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1.
Cell ; 182(1): 226-244.e17, 2020 07 09.
Artículo en Inglés | MEDLINE | ID: mdl-32649875

RESUMEN

Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.


Asunto(s)
Progresión de la Enfermedad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteogenómica , Fumar/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinógenos/toxicidad , Estudios de Cohortes , Citosina Desaminasa/metabolismo , Asia Oriental , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Genoma Humano , Humanos , Metaloproteinasas de la Matriz/metabolismo , Mutación/genética , Análisis de Componente Principal
2.
Proc Natl Acad Sci U S A ; 121(11): e2317702121, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38446850

RESUMEN

The electro-Fenton process is a state-of-the-art water treatment technology used to remove organic contaminants. However, the low O2 utilization efficiency (OUE, <1%) and high energy consumption remain the biggest obstacles to practical application. Here, we propose a local O2 concentrating (LOC) approach to increase the OUE by over 11-fold compared to the conventional simple O2 diffusion route. Due to the well-designed molecular structure, the LOC approach enables direct extraction of O2 from the bulk solution to the reaction interface; this eliminates the need to pump O2/air to overcome the sluggish O2 mass transfer and results in high Faradaic efficiencies (~50%) even under natural air diffusion conditions. Long-term operation of a flow-through pilot device indicated that the LOC approach saved more than 65% of the electric energy normally consumed in treating actual industrial wastewater, demonstrating the great potential of this system-level design to boost the electro-Fenton process for energy-efficient water remediation.

3.
J Am Chem Soc ; 146(12): 8500-8507, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38483183

RESUMEN

The selective transmembrane permeation of sodium ions achieved by biomimetic chemistry shows great potential to solve the problem of sodium ion transport blockade in diseases, but its implementation faces enormous difficulties. Herein, we design and synthesize a series of helically folded nanopores by employing a quinoline-oxadiazole structural sequence to finely replicate the pentahydrate structure of sodium ions. Surprisingly, these nanopores are capable of achieving sodium transmembrane permeation with ion selectivity at the level of natural sodium channels, as observed in rationally designed nanopores (M1-M5) with Na+/K+ ion selectivity ratio of up to 20.4. Moreover, slight structural variations in nanopore structures can switch ion transport modes between the channel and carrier. We found that, compared to the carrier mode, the channel mode not only transports ions faster but also has higher ion selectivity during transmembrane conduction, clearly illustrating that the trade-off phenomenon between ion selectivity and transport activity does not occur between the two transport modes of channel and carrier. At the same time, we also found that the spatial position and numbers of coordination sites are crucial for the sodium ion selectivity of the nanopores. Moreover, carrier M1 reported in this work is totally superior to the commercial Na+ carrier ETH2120, especially in terms of Na+/K+ ion selectivity, thus being a potentially practical Na+ carrier. Our study provides a new paradigm on the rational design of sodium-specific synthetic nanopores, which will open up the possibility for the application of artificial sodium-specific transmembrane permeation in biomedicine and disease treatment.

4.
Strahlenther Onkol ; 200(6): 535-543, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38453699

RESUMEN

PURPOSE: Vitexin can cooperate with hyperbaric oxygen to sensitize the radiotherapy of glioma by inhibiting the hypoxia-inducible factor (HIF)-1α. However, whether vitexin has a direct radiosensitization and how it affects the HIF-1α expression remain unclear. This study investigated these issues. METHODS: The SU3 cells-inoculated nude mice were divided into control, radiation, and vitexin + radiation groups. The vitexin + radiation-treated mice were intraperitoneally injected with 75 mg/kg vitexin daily for 21 days. On the 3rd, 10th, and 17th days during the vitexin treatment, the radiation-treated mice were locally irradiated with 10 Gy, respectively. In vitro, the microRNA (miR)-17-5p or miR-130b-3p mimics-transfected SU3 cells were used to examine the effects of vitexin plus radiation on expression of miR-17-5p- or miR-130b-3p-induced radioresistance-related pathway proteins. The effects of vitexin on miR-17-5p and miR-130b-3p expression in SU3 cells were also evaluated. RESULTS: Compared with the radiation group, the tumor volume, tumor weight, and expression of HIF-1α, vascular endothelial growth factor, and glucose transporter-1/3 proteins, miR-17-5p, and miR-130b-3p in tumor tissues in the vitexin + radiation group decreased, whereas the expression of phosphatase and tensin homolog (PTEN) protein increased. After treatment of miR-17-5p or miR-130b-3p mimics-transfected SU3 cells with vitexin plus radiation, the PTEN protein expression also increased, the HIF-1α protein expression decreased correspondingly. Moreover, vitexin decreased the miR-17-5p and miR-130b-3p expression in SU3 cells. CONCLUSION: Vitexin can enhance the radiosensitivity of glioma, and its mechanism may partly be related to the attenuation of HIF-1α pathway after lowering the inhibitory effect of miR-17-5p and miR-130b-3p on PTEN.


