrication errors. To address this, we introduce topological physics to nanophotonics, developing a framework for topological 3-dB couplers. These couplers exhibit broad working wavelength range and robustness against fabrication dimensional errors. By leveraging valley-Hall topology and mirror symmetry, the photonic-crystal-slab couplers achieve ideal 3-dB splitting characterized by a wavelength-insensitive scattering matrix. Tolerance analysis confirms the superiority on broad bandwidth of 48 nm and robust splitting against dimensional errors of 20 nm. We further propose a topological interferometer for on-chip distance measurement, which also exhibits robustness against dimensional errors. This extension of topological principles to the fields of interferometers, may open up new possibilities for constructing robust wavelength division multiplexing, temperature-drift-insensitive sensing, and optical coherence tomography applications.

2.
Pharmacotherapy ; 44(7): 549-557, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38884415

RESUMEN

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.


Asunto(s)
Neoplasias Colorrectales , Tromboembolia Venosa , Humanos , Femenino , Masculino , Neoplasias Colorrectales/cirugía , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , China , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Factores de Riesgo , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Vías Clínicas , Guías de Práctica Clínica como Asunto
3.
Comput Med Imaging Graph ; 116: 102404, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38870599

RESUMEN

Magnetic Resonance Imaging (MRI) plays a pivotal role in the accurate measurement of brain subcortical structures in macaques, which is crucial for unraveling the complexities of brain structure and function, thereby enhancing our understanding of neurodegenerative diseases and brain development. However, due to significant differences in brain size, structure, and imaging characteristics between humans and macaques, computational tools developed for human neuroimaging studies often encounter obstacles when applied to macaques. In this context, we propose an Anatomy Attentional Fusion Network (AAF-Net), which integrates multimodal MRI data with anatomical constraints in a multi-scale framework to address the challenges posed by the dynamic development, regional heterogeneity, and age-related size variations of the juvenile macaque brain, thus achieving precise subcortical segmentation. Specifically, we generate a Signed Distance Map (SDM) based on the initial rough segmentation of the subcortical region by a network as an anatomical constraint, providing comprehensive information on positions, structures, and morphology. Then we construct AAF-Net to fully fuse the SDM anatomical constraints and multimodal images for refined segmentation. To thoroughly evaluate the performance of our proposed tool, over 700 macaque MRIs from 19 datasets were used in this study. Specifically, we employed two manually labeled longitudinal macaque datasets to develop the tool and complete four-fold cross-validations. Furthermore, we incorporated various external datasets to demonstrate the proposed tool's generalization capabilities and promise in brain development research. We have made this tool available as an open-source resource at https://github.com/TaoZhong11/Macaque_subcortical_segmentation for direct application.

4.
Front Endocrinol (Lausanne) ; 15: 1284283, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38919485

RESUMEN

Background: Clinically, the diagnosis and treatment of cholangiocarcinoma are generally different according to the location of occurrence, and the studies rarely consider the differences between different pathological types. Cholangiocarcinomas in large- and middle-sized intrahepatic bile ducts are mostly mucinous, while in small sized bile duct are not; mucinous extrahepatic cholangiocarcinomas are also more common than mucinous intrahepatic cholangiocarcinoma. However, it is unclear whether these pathological type differences are related to the prognosis. Methods: Data of total 22509 patients was analyzed from Surveillance, Epidemiology, and End Results program database out of which 22299 patients were diagnosed with common adeno cholangiocarcinoma while 210 were diagnosed with mucinous cholangiocarcinoma. Based on the propensity score matching (PSM) analysis, between these two groups' clinical, demographic, and therapeutic features were contrasted. The data were analyzed using Cox and LASSO regression analysis and Kaplan-Meier survival curves. Ultimately, overall survival (OS) and cancer specific survival (CSS) related prognostic models were established and validated in test and external datasets and nomograms were created to forecast these patients' prognosis. Results: There was no difference in prognosis between mucinous cholangiocarcinoma and adeno cholangiocarcinoma. Therefore, we constructed prognostic model and nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time. By comparing the 9 independent key characteristics i.e. Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy, risk scores were calculated for each individual. By integrating these two pathological types in OS and CSS prognostic models, effective prognosis prediction results could be achieved in multiple datasets (OS: AUC 0.70-0.87; CSS: AUC 0.74-0.89). Conclusion: Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy are the independent prognostic factors in OS or CSS of the patients with mucinous and ordinary cholangiocarcinoma. Nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time is of significance in clinical practice and management of cholangiocarcinoma.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Nomogramas , Humanos , Masculino , Colangiocarcinoma/terapia , Colangiocarcinoma/patología , Colangiocarcinoma/mortalidad , Femenino , Pronóstico , Persona de Mediana Edad , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/mortalidad , Estudios Retrospectivos , Anciano , Programa de VERF , Adulto
5.
Artículo en Inglés | MEDLINE | ID: mdl-38904633

