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1.
Heliyon ; 10(11): e32613, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38961951

RESUMEN

Entrepreneurial networks play an important role in identifying and exploiting entrepreneurial opportunities and the growth of entrepreneurial ambidexterity. This exploratory research aimed to explore the role of entrepreneurial networks on entrepreneurial ambidexterity with the mediating effect of novelty ecosystem and the moderating role of entrepreneurial intensity. The data is collected from 347 SME owners and managers of manufacturing and service industries in Jiangsu province, China. The hypotheses are analyzed using the partial least squares structural equation modeling PLS-SEM method. The results indicate that entrepreneurial networks are significantly associated with entrepreneurial ambidexterity. Moreover, findings show that the novelty ecosystem positively influences the association between entrepreneurial networks and entrepreneurial ambidexterity. Furthermore, results show that entrepreneurial intensity significantly moderated the relationship between novelty ecosystem and entrepreneurial ambidexterity. Lastly, the discussion and implications are elaborated in this study.

2.
Neuromolecular Med ; 26(1): 29, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014255

RESUMEN

Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST) has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25 mg/kg per day for 4 weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD.


Asunto(s)
Apoptosis , Demencia Vascular , Hipocampo , Trastornos de la Memoria , Neuronas , Fármacos Neuroprotectores , Estrés Oxidativo , Ratas Sprague-Dawley , Xantófilas , Animales , Xantófilas/uso terapéutico , Xantófilas/farmacología , Hipocampo/efectos de los fármacos , Demencia Vascular/tratamiento farmacológico , Ratas , Masculino , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/etiología , Estrés Oxidativo/efectos de los fármacos , Neuronas/efectos de los fármacos , Apoptosis/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Muerte Celular/efectos de los fármacos , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Prueba del Laberinto Acuático de Morris/efectos de los fármacos
3.
Front Pediatr ; 12: 1374150, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39035464

RESUMEN

Degos disease also known as malignant atrophic papulosis (MAP), is an autoinflammatory disease that mainly affects small- to medium-sized arteries. Gastrointestinal and nervous system are most commonly affected systems. Herein, we reported a case of Degos disease with disease onset during infantile and had severe neurological involvement.

4.
Nat Commun ; 15(1): 6215, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043664

RESUMEN

Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Recurrencia Local de Neoplasia , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Femenino , Recurrencia Local de Neoplasia/genética , Persona de Mediana Edad , Anciano , Pronóstico , Genómica/métodos , Adulto , Estadificación de Neoplasias , Aprendizaje Profundo , Supervivencia sin Enfermedad
5.
Respir Res ; 25(1): 283, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39020401

RESUMEN

BACKGROUND: Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis. METHODS: We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up. RESULTS: We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p < 0.001) with the time to the next exacerbation in bronchiectasis. CONCLUSION: We have revealed the pathogenic microbial spectrum in lower airways and the negative correlation of PPM colonization with the time to the next exacerbation in bronchiectasis. These results suggested that pathogens contribute to the progression of bronchiectasis.


Asunto(s)
Bronquiectasia , Humanos , Bronquiectasia/microbiología , Bronquiectasia/diagnóstico , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Líquido del Lavado Bronquioalveolar/microbiología , Estudios de Cohortes , Estudios de Seguimiento , Adulto , Progresión de la Enfermedad , Estudios Longitudinales
6.
Mol Ther Methods Clin Dev ; 32(2): 101270, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38883976

RESUMEN

Successful cell and gene therapy clinical trials have resulted in the US Food and Drug Administration and European Medicines Agency approving their use for treatment of patients with certain types of cancers and monogenetic diseases. These novel therapies, which rely heavily on lentiviral vectors to deliver therapeutic transgenes to patient cells, have driven additional investigations, increasing demand for both pre-clinical and current Good Manufacturing Practices-grade viral vectors. To better support novel studies by improving current production methods, we report the development of a genetically modified HEK293T-based cell line that is null for expression of both Protein Kinase R and Beta-2 microglobulin and grows in suspension using serum-free media, SJ293TS-DPB. Absence of Protein Kinase R increased anti-sense lentiviral vector titers by more than 7-fold, while absence of Beta-2 microglobulin, a key component of major histocompatibility complex class I molecules, has been reported to reduce the immunogenicity of lentiviral particles. Furthermore, we describe an improved methodology for culturing SJ293TS-DPB that facilitates expansion, reduces handling, and increases titers by 2-fold compared with previous methods. SJ293TS-DPB stably produced lentiviral vectors for over 4 months and generated lentiviral vectors that efficiently transduce healthy human donor T cells and CD34+ hematopoietic stem cells.