Asunto(s)
Apigenina , Glioma , Subunidad alfa del Factor 1 Inducible por Hipoxia , Ratones Desnudos , MicroARNs , Fosfohidrolasa PTEN , Tolerancia a Radiación , Animales , MicroARNs/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Apigenina/farmacología , Apigenina/uso terapéutico , Fosfohidrolasa PTEN/genética , Ratones , Glioma/radioterapia , Glioma/patología , Glioma/genética , Glioma/tratamiento farmacológico , Tolerancia a Radiación/efectos de los fármacos , Línea Celular Tumoral , Humanos , Transducción de Señal/efectos de los fármacos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamiento farmacológico , Fármacos Sensibilizantes a Radiaciones/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C
5.
Environ Sci Technol ; 58(15): 6793-6803, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38574343

RESUMEN

Current disinfection processes pose an emerging environmental risk due to the ineffective removal of antibiotic-resistant bacteria, especially disinfection residual bacteria (DRB) carrying multidrug-resistant plasmids (MRPs). However, the characteristics of DRB-carried MRPs are poorly understood. In this study, qPCR analysis reveals that the total absolute abundance of four plasmids in postdisinfection effluent decreases by 1.15 log units, while their relative abundance increases by 0.11 copies/cell compared to investigated wastewater treatment plant (WWTP) influent. We obtain three distinctive DRB-carried MRPs (pWWTP-01-03) from postdisinfection effluent, each carrying 9-11 antibiotic-resistant genes (ARGs). pWWTP-01 contains all 11 ARGs within an ∼25 Kbp chimeric genomic island showing strong patterns of recombination with MRPs from foodborne outbreaks and hospitals. Antibiotic-, disinfectant-, and heavy-metal-resistant genes on the same plasmid underscore the potential roles of disinfectants and heavy metals in the coselection of ARGs. Additionally, pWWTP-02 harbors an adhesin-type virulence operon, implying risks of both antibiotic resistance and pathogenicity upon entering environments. Furthermore, some MRPs from DRB are capable of transferring and could confer selective advantages to recipients under environmentally relevant antibiotic pressure. Overall, this study advances our understanding of DRB-carried MRPs and highlights the imminent need to monitor and control wastewater MRPs for environmental security.


Asunto(s)
Desinfectantes , Purificación del Agua , Desinfección , Genes Bacterianos , Bacterias/genética , Antibacterianos/farmacología , Desinfectantes/farmacología , Plásmidos/genética
6.
Acta Pharmacol Sin ; 45(1): 166-179, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37605050