RESUMEN

Objective: To study the clinical effectiveness of the 4P nursing model combined with Amisulpride and Clozapine in the management of psychiatric patients. Method: 100 patients with refractory schizophrenia treated in the Psychiatry department of Ganzhou People's Hospital from January 3, 2021, to January 4, 2022, were selected as the study subjects. They were randomly divided into observation and control groups, with 50 patients in each group. The clinical efficacy in the two groups was then assessed and compared using such parameters as the PANSS score, body mass index (BMI), blood lipid levels, incidence of side effects, and nursing satisfaction scores. Results: The difference in total treatment efficacy was statistically significant (χ2=11.724, 9.458, P ≤ .001, RR0.24, 95%CI (0.117-0.363)). The post-treatment PANSS score, positive symptom score, negative symptom score, and general pathological score treatment were all lower than the pre-treatment scores in both groups. The difference was statistically significant (RR0.12, 95%CI (0.098-0.203)). There was a reduction in the BMI of patients in the observation group after treatment, while there was an increase in that of patients in the control group. However, after treatment, there were significant reductions in the concentrations of T-CHO, LDL-C, and HDL-C in both groups (all P < .05, RR0.26, 95%CI (0.156-0.371)), with more significant reductions seen in the observation group than in the control group. The patients in the observation group recorded a much lower incidence of such side effects as drowsiness, nausea and vomiting, constipation, and weight gain and were more satisfied with the nursing they received as compared to their counterparts in the control group (all P < .05, RR0.28, 95%CI (0.171-0.351)). Conclusion: The 4P nursing model combined with Amisulpride and Clozapine can improve adherence to treatment, as well as the overall effectiveness of treatment. This nursing method has a high safety profile, improves the quality of life, and its use deserves more widespread promotion.

6.
Food Res Int ; 189: 114551, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38876590

RESUMEN

During the cold chain storage process, changes in metabolites and microorganisms are highly likely to lead to changes in meat quality. To elucidate the changes in the composition of metabolites and microbiota during cold chain storage of mutton, this study utilized untargeted metabolome and 5R 16S rRNA sequencing analyses to investigate the changes in the longissimus dorsi under different cold chain temperatures (4 °C and -20 °C). With the extension of cold chain storage time, the meat color darkened and the content of C18:2n-6, C20:3n-6, and C23:0 were significantly increased in mutton. In this study, nine metabolites, including 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine, alanylphenylala-nine, indole-3-acrylic acid and the others, were significantly altered during cold chain storage. The abundance of the dominant microorganisms, including Brachymonas, Aeromonas, Corynebacterium and Steroidobacter, was significantly altered. Furthermore, a high correlation was observed between the different metabolites and microorganisms. These findings provide an in-depth understanding of the effects of different cold chain storage temperatures and times on the quality of mutton.