7.
Molecules ; 29(11)2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38893390

RESUMEN

This study details the rational design and synthesis of Cu2ZnSnS4 (CZTS)-doped anatase (A) heterostructures, utilizing earth-abundant elements to enhance the efficiency of solar-driven water splitting. A one-step hydrothermal method was employed to fabricate a series of CZTS-A heterojunctions. As the concentration of titanium dioxide (TiO2) varied, the morphology of CZTS shifted from floral patterns to sheet-like structures. The resulting CZTS-A heterostructures underwent comprehensive characterization through photoelectrochemical response assessments, optical measurements, and electrochemical impedance spectroscopy analyses. Detailed photoelectrochemical (PEC) investigations demonstrated notable enhancements in photocurrent density and incident photon-to-electron conversion efficiency (IPCE). Compared to pure anatase electrodes, the optimized CZTS-A heterostructures exhibited a seven-fold increase in photocurrent density and reached a hydrogen production efficiency of 1.1%. Additionally, the maximum H2 production rate from these heterostructures was 11-times greater than that of pure anatase and 250-times higher than the original CZTS after 2 h of irradiation. These results underscore the enhanced PEC performance of CZTS-A heterostructures, highlighting their potential as highly efficient materials for solar water splitting. Integrating Cu2ZnSnS4 nanoparticles (NPs) within TiO2 (anatase) heterostructures implied new avenues for developing earth-abundant and cost-effective photocatalytic systems for renewable energy applications.

8.
Lab Chip ; 24(14): 3528-3535, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38940766

RESUMEN

Optical detection is an indispensable part of microfluidic systems for nutrient determination in seawater. Coupling total internal reflection capillaries with microfluidic chips is a practical alternative to increase the optical path length for high-sensitivity and a low detection limit in colorimetric assays, which has not been applied in microfluidic devices for seawater nutrients. Here, we present an online microfluidic system which integrated a total internal reflection capillary made of Teflon AF 2400 for the high-sensitivity detection of nitrite and nitrate in seawater. The off-chip capillary lengthens the optical path without changing the internal flow path of the microfluidic chip, enhancing the sensitivity, reducing the detection limit and widening the dynamic range of the system, which significantly improves the performance of the microfluidic system based on wet-chemistry. The detection limit for nitrite is 0.0150 µM using an external 20 cm capillary and 0.0936 µM using an internal 5 cm absorption cell, providing an over 6-fold improvement. Laboratory analysis of surface seawater samples collected from the South China Sea with this system and a one-month online deployment of an autonomous analyzer developed based on this system at a station revealed correlations between the nitrite and nitrate with tide, salinity and chlorophyll over slight variations and narrow ranges, demonstrating the high-sensitivity of this method.

9.
Insect Sci ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38772748

RESUMEN

C-type lectins (CTLs) act as pattern recognition receptors (PRRs) to initiate the innate immune response in insects. A CTL with dual carbohydrate recognition domains (CRDs) (named immulectin-4 [IML-4]) was selected from the Ostrinia furnacalis transcriptome dataset for functional studies. We cloned the full-length complementary DNA of O. furnacalis IML-4 (OfIML-4). It encodes a 328-residue protein with a Glu-Pro-Asn (EPN) and Gln-Pro-Asp (QPD) motifs in 2 CRDs, respectively. OfIML-4 messenger RNA levels increased significantly upon the bacterial and fungal infection. Recombinant OfIML-4 (rIML-4) and its individual CRDs (rCRD1 and rCRD2) exhibited the binding ability to various microorganisms including Escherichia coli, Micrococcus luteus, Pichia pastoris, and Beauveria bassiana, and the cell wall components including lipopolysaccharide from E. coli, peptidoglycan from M. luteus or Bacillus subtilis, and curdlan from Alcaligenes faecalis. The binding further induced the agglutination of E. coli, M. luteus, and B. bassiana in the presence of calcium, the phagocytosis of Staphylococcus aureus by the hemocytes, in vitro encapsulation and melanization of nickel-nitrilotriacetic acid beads, and a significant increase in phenoloxidase activity of plasma. In addition, rIML-4 significantly enhanced the phagocytosis, nodulation, and resistance of O. furnacalis to B. bassiana. Taken together, our results suggest that OfIML-4 potentially works as a PRR to recognize the invading microorganisms, and functions in the innate immune response in O. furnacalis.