RESUMEN

Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro. In this study, we evaluated the therapeutic potential of DZ2002 in rodent models of DED. SCOP-induced dry eye models were established in female rats and mice, while BAC-induced dry eye model was established in female rats. DZ2002 was administered as eye drops (0.25%, 1%) four times daily (20 µL per eye) for 7 or 14 consecutive days. We showed that topical application of DZ2002 concentration-dependently reduced corneal neovascularization and corneal opacity, as well as alleviated conjunctival irritation in both DED models. Furthermore, we observed that DZ2002 treatment decreased the expression of genes associated with angiogenesis and the levels of inflammation in the cornea and conjunctiva. Moreover, DZ2002 treatment in the BAC-induced DED model abolished the activation of the STAT3-PI3K-Akt-NF-κB pathways in corneal tissues. We also found that DZ2002 significantly inhibited the proliferation, migration, and tube formation of human umbilical endothelial cells (HUVECs) while downregulating the activation of the STAT3-PI3K-Akt-NF-κB pathway. These results suggest that DZ2002 exerts a therapeutic effect on corneal angiogenesis in DED, potentially by preventing the upregulation of the STAT3-PI3K-Akt-NF-κB pathways. Collectively, DZ2002 is a promising candidate for ophthalmic therapy, particularly in treating DED.


Asunto(s)
Neovascularización de la Córnea , Síndromes de Ojo Seco , Ratas , Humanos , Ratones , Animales , Femenino , Neovascularización de la Córnea/tratamiento farmacológico , Neovascularización de la Córnea/metabolismo , Neovascularización de la Córnea/patología , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Roedores/metabolismo , Células Endoteliales/metabolismo , Angiogénesis , Inflamación/tratamiento farmacológico , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/inducido químicamente , Factor de Transcripción STAT3/metabolismo
7.
Aging Clin Exp Res ; 36(1): 10, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38281223

RESUMEN

BACKGROUND: Circulating metabolites (CM) play a pivotal role in our overall health, yet the current evidence concerning the involvement of diverse CM in benign prostatic hyperplasia (BPH) remains limited. Mendelian randomization (MR) offers a promising avenue to explore the potential impact of CM on BPH. METHODS: In a forward MR analysis, a cohort of 249 circulating metabolites was employed as exposures to investigate their potential associations with BPH risk. Conversely, in a reverse MR analysis, BPH was employed as an exposure to assess its effects on CM. RESULTS: The forward MR analysis discerned a linkage between six metabolites and BPH, with careful consideration to excluding heterogeneity and pleiotropy. Subsequently, the reverse MR analysis unveiled that nine metabolic compounds, mainly comprising phospholipids and triglycerides, potentially exhibit elevated levels in BPH patients. CONCLUSION: Bidirectional MR analysis furnishes genetic insight into the interplay between CM and BPH. The prominence of lipids and triglycerides emerges as significant factors intricately linked to BPH risk.


Asunto(s)
Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/genética , Hiperplasia , Análisis de la Aleatorización Mendeliana , Próstata , Triglicéridos
8.
Angew Chem Int Ed Engl ; 63(29): e202404568, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38696242

RESUMEN

Few-atom metal clusters (FAMCs) exhibit superior performance in catalyzing complex molecular transformations due to their special spatial environments and electronic states, compared to single-atom catalysts (SACs). However, achieving the efficient and accurate synthesis of FAMCs while avoiding the formation of other species, such as nanoparticles and SACs, still remains challenges. Herein, we report a two-step strategy for synthesis of few-atom platinum (Pt) clusters by predeposition of zinc single-atom-glue (Zn1) on MgO nanosheets (Ptn-Zn1/MgO), where FAMCs can be obtained over a wide range of Pt contents (0.09 to 1.45 wt %). Zn atoms can act as Lewis acidic sites to allow electron transfer between Zn and Pt through bridging O atoms, which play a crucial role in the formation and stabilization of few-atom Pt clusters. Ptn-Zn1/MgO exhibited a high selectivity of 93 % for anti-Markovnikov alkene hydrosilylation. Moreover, an excellent activity with a turnover frequency of up to 1.6×104 h-1 can be achieved, exceeding most of the reported Pt SACs. Further theoretical studies revealed that the Pt atoms in Ptn-Zn1/MgO possess moderate steric hindrance, which enables high selectivity and activity for hydrosilylation. This work presents some guidelines for utilizing atomic-scale species to increase the synthesis efficiency and precision of FAMCs.