Asunto(s)
Frío , Almacenamiento de Alimentos , Almacenamiento de Alimentos/métodos , Animales , Carne/microbiología , ARN Ribosómico 16S/genética , Bacterias/genética , Bacterias/clasificación , Bacterias/metabolismo , Microbiología de Alimentos , Microbiota , Metaboloma , Refrigeración
7.
Adv Sci (Weinh) ; : e2309004, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874509

RESUMEN

The current-generation adenine base editor (ABE) ABE8e, which has evolved from the prokaryotic evolution system, exhibits high efficiency in mediating A-to-G conversion and is presumed to be promising for gene therapy. However, its much wider editing window and substantially higher off-target editing activity restricted its applications in precise base editing for therapeutic use. This study uses a library-assisted protein evolution approach using eukaryotic cells to generate ABE variants with improved specificity and reduced off-target editing while maintaining high activity in human cells. The study generated an expanded set of ABEs with efficient editing activities and chose four evolved variants that offered either similar or modestly higher efficiency within a narrower editing window of protospacer position ≈4-7 compared to that of ABE8e in human cells, which would enable minimized bystander editing. Moreover, these variants resulted in reduced off-target editing events when delivered as plasmid or mRNA into human cells. Finally, these variants can install both disease-suppressing mutations and disease-correcting mutations efficiently with minimal undesired bystander editing making them promising approaches for specific therapeutic edits. In summary, the work establishes a mutant-library-assisted protein evolution method in eukaryotic cells and generates alternative ABE variants as efficient tools for precise human genome editing.

8.
BMC Genomics ; 25(1): 480, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750582

RESUMEN

Hu sheep (HS), a breed of sheep carrying the FecB mutation gene, is known for its "year-round estrus and multiple births" and is an ideal model for studying the high fecundity mechanisms of livestock. Through analyzing and comparing the genomic selection features of Hu sheep and other sheep breeds, we identified a series of candidate genes that may play a role in Hu sheep's high fecundity mechanisms. In this study, we conducted whole-genome resequencing on six breeds and screened key mutations significantly correlated with high reproductive traits in sheep. Notably, the CC2D1B gene was selected by the fixation index (FST) and the cross-population composite likelihood ratio (XP-CLR) methods in HS and other five breeds. It was worth noting that the CC2D1B gene in HS was different from that in other sheep breeds, and seven missense mutations have been identified. Furthermore, the linkage disequilibrium (LD) analysis revealed a strong linkage disequilibrium in this specific gene region. Subsequently, by performing different grouping based on FecB genotypes in Hu sheep, genome-wide selective signal analysis screened several genes related to reproduction, such as BMPR1B and PPM1K. Besides, FST analysis identified functional genes related to reproductive traits, including RHEB, HSPA2, PPP1CC, HVCN1, and CCDC63. Additionally, a missense mutation was found in the CCDC63 gene and the haplotype was different between the high reproduction (HR) group and low reproduction (LR) group in HS. In summary, we discovered genetic differentiation among six distinct breeding sheep breeds at the whole genome level. Additionally, we identified a set of genes which were associated with reproductive performance in Hu sheep and visualized how these genes differed in different breeds. These findings laid a theoretical foundation for understanding genetic mechanisms behind high prolific traits in sheep.


Asunto(s)
Tamaño de la Camada , Secuenciación Completa del Genoma , Animales , Tamaño de la Camada/genética , Ovinos/genética , Selección Genética , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple , Cruzamiento , Femenino , Fertilidad/genética , Reproducción/genética
9.
Cancer Lett ; 593: 216930, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38705566

RESUMEN

Radiotherapy (RT) in non-small cell lung cancer (NSCLC) triggers cellular senescence, complicating tumor microenvironments and affecting treatment outcomes. This study examines the role of lymphocyte immunoglobulin-like receptor B2 (LILRB2) in modulating RT-induced senescence and radiosensitivity in NSCLC. Through methodologies including irradiation, lentivirus transfection, and various molecular assays, we assessed LILRB2's expression and its impact on cellular senescence levels and tumor cell behaviors. Our findings reveal that RT upregulates LILRB2, facilitating senescence and a senescence-associated secretory phenotype (SASP), which in turn enhances tumor proliferation and resistance to radiation. Importantly, LILRB2 silencing attenuates these effects by inhibiting the JAK2/STAT3 pathway, significantly increasing radiosensitivity in NSCLC models. Clinical data correlate high LILRB2 expression with reduced RT response and poorer prognosis, suggesting LILRB2's pivotal role in RT-induced senescence and its potential as a therapeutic target to improve NSCLC radiosensitivity.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Senescencia Celular , Neoplasias Pulmonares , Tolerancia a Radiación , Receptores Inmunológicos , Humanos , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Senescencia Celular/efectos de la radiación , Tolerancia a Radiación/genética , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Animales , Janus Quinasa 2/metabolismo , Janus Quinasa 2/genética , Ratones , Transducción de Señal , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Fenotipo Secretor Asociado a la Senescencia/genética , Células A549 , Femenino
10.
Neuroimage ; 295: 120652, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38797384