10.
Infect Drug Resist ; 17: 1771-1780, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736435

RESUMEN

Angiotensin-converting enzyme 2 (ACE2) is an important regulator of the Renin-Angiotensin System (RAS). Additionally, it has been identified as a functional receptor for the Coronavirus. Research indicates that ACE2 plays a role in the regulation of cardiovascular systems by modulating blood pressure and electrolyte balance. Its role in pulmonary diseases has also garnered significant attention due to the widespread prevalence of Coronavirus. There is solid evidence linking ACE2 to other pulmonary diseases, including chronic obstructive pulmonary disease, acute respiratory distress syndrome, allergic asthma, among others. However, the exact pathological and physiological mechanisms of ACE2 in these diseases remain elusive. Our research aims to review and explore the latest advancements in ACE2-related studies in pulmonary diseases. These findings have the potential to open new avenues for utilizing ACE2 as a potential biomarker for early diagnosis and monitoring of pulmonary diseases.

11.
Bioorg Chem ; 148: 107427, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38728911

RESUMEN

Histone acetyltransferase CREB-binding protein (CBP) and its homologous protein p300 are key transcriptional activators that can activate oncogene transcription, which present promising targets for cancer therapy. Here, we designed and synthesized a series of p300/CBP targeted low molecular weight PROTACs by assembling the covalent ligand of RNF126 E3 ubiquitin ligase and the bromodomain ligand of the p300/CBP. The optimal molecule A8 could effectively degrade p300 and CBP through the ubiquitin-proteasome system in time- and concentration-dependent manners, with half-maximal degradation (DC50) concentrations of 208.35/454.35 nM and 82.24/79.45 nM for p300/CBP in MV4-11 and Molm13 cell lines after 72 h of treatment. And the degradation of p300/CBP by A8 is dependent on the ubiquitin-proteasome pathway and its simultaneous interactions with the target proteins and RNF126. A8 exhibits good antiproliferative activity in a series of p300/CBP-dependent cancer cells. It could transcriptionally inhibit the expression of c-Myc, induce cell cycle arrest in the G0/G1 phase and apoptosis in MV4-11 cells. This study thus provided us a new chemotype for the development of drug-like PROTACs targeting p300/CBP, which is expected to be applied in cancer therapy.


Asunto(s)
Antineoplásicos , Proliferación Celular , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Ubiquitina-Proteína Ligasas , Factores de Transcripción p300-CBP , Humanos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/antagonistas & inhibidores , Factores de Transcripción p300-CBP/metabolismo , Factores de Transcripción p300-CBP/antagonistas & inhibidores , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Estructura Molecular , Apoptosis/efectos de los fármacos , Línea Celular Tumoral
12.
World J Gastroenterol ; 30(17): 2354-2368, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38813048

RESUMEN

BACKGROUND: Difficulty in obtaining tetracycline, increased adverse reactions, and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy. Therefore, the search for new alternative drugs has become one of the research hotspots. In recent years, minocycline, as a semisynthetic tetracycline, has demonstrated good potential for eradicating Helicobacter pylori (H. pylori) infection, but the systematic evaluation of its role remains lacking. AIM: To explore the efficacy, safety, and compliance of minocycline in eradicating H. pylori infection. METHODS: We comprehensively retrieved the electronic databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang database as of October 30, 2023, and finally included 22 research reports on H. pylori eradication with minocycline-containing regimens as per the inclusion and exclusion criteria. The eradication rates of H. pylori were calculated using a fixed or a random effect model, and the heterogeneity and publication bias of the studies were measured. RESULTS: The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall H. pylori eradication rates, reaching 82.3% [95% confidence interval (CI): 79.7%-85.1%] in the intention-to-treat analysis and 90.0% (95%CI: 87.7%-92.4%) in the per-protocol analysis. The overall safety and compliance of the minocycline-containing regimens were good, demonstrating an overall incidence of adverse reactions of 36.5% (95%CI: 31.5%-42.2%). Further by traditional meta-analysis, the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects. Most of the adverse reactions were mild to moderate and well-tolerated, and dizziness was relatively prominent in the minocycline-containing regimens (16%). CONCLUSION: The minocycline-containing regimens demonstrated good efficacy, safety, and compliance in H. pylori eradication. Minocycline has good potential to replace tetracycline for eradicating H. pylori infection.