9.
Cancer ; 129(5): 790-802, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36537587

RESUMEN

BACKGROUND: This study analyzed data from two consecutive protocols for children newly diagnosed with acute lymphoblastic leukemia (ALL) to determine the clinical impact of minimal/measurable residual disease (MRD) and recently identified tumor genetic subtypes. METHODS: Genetic subtypes were determined by sequential approaches including DNA indexing, reverse transcriptase-polymerase chain reaction, multiplex ligation-dependent probe amplification, and RNA-sequencing. MRD was assessed by flow cytometry. The Taiwan Pediatric Oncology Group TPOG-ALL-2013 study enrolled patients who received MRD-directed therapy. RESULTS: The 5-year event-free survival (EFS) and overall survival rates in the 2013 cohort were 77.8% and 86.9% compared to those of the 2002 cohort, which were 62.4% and 76.5%. Among patients treated with MRD-guided therapy, those with ETV6-RUNX1 fusion and high hyperdiploidy had the highest 5-year EFS (91.4% and 89.6%, respectively). The addition of dasatinib improved outcomes in patients with BCR-ABL1 ALL. Recently identified subtypes like DUX4-rearranged, ZNF384-rearranged, MEF2D-rearranged, and PAX5alt subtypes were frequently positive for MRD after remission induction, and these patients consequently received intensified chemotherapy. Treatment intensification according to the MRD improved the outcomes of patients presenting DUX4 rearrangements. In high-risk or very-high-risk subtypes, the TPOG-ALL-2013 regimen did not confer significant improvements compared to TPOG-ALL-2002, and the outcomes of BCR-ABL1-like, MEF2D-rearranged, and KMT2A-rearranged ALL subtypes (in addition to those of T-cell ALL) were not sufficiently good. Novel agents or approaches are needed to improve the outcomes for these patients. CONCLUSIONS: The TPOG-ALL-2013 study yielded outcomes superior to those of patients treated in the preceding TPOG-ALL-2002 study. This study provides important data to inform the design of future clinical trials in Taiwan. PLAIN LANGUAGE SUMMARY: MRD-directed therapy improved the outcomes for pediatric ALL, especially standard-risk patients. Genomic analyses and MRD might be used together for risk-directed therapy of childhood ALL. Our work provides important data to inform the design of future clinical trials in Taiwan.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Neoplasia Residual/genética , Neoplasia Residual/diagnóstico , Pronóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Dasatinib/uso terapéutico , Inducción de Remisión
10.
J Med Virol ; 95(1): e28267, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36319439

RESUMEN

BACKGROUND: Myocardial injury is a major complication of sepsis and a key factor affecting prognosis. Therefore, early and accurate diagnosis and timely management of sepsis-induced cardiomyopathy (SICM) are of great significance for the prevention and treatment of sepsis. The gut microbiota has been shown to be closely associated with sepsis or myocardial injury, but the association between the gut microbiota and SICM is not fully understood. This study aimed to explore the link between gut microbiota composition and SICM. METHODS: A case-control and single-center study of clinical features and gut microbiota profiles by Metagenome and Virome was conducted in SICM patients (n = 15) and sepsis-uninduced cardiomyopathy patients (SNICM, n = 16). RESULTS: Compared with SNICM patients, SICM patients showed significant myocardial injury and higher 28-day mortality, SOFA scores, lactate levels, and infection levels on admission. Meanwhile, differences in the composition of gut bacteria, archaea, fungi, and viruses were analyzed between the two groups. Differential gut bacteria or viruses were found to have a good predictive effect on SICM. Furthermore, gut bacteria and viruses that differed between the two groups were strongly related. The abundance of Cronobacter and Cronobacter phage was higher in the SICM group than in the SNICM group, and the receiver operating characteristic curve showed that Cronobacter and Cronobacter phage both had a good predictive effect on SICM. CONCLUSIONS: SICM patients may have specific gut microbiota signatures, and Cronobacter and Cronobacter phages have a good ability to identify and diagnose SICM.