RESUMEN

Accurate processing and analysis of non-human primate (NHP) brain magnetic resonance imaging (MRI) serves an indispensable role in understanding brain evolution, development, aging, and diseases. Despite the accumulation of diverse NHP brain MRI datasets at various developmental stages and from various imaging sites/scanners, existing computational tools designed for human MRI typically perform poor on NHP data, due to huge differences in brain sizes, morphologies, and imaging appearances across species, sites, and ages, highlighting the imperative for NHP-specialized MRI processing tools. To address this issue, in this paper, we present a robust, generic, and fully automated computational pipeline, called non-human primates Brain Extraction and Segmentation Toolbox (nBEST), whose main functionality includes brain extraction, non-cerebrum removal, and tissue segmentation. Building on cutting-edge deep learning techniques by employing lifelong learning to flexibly integrate data from diverse NHP populations and innovatively constructing 3D U-NeXt architecture, nBEST can well handle structural NHP brain MR images from multi-species, multi-site, and multi-developmental-stage (from neonates to the elderly). We extensively validated nBEST based on, to our knowledge, the largest assemblage dataset in NHP brain studies, encompassing 1,469 scans with 11 species (e.g., rhesus macaques, cynomolgus macaques, chimpanzees, marmosets, squirrel monkeys, etc.) from 23 independent datasets. Compared to alternative tools, nBEST outperforms in precision, applicability, robustness, comprehensiveness, and generalizability, greatly benefiting downstream longitudinal, cross-sectional, and cross-species quantitative analyses. We have made nBEST an open-source toolbox (https://github.com/TaoZhong11/nBEST) and we are committed to its continual refinement through lifelong learning with incoming data to greatly contribute to the research field.


Asunto(s)
Encéfalo , Aprendizaje Profundo , Imagen por Resonancia Magnética , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/anatomía & histología , Imagen por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Macaca mulatta , Neuroimagen/métodos , Pan troglodytes/anatomía & histología , Envejecimiento/fisiología
11.
Front Plant Sci ; 15: 1386109, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38708391

RESUMEN

Compared to conventional irrigation and fertilization, the Water-fertilizer coupling can significantly enhance the efficiency of water and fertilizer utilization, thereby promoting crop growth and increasing yield. Targeting the challenges of poor crop growth, low yield, and inefficient water and fertilizer utilization in the arid region of northwest China under conventional irrigation and fertilization practices. Therefore, a two-year on-farm experiment in 2022 and 2023 was conducted to study the effects of water-fertilizer coupling regulation on pumpkin growth, yield, water consumption (ET), and water and fertilizer use efficiency. Simultaneously the comprehensive evaluation of multiple objectives was carried out using principal component analysis (PCA) methods, so as to propose an suitable water-fertilizer coupling regulation scheme for the region. The experiment was set up as a two-factor trial using water-fertilizer integration technology under three irrigation volume (W1 = 37.5 mm, W2 = 45.5 mm, W3 = 52.5mm) and three organic fertilizer application amounts (F1 = 3900-300 kg ha-1, F2 = 4800-450 kg·ha-1, F3 = 5700-600 kg·ha-1), with the traditional irrigation and fertilization scheme from local farmers as control treatments (CK). The results indicated that irrigation volume and organic fertilizer application significantly affected pumpkin growth, yield, and water and fertilizer use efficiency (P<0.05). Pumpkin yield increased with increasing irrigation volume. Increasing organic fertilizer levels within a certain range benefited pumpkin plant growth, dry matter accumulation, and yield, however, excessive application beyond a certain level had inhibited effects on those. The increased fertilizer application under the same irrigation volume enhanced the efficiency of water and fertilizer utilization. However excessive irrigation only resulted in inefficient water consumption, reducing the water and fertilizer use efficiency. The Comprehensive evaluation by PCA revealed that the F2W3 treatment outperformed all the others, effectively addressing the triple objectives of increasing production, improving efficiency, and promoting green production. Therefore, F2W3 (Irrigation volume: 52.5 mm; Fertilizer application amounts: 4800-450 kg/ha-1) as a water and fertilizer management scheme for efficient pumpkin production in the arid region of northwest China.