Asunto(s)
Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Minociclina , Humanos , Minociclina/efectos adversos , Minociclina/administración & dosificación , Minociclina/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Quimioterapia Combinada/métodos , Resultado del Tratamiento , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Cumplimiento de la Medicación
13.
Water Res ; 255: 121548, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38569357

RESUMEN

Rhizoremediation of wetland plants is an environmentally friendly strategy for sediment phosphorous (P) removal, the basic underlying principle of which is the complex interactions between roots and microorganisms. This study investigated the immobilization and mobilization mechanisms of P in the rhizosphere of wetland plants using high-resolution spatial visualization techniques and metagenomic sequencing. Two-dimensional visualization of the spatial distribution of P, iron (Fe) and manganese (Mn) indicated that the sequestration of Fe-oxides rather than Mn-oxides caused the depletion of labile P, resulting in an increase in the Fe-adsorbed P fraction. Plants altered the rhizospheric environments and P-cycling microbial community to mobilize low-availability P from sediments. Mineral P solubilization and organic P mineralization were enhanced by local acidification and increased phosphatase activity, respectively. Microbial P mobilization also increased with increasing relative abundances of P solubilization and mineralization genes (gcd and phnW) and decreasing P transportation genes (ugpA, ugpB, and pit) genes in the rhizosphere. These processes led to the remobilization of 10.04 % of inorganic P, and 15.23 % of organic P, in the rhizosphere during the incubation period. However, the resupply of P via the above processes did not compensate for the depletion of rhizospheric P via root uptake and mineral sequestration. Our results provide novel insights into the mechanisms of rhizospheric P cycling, which will help to inform future phytoremediation strategies.

14.
J Phys Chem A ; 128(17): 3273-3284, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38635947

RESUMEN

Herein, we report a computation study based on the density functional theory calculations to understand the mechanism and ligand effect of the base-stabilized dialumenes toward dihydrogen activation. Among all of the examined modes of dihydrogen activation using the base-stabilized dialumene, we found that the concerted 1,2-hydrogenation of the Al═Al double bond is kinetically more preferable. The concerted 1,2-hydrogenation of the Al═Al double bond adopts an electron-transfer model with certain asynchrony. That is, the initial electron donation from the H-H σ bonding orbital to the empty 3p orbital of the Al1 center is followed by the backdonation from the lone pair electron of the Al2 center to the H-H σ antibonding orbital. Combined with the energy decomposition analysis on the transition states of the concerted 1,2-hydrogenation of the Al═Al double bond and the topographic steric mapping analysis on the free dialumenes, we ascribe the higher reactivity of the aryl-substituted dialumene over the silyl-substituted analogue in dihydrogen activation to the stronger electron-withdrawing effect of the aryl group, which not only increases the flexibility of the Al═Al double bond but also enhances the Lewis acidity of the Al═Al core. Consequently, the aryl-substituted dialumene fragment suffers less geometric deformation, and the orbital interactions between the dialumene and dihydrogen moieties are more attractive during the 1,2-hydrogenation process. Moreover, our calculations also predict that the Al═Al double bond has a good tolerance with the stronger electron-withdrawing group (-CF3) and the weaker σ-donating N-heterocyclic carbene (NHC) analogue (e.g., triazol carbene and NHSi). The reactivity of the dialumene in dihydrogen activation can be further improved by introducing these groups as the supporting ligand and the stabilizing base on the Al═Al core, respectively.