Asunto(s)
Bacteriófagos , Cardiomiopatías , Microbioma Gastrointestinal , Sepsis , Humanos , Estudios de Casos y Controles , Disbiosis/complicaciones , Cardiomiopatías/etiología , Bacterias/genética , Sepsis/complicaciones
11.
Mol Psychiatry ; 27(10): 4077-4091, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35804093

RESUMEN

Fear extinction allows for adaptive control of learned fear responses but often fails, resulting in a renewal or spontaneous recovery of the extinguished fear, i.e., forgetting of the extinction memory readily occurs. Using an activity-dependent neuronal labeling strategy, we demonstrate that engram neurons for fear extinction memory are dynamically positioned in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral hippocampus (vHPC), which constitute an engram construct in the term of directional engram synaptic connectivity from the BLA or vHPC to mPFC, but not that in the opposite direction, for retrieval of extinction memory. Fear renewal or spontaneous recovery switches the extinction engram construct from an accessible to inaccessible state, whereas additional extinction learning or optogenetic induction of long-term potentiation restores the directional engram connectivity and prevents the return of fear. Thus, the plasticity of engram construct underlies forgetting of extinction memory.


Asunto(s)
Complejo Nuclear Basolateral , Extinción Psicológica , Extinción Psicológica/fisiología , Miedo/fisiología , Corteza Prefrontal/fisiología , Condicionamiento Psicológico/fisiología , Complejo Nuclear Basolateral/fisiología
12.
Environ Sci Technol ; 57(26): 9744-9753, 2023 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-37339114

RESUMEN

Phthalate monoesters (me-PAEs) have been used as biomarkers for assessing human exposure to phthalate esters (PAEs) for a long time, and studies on the sources and distribution of me-PAEs in the environment are limited. In this study, dust samples from microenvironments were collected to measure the occurrence of PAEs and me-PAEs, as well as the bacterial diversity. The results indicated that me-PAEs coexisted with PAEs in different microenvironmental dust samples, with concentrations of nine PAEs and 16 me-PAEs ranging from 108 to 1450 µg/g (median range) and 6.00 to 21.6 µg/g, respectively. The concentrations of several low molecular weight me-PAEs (e.g., monomethyl phthalate and monoethyl phthalate) in dust were even significantly higher than those of their parents. The bacteria in the dust were mainly predominant with Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes (total abundance >90%). Bacteria from bus and air conditioning dust samples had the highest species richness and species diversity. Seven genes of suspected enzymes with the ability to degrade PAEs were selected, and the concentration of me-PAEs increased with increasing abundance of enzyme function. Our findings will provide useful information on the profiles of me-PAEs and their potential sources in indoor dusts, which will benefit the accurate estimation of human exposure.


Asunto(s)
Polvo , Ácidos Ftálicos , Humanos , Polvo/análisis , Ésteres/análisis , Ácidos Ftálicos/análisis , China
13.
BMC Pediatr ; 23(1): 359, 2023 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-37442946

RESUMEN

OBJECTIVE: To investigate the feasibility and clinical outcomes of early enteral nutrition (EN) in critically ill neonates supported by extracorporeal membrane oxygenation (ECMO). METHODS: We retrospectively analyzed the clinical data of 16 critically ill neonates who received ECMO support for respiratory and circulatory failure from July 2021 to December 2022 at our center. The patients were divided into two groups: the early EN group (< 24 h) and the late EN group (> 24 h). The related clinical and nutrition-related indicators between the groups were compared. RESULTS: There was a significant difference in the time from ECMO treatment to the start of EN between the early EN group (9 patients, 56.2%) and the late EN group (7 patients, 43.8%) (P < 0.05). However, there were no significant differences in ECMO duration, hospitalization time, vasoactive-inotropic score (VIS), intestinal oxygen saturation, or routine stool occult blood (OB) test between the two groups (all P > 0.05). The incidence of complications such as intestinal obstruction, abdominal distension, diarrhea, and necrotizing enterocolitis (NEC) was slightly lower in the early EN group, but the differences were not statistically significant (all P > 0.05). The early EN group had a shorter time [3.6 (3.5, 5) vs. 7.5 (5.9, 8.5) d] to reach full gastrointestinal nutrition compared to the late EN group (P < 0.05). CONCLUSION: Providing early nutritional support through enteral feeding to critically ill neonates receiving ECMO treatment is both safe and practical, but close monitoring of clinical and nutritional indicators is essential.