12.
Discov Oncol ; 15(1): 164, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744743

RESUMEN

BACKGROUND: Interventional therapy, in conjunction with tyrosine kinase inhibitors (TKIs), has shown promising outcomes for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). With the advent of immunotherapy, the combined use of immune checkpoint inhibitors (ICIs) has attracted great attention due to their potential effectiveness in advanced HCC. This study aims to compare the efficacy and safety of a triple therapy regimen (Interventional therapy, TKIs and ICIs, IT-TKI-ICI) with a dual therapy regimen (Interventional therapy and TKIs, IT-TKI) in the treatment of HCC and PVTT (HCC-PVTT). METHODS: A comprehensive search was carried out in PubMed, Web of Science, Embase, Scopus, and the Cochrane Library databases. Primary outcome measures were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included tumor response rate, adverse event incidence as well as downstaging surgery rate. Statistical analysis was conducted using Revman 5.4 software. RESULTS: The meta-analysis finally included 6 cohort studies. The triple therapy group demonstrated significantly prolonged OS and PFS compared to the dual therapy group. Meanwhile, the former exhibited significantly higher rates of objective response rate (ORR), disease control rate (DCR) and better downstaging effects with a higher salvage surgery rate without significantly increasing adverse events. CONCLUSION: In comparison to dual therapy, the triple therapy with interventional therapy, TKIs, and ICIs demonstrates superior efficacy and equivalent safety for HCC-PVTT.

13.
Nat Prod Res ; : 1-7, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38742433

RESUMEN

Two new bicyclic sesquiterpenes,Δ9-2, 5, 11-trihydroxyl-ß-cis-bergamotene (3) and Nigrohydroin A (4), together with ten known compounds (1, 2 and 5-12) were obtained from endophytic fungus Nigrospora sp. E121. The structures were elucidated on the basis of their 1D and 2D NMR spectra and mass spectrometric data. The possible biosynthetic pathway of compounds 1, 2, 3 and 4 in Nigrospora sp. E121were reported according to literature. The phytotoxic assay results indicated that the acetyl fragment in α-acetylorcinol may contribute to the phytotoxic activity of this compound.

14.
Nat Commun ; 15(1): 4317, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773086

RESUMEN

Transition-metal catalyzed allylic substitution reactions of alkenes are among the most efficient methods for synthesizing diene compounds, driven by the inherent preference for an inner-sphere mechanism. Here, we present a demonstration of an outer-sphere mechanism in Rh-catalyzed allylic substitution reaction of simple alkenes using gem-difluorinated cyclopropanes as allyl surrogates. This unconventional mechanism offers an opportunity for the fluorine recycling of gem-difluorinated cyclopropanes via C - F bond cleavage/reformation, ultimately delivering allylic carbofluorination products. The developed method tolerates a wide range of simple alkenes, providing access to secondary, tertiary fluorides and gem-difluorides with 100% atom economy. DFT calculations reveal that the C - C bond formation goes through an unusual outer-sphere nucleophilic substitution of the alkenes to the allyl-Rh species instead of migration insertion, and the generated carbon cation then forms the C - F bond with tetrafluoroborate as a fluoride shuttle.