15.
Artículo en Inglés | MEDLINE | ID: mdl-38686909

RESUMEN

OBJECTIVE: To study the etiological characteristics of community-acquired pneumonia (CAP) combined with type 2 diabetes (T2D), providing a reference for early clinical diagnosis and treatment of the disease. METHODS: We selected a total of 93 patients with CAP and analyzed their metagenomics nextgeneration sequencing (mNGS) data. The case group comprised 46 patients with combined CAP/T2D, and the control group comprised 47 patients without diabetes. We analyzed the pathogenic findings of the two groups. RESULTS: There were statistically significant differences in age between the two groups (P = 0.001). Leukocytes (P = 0.012), blood platelets (P = 0.034), fibrinogen (P = 0.037), D-dimer (P = 0.000), calcitonin ogen (P = 0.015), ultrasensitive C-reactive protein or C-reactive protein (CRP) (P = 0.000), serum amyloid A (P = 0.000), and erythrocyte sedimentation rate (P = 0.003) were higher in the case group than in the control group. Albumin was lower in the case group than in the control group. All differences were statistically significant. The infection rates of Klebsiella pneumoniae (P = 0.030), Pseudomonas aeruginosa (P = 0.043), and Candida albicans (P = 0.032) were significantly different between the two groups. CONCLUSION: Compared with those without diabetes, the infection rates of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans were higher in patients with combined CAP/T2D.


Asunto(s)
Infecciones Comunitarias Adquiridas , Diabetes Mellitus Tipo 2 , Diagnóstico Precoz , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/microbiología , Diabetes Mellitus Tipo 2/epidemiología , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/sangre , Infecciones Comunitarias Adquiridas/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neumonía/diagnóstico , Neumonía/sangre , Neumonía/microbiología , Estudios de Casos y Controles , Metagenómica/métodos , Adulto , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/sangre , Neumonía Bacteriana/epidemiología
16.
J Transl Med ; 22(1): 316, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38549133

RESUMEN

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.


Asunto(s)
Propofol , Sepsis , Ratones , Humanos , Animales , Propofol/farmacología , Propofol/uso terapéutico , Propofol/metabolismo , Receptor Toll-Like 4/metabolismo , Modelos Animales de Enfermedad , Macrófagos/metabolismo , Sepsis/complicaciones , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo
17.
Quant Imaging Med Surg ; 14(3): 2213-2224, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38545056

RESUMEN

Background: There is an increasing evidence that pulmonary vein (PV) enlargement is associated with atrial fibrillation (AF); however, the predictive value of PV enlargement in AF recurrence remains unclear. This study sought to evaluate whether PV volume quantification derived from cardiac computed tomographic angiography (CCTA) could serve as a predictive indicator of the success of the catheter ablation (CA) procedure. Methods: The data of 160 patients diagnosed with AF who underwent both CCTA and CA treatments from January to June 2020 were retrospectively examined; the CCTA was conducted before the CA surgery. The study focused on documenting the PV structure, and the volume of the PV and left atrium (LA). The clinical, CCTA, and echocardiographic predictors of the recurrence and no-recurrence groups were compared. A multivariable logistic regression analysis was performed to adjust for confounders. Receiver operating characteristic (ROC) curves were analyzed to assess the predictive performance of the predictors of AF recurrence. Results: Of the 160 patients [55.6% male, 62.00 (55.25-68.00) years, 23.1% with persistent AF], 45 (28.1%) experienced AF recurrence within a one-year period. Notably, patients with AF recurrence had elevated CHADS2 scores (P=0.020) and increased LA and PV volumes (P<0.05). Patients with persistent AF (n=37) had significantly larger LA volume indexes (P<0.001) than those with paroxysmal AF, but there was no difference between the two groups in terms of the PV maximum volume index (P=0.200). Moreover, the PV maximum volume index [odds ratio (OR): 1.244, 95% confidence interval (CI): 1.008-1.536, P=0.042] and the LA minimum volume index (OR: 1.026, 95% CI: 1.001-1.052, P=0.038) were found to be significant predictors of AF recurrence. The ROC curves revealed that the PV maximum volume index threshold for predicting AF recurrence was 7.13 mL/m2, with a sensitivity of 84.4% and a specificity of 34.8% [area under the curve (AUC): 0.635, 95% CI: 0.540-0.730, P=0.008], and the LA minimum volume index threshold for predicting AF recurrence was 46.16 mL/m2, with a sensitivity of 88.9% and a specificity of 31.3% (AUC: 0.629, 95% CI: 0.534-0.723, P=0.012). A sub-analysis of patients with a lower left atrial dimension (LAD ≤38 mm in females, LAD ≤40 mm in males, n=120) demonstrated that the PV maximum volume index was a noteworthy indicator of AF recurrence