Asunto(s)
Nutrición Enteral , Oxigenación por Membrana Extracorpórea , Humanos , Recién Nacido , Enfermedad Crítica/terapia , Estudios Retrospectivos , Estado Nutricional
14.
J Environ Manage ; 347: 119092, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37742410

RESUMEN

The prevalence of antibiotic resistance genes (ARGs) in diverse habitats threatens public health. Watersheds represent critical freshwater ecosystems that interact with both the soil and atmosphere. However, a holistic understanding of ARGs distribution across these environmental media is currently inadequate. We profiled ARGs and bacterial communities in air-water-soil in the same watershed area during four seasons using high-throughput qPCR and 16S rRNA gene sequencing. Our findings demonstrated that aminoglycoside resistance genes (58.5%) were dominant in water, and multidrug resistance genes (55.2% and 54.2%) were dominant in soil and air. Five ARGs and nineteen bacterial genera were consistently detected in all samples, were named as shared genes or bacteria. Co-occurrence Network analysis revealed the co-occurrence module of resistance genes, mobile genetic elements (MGEs), and potential bacterial hosts, indicating that shared genes and bacteria may persist and co-spread across different environmental media. The risk assessment framework, based on ARGs' abundance, detection rate, and mobility, identified 33 high-risk ARGs. This is essential to evaluate the health risks of ARGs and to develop strategies to limit the threat of antibiotic resistance. Our study offers new insights into the risks associated with ARGs in the environment and suggests that ARGs may depend on specific bacterial cohabitants that co-exist with MGEs to facilitate their spread across environmental interfaces.


Asunto(s)
Agua Potable , Genes Bacterianos , Suelo , Antibacterianos/farmacología , Ecosistema , ARN Ribosómico 16S/genética , Farmacorresistencia Microbiana/genética , Bacterias/genética
15.
Zhongguo Zhong Yao Za Zhi ; 48(23): 6334-6346, 2023 Dec.
Artículo en Zh | MEDLINE | ID: mdl-38211990

RESUMEN

Artemisiae Argyi Folium is commonly used in clinical practice. Artemisiae Verlotori Folium, the dried leaves of Artemisia verlotorum, is often used as a folk substitute for Artemisiae Argyi Folium in Lingnan area. In this study, gas chromatography-triple quadrupole mass spectrometry(GC-MS) was used to detect the volatile oil components of 27 samples of Artemisiae Verlotori Folium and 13 samples of Artemisiae Argyi Folium, and the volatile components were compared between the two species. The internal standard method was combined with multi-reaction monitoring mode(MRM) to determine the content of six major volatile components. Hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were carried out for the content data. The results showed that the Artemisiae Argyi Folium samples had higher content and more abundant volatile oils than the Artemisiae Verlotori Folium samples. Artemisiae Argyi Folium mainly had the components with lower boiling points, while Artemisiae Verlotori Folium mainly had the components with higher boiling points. Terpenoids were the main volatile components in Artemisiae Verlotori Folium(mainly sesquiterpenoids) and Artemisiae Argyi Folium(monoterpenoids). In addition, Artemisiae Argyi Folium had higher content of oxygen-containing derivatives than Artemisiae Verlotori Folium. Furthermore, the stoichiometric analysis showed that the two species could be distinguished by both HCA and OPLS-DA, indicating that the volatile components of the two were significantly different. This study can provide a scientific basis for the quality evaluation and data support for the local rational application of Artemisiae Verlotori Folium in Lingnan.