15.
Front Pharmacol ; 15: 1288255, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38645554

RESUMEN

The curative effect of single therapy for advanced cholangiocarcinoma (CCA) is poor, thus investigating combined treatment strategies holds promise for improving prognosis. Surufatinib (SUR) is a novel multikinase inhibitor that has been confirmed to prolong survival of patients with advanced CCA. Photodynamic therapy (PDT) can also ablate advanced CCA and relieve biliary obstruction. In this study, we explored the anti-CCA effect of SUR combined with PDT, and explored the underlying mechanism. We found that SUR could effectively inhibit the abilities of proliferation, migration and metastasis in CCA cells (HUCCT-1, RBE). The ability of SUR to inhibit CCA was also confirmed by the HUCCT-1 cell xenograft model in Balb/c nude mice and CCA patient-derived organoids. SUR combined with PDT can significantly enhance the inhibitory effect on CCA, and can be alleviated by two ferroptosis inhibitors (Ferrostatin-1, Deferoxamine). By detecting the level of reactive oxygen species, lipid peroxides, malondialdehyde and glutathione, we further confirmed that SUR combined with PDT can inhibit CCA cells by inducing ferroptosis. Glutathione peroxidase 4 (GPX4) belongs to the glutathione peroxidase family and is mainly responsible for the metabolism of intracellular hydrogen peroxide. GPX4 inhibits ferroptosis by reducing cytotoxic lipid peroxides (L-OOH) to the corresponding alcohols (L-OH). Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a member of the long-chain fatty acid coenzyme a synthetase family and is mainly involved in the biosynthesis and catabolism of fatty acids. ACSL4 induces ferroptosis by promoting the accumulation of lipid peroxides. Both SUR and PDT can induce ferroptosis by promoting ACSL4 and inhibiting GPX4. The regulation effect is found to be more significant in combined treatment group. In conclusion, SUR combined with PDT exerted an anti-CCA effect by inducing ferroptosis. Combination therapy provides a new idea for the clinical treatment of CCA.

16.
PLoS One ; 19(4): e0299740, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38598457

RESUMEN

The excessive use of antibiotics has resulted in the contamination of the environment with antibiotic resistance genes (ARGs), posing a significant threat to public health. Wastewater treatment plants (WWTPs) are known to be reservoirs of ARGs and considered to be hotspots for horizontal gene transfer (HGT) between bacterial communities. However, most studies focused on the distribution and dissemination of ARGs in hospital and urban WWTPs, and little is known about their fate in industrial WWTPs. In this study, collected the 15 wastewater samples containing N,N-dimethylformamide (DMF) from five stages of the anaerobic anoxic aerobic (AAO) process in an industrial WWTPs. The findings revealed a stepwise decrease in DMF and chemical oxygen demand (COD) content with the progression of treatment. However, the number and abundances of ARGs increase in the effluents of biological treatments. Furthermore, the residues of DMF and the treatment process altered the structure of the bacterial community. The correlation analysis indicated that the shift in bacterial community structures might be the main driver for the dynamics change of ARGs. Interestingly, observed that the AAO process may acted as a microbial source and increased the total abundance of ARGs instead of attenuating it. Additionally, found that non-pathogenic bacteria had higher ARGs abundance than pathogenic bacteria in effluents. The study provides insights into the microbial community structure and the mechanisms that drive the variation in ARGs abundance in industrial WWTPs.


Asunto(s)
Antibacterianos , Microbiota , Antibacterianos/farmacología , Dimetilformamida , Genes Bacterianos , Farmacorresistencia Microbiana/genética , Bacterias/genética , Microbiota/genética , Proliferación Celular
17.
Proc Natl Acad Sci U S A ; 121(16): e2319119121, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38588435

RESUMEN

The advancement of atomically precise dinuclear heterogeneous catalysts holds great potential in achieving efficient catalytic ozonation performance and contributes to the understanding of synergy mechanisms during reaction conditions. Herein, we demonstrate a "ship-in-a-bottle and pyrolysis" strategy that utilizes Fe2(CO)9 dinuclear-cluster to precisely construct Fe2 site, consisting of two Fe1-N3 units connected by Fe-Fe bonds and firmly bonded to N-doped carbon. Systematic characterizations and theoretical modeling reveal that the Fe-Fe coordination motif markedly reduced the devotion of the antibonding state in the Fe-O bond because of the strong orbital coupling interaction of dual Fe d-d orbitals. This facilitates O-O covalent bond cleavage of O3 and enhances binding strength with reaction intermediates (atomic oxygen species; *O and *OO), thus boosting catalytic ozonation performance. As a result, Fe dinuclear site catalyst exhibits 100% ozonation efficiency for CH3SH elimination, outperforming commercial MnO2 catalysts by 1,200-fold. This research provides insights into the atomic-level structure-activity relationship of ozonation catalysts and extends the use of dinuclear catalysts in catalytic ozonation and beyond.