Asunto(s)
Artemisia , Medicamentos Herbarios Chinos , Aceites Volátiles , Cromatografía de Gases y Espectrometría de Masas , Quimiometría , Hojas de la Planta
16.
Small ; 18(1): e2104229, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34791802

RESUMEN

The treatment of diabetic wounds remains a major challenge in clinical practice, with chronic wounds characterized by multiple drug-resistant bacterial infections, angiopathy, and oxidative damage to the microenvironment. Herein, a novel in situ injectable HA@MnO2 /FGF-2/Exos hydrogel is introduced for improving diabetic wound healing. Through a simple local injection, this hydrogel is able to form a protective barrier covering the wound, providing rapid hemostasis and long-term antibacterial protection. The MnO2 /ε-PL nanosheet is able to catalyze the excess H2 O2 produced in the wound, converting it to O2 , thus not only eliminating the harmful effects of H2 O2 but also providing O2 for wound healing. Moreover, the release of M2-derived Exosomes (M2 Exos) and FGF-2 growth factor stimulates angiogenesis and epithelization, respectively. These in vivo and in vitro results demonstrate accelerated healing of diabetic wounds with the use of the HA@MnO2 /FGF-2/Exos hydrogel, presenting a viable strategy for chronic diabetic wound repair.


Asunto(s)
Diabetes Mellitus , Exosomas , Exosomas/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Humanos , Hidrogeles , Compuestos de Manganeso , Estrés Oxidativo , Óxidos , Cicatrización de Heridas
17.
Cell Commun Signal ; 20(1): 165, 2022 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-36284303

RESUMEN

BACKGROUND: Postmenopausal bone loss, mainly caused by excessive bone resorption mediated by osteoclasts, has become a global public health burden. Metformin, a hypoglycemic drug, has been reported to have beneficial effects on maintaining bone health. However, the role and underlying mechanism of metformin in ovariectomized (OVX)-induced bone loss is still vague. RESULTS: In this study, we demonstrated for the first time that metformin administration alleviated bone loss in postmenopausal women and ovariectomized mice, based on reduced bone resorption markers, increased bone mineral density (BMD) and improvement of bone microstructure. Then, osteoclast precursors administered metformin in vitro and in vivo were collected to examine the differentiation potential and autophagical level. The mechanism was investigated by infection with lentivirus-mediated BNIP3 or E2F1 overexpression. We observed a dramatical inhibition of autophagosome synthesis and osteoclast formation and activity. Treatment with RAPA, an autophagy activator, abrogated the metformin-mediated autophagy downregulation and inhibition of osteoclastogenesis. Additionally, overexpression of E2F1 demonstrated that reduction of OVX-upregulated autophagy mediated by metformin was E2F1 dependent. Mechanistically, metformin-mediated downregulation of E2F1 in ovariectomized mice could downregulate BECN1 and BNIP3 levels, which subsequently perturbed the binding of BECN1 to BCL2. Furthermore, the disconnect between BECN1 and BCL2 was shown by BNIP3 overexpression. CONCLUSION: In summary, we demonstrated the effect and underlying mechanism of metformin on OVX-induced bone loss, which could be, at least in part, ascribed to its role in downregulating autophagy during osteoclastogenesis via E2F1-dependent BECN1 and BCL2 downregulation, suggesting that metformin or E2F1 inhibitor is a potential agent against postmenopausal bone loss. Video abstract.


Asunto(s)
Resorción Ósea , Metformina , Osteoporosis Posmenopáusica , Humanos , Ratones , Femenino , Animales , Osteoclastos , Osteoporosis Posmenopáusica/metabolismo , Metformina/farmacología , Resorción Ósea/tratamiento farmacológico , Autofagia , Hipoglucemiantes/metabolismo , Hipoglucemiantes/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Diferenciación Celular , Ligando RANK/metabolismo , Factor de Transcripción E2F1/metabolismo
18.
J Nerv Ment Dis ; 210(7): 541-546, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35766547

RESUMEN

ABSTRACT: Psychiatric disorders (depression/anxiety) and sleep quality are linked to coronary artery disease (CAD). CAD patients often complain of various physical symptoms (PSs), which are not only organic changes of biological origin, but also somatization of mental illness. PSs also affect CAD progression. However, the relationship between psychiatric disorders/sleep quality and PS in CAD is less studied, which this study aims to clarify. This cross-sectional observational study was conducted on the first 305 CAD patients diagnosed with PS by Patient Health Questionnaire-15. They were compared with 521 other CAD patients showing no PS. On multivariate analysis, sex, age, family history, psychiatric disorders, and sleep quality were the significant independent predictors of PS. A significant correlation was found between PS severity and the severity of both psychiatric disorders and sleep quality. Further studies are warranted to explore the impact of psychological and sleep intervention on PS and long-term outcomes.