18.
Water Res ; 256: 121608, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38657310

RESUMEN

The application of ozone (O3) disinfection has been hindered by its low solubility in water and the formation of disinfection by-products (DBPs). In this study, capacitive disinfection is applied as a pre-treatment for O3 oxidation, in which manganese dioxide with a rambutan-like hollow spherical structure is used as the electrode to increase the charge density on the electrode surface. When a voltage is applied, the negative-charged microbes are attracted to the electrodes and killed by electrical interactions. The contact between microbes and capacitive electrodes leads to changes in cell permeability and burst of reactive oxygen species, thereby promoting the diffusion of O3 into the cells. After O3 penetrates the cell membrane, it can directly attack the cytoplasmic constituents, accelerating fatal and irreversible damage to pathogens. As a result, the performance of the capacitance-O3 process is proved better than the direct sum of the two individual process efficiencies. The design of capacitance-O3 system is beneficial to reduce the ozone dosage and DBPs with a broader inactivation spectrum, which is conducive to the application of ozone in primary water disinfection.


Asunto(s)
Desinfección , Compuestos de Manganeso , Óxidos , Ozono , Ozono/farmacología , Ozono/química , Óxidos/farmacología , Óxidos/química , Desinfección/métodos , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Membrana Celular/efectos de los fármacos , Purificación del Agua/métodos , Electrodos , Bacterias/efectos de los fármacos
19.
Angew Chem Int Ed Engl ; 63(22): e202403602, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38515395

RESUMEN

The use of gem-difluorinated cyclopropanes (gem-DFCPs) as fluoroallyl surrogates under transition-metal catalysis has drawn considerable attention recently but such reactions are restricted to producing achiral or racemic mono-fluoroalkenes. Herein, we report the first enantioselective allylation of indoles under rhodium catalysis with gem-DFCPs. This reaction shows exceptional branched regioselectivity towards rhodium catalysis with gem-DFCPs, which provides an efficient route to enantioenriched fluoroallylated indoles with wide substrate scope and good functional group tolerance.

20.
Genes (Basel) ; 15(3)2024 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-38540389

RESUMEN

ß-1,4-N-acetylgalactosamine transferase 2 (B4GALNT2) is a vital candidate gene that affects the growth traits in sheep. However, whether it has the same function in goats remains to be investigated further. This study selected 348 Nanjiang Yellow goats, screened all exons, and conserved non-coding regions of the B4GALNT2 gene for single-nucleotide polymorphisms (SNPs). Our results revealed the presence of a synonymous mutation, rs672215506, within the exon of the B4GALNT2 gene in the Nanjiang Yellow goat population. The mutation resulted in a decrease in the mRNA stability of the B4GALNT2 gene. The results of SNP detection of the conserved non-coding region of the B4GALNT2 gene showed five potential regulatory SNPs in the Nanjiang Yellow goat population. Except for rs66095343, the ~500 bp fragments of the other four SNPs (rs649127714, rs649573228, rs652899012, and rs639183528) significantly increased the luciferase activity both in goat skeletal muscle satellite cells (MuSCs) and 293T cells. The genetic diversity indexes indicated low or intermediate levels for all six SNPs analyzed, and the genotype frequencies were in Hardy-Weinberg equilibrium. Association analysis showed that rs660965343, rs649127714, and rs649573228 significantly correlate with growth traits in the later stage of growth and development of Nanjiang Yellow goats. The haplotype combinations of H2H3 and H2H2 had higher body weight and greater body size. Moreover, H2H2 haplotype combinations significantly correlated with the litter size of the Nanjiang Yellow goats. The results of our study demonstrate the potential role of the B4GALNT2 gene as a functional genetic marker in the breeding programs of Nanjiang Yellow goats.


Asunto(s)
Cabras , Polimorfismo de Nucleótido Simple , Embarazo , Femenino , Animales , Ovinos , Cabras/genética , Polimorfismo de Nucleótido Simple/genética , Genotipo , Haplotipos , Tamaño de la Camada/genética
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