Asunto(s)
Enfermedad de la Arteria Coronaria , Trastornos Mentales , Trastornos del Sueño-Vigilia , Ansiedad , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/psicología , Estudios Transversales , Depresión , Humanos , Trastornos Mentales/epidemiología , Trastornos Mentales/etiología , Calidad del Sueño , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/etiología , Encuestas y Cuestionarios
19.
J Nerv Ment Dis ; 210(12): 935-942, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36044660

RESUMEN

ABSTRACT: This study aims to investigate the relationship between trait anxiety and mental resilience in marathoners and the general population. The study recruited 135 marathoners and 140 members of the general population. Trait anxiety and mental resilience were measured by the State-Trait Anxiety Scale and the Chinese version of the Connor-Davidson Resilience Scale. The amount of weekly exercise resulted in significant differences in the trait anxiety ( F = 6.358, p < 0.01) and mental resilience ( F = 5.996, p < 0.05) levels of the general population and marathoners. Age led to a significant difference in the trait anxiety of marathoners ( F = 10.890, p < 0.01). The half marathoners' daily exercise program is most suitable for the general population for reducing trait anxiety level and increasing mental resilience. Furthermore, marathoners showed lower trait anxiety and higher mental resilience. Therefore, long-term marathon adherence can help improve mental health.


Asunto(s)
Ansiedad , Resiliencia Psicológica , Humanos , Ansiedad/psicología , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/terapia , Encuestas y Cuestionarios , Salud Mental , China/epidemiología
20.
Heart Surg Forum ; 25(5): E778-E783, 2022 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-36602401

RESUMEN

OBJECTIVE: Factors leading to an unplanned return to the cardiac intensive care unit (CICU) in children after congenital heart disease and their impact on mortality have not been well characterized. We sought to determine the incidence and outcomes of unplanned return to the CICU. A secondary objective was to identify risk factors. METHODS: Retrospective analysis of the registration data collected by our unit. The study subjects included postoperative patients with congenital heart disease who survived to initial transfer out of the CICU. Patients who unexpectedly returned to the CICU due to an acute change in clinical status were defined as unplanned returns. Demographic, preoperative, intraoperative, and postoperative variables were assessed. Univariate comparisons were performed between the return group and non-return group, and multivariate regression analysis was performed to identify potential risk factors for unplanned return to the CICU. RESULTS: Of the 531 children who met the inclusion criteria, 29 were unplanned returns to the CICU. Respiratory symptoms (41.4%) and cardiac symptoms (44.8%) were the most common reasons for returning to the CICU. Patients with unplanned returns had a higher mortality rate (13.8% vs. 0.56%, P < 0.01). In multivariate analysis, unplanned CICU admission was associated with chromosomal abnormalities (P < 0.01), longer ventilator duration (P < 0.01), and more prolonged cardiopulmonary bypass (P < 0.01) was associated with a return to independence. CONCLUSIONS: Unplanned return to the CICU during the same hospital stay was uncommon but associated with higher mortality. Chromosomal abnormalities, longer ventilator use duration, and prolonged CPB were significant risk factors for the entire cohort. We hope to minimize the impact of unplanned return after congenital heart disease surgery by changing the process of transferring these high-risk postoperative patients out of the CICU and early postoperative care.


Asunto(s)
Cardiopatías Congénitas , Unidades de Cuidados Intensivos , Humanos , Niño , Estudios Retrospectivos , Incidencia , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/cirugía , Cardiopatías Congénitas/diagnóstico , Factores de Riesgo , Tiempo de Internación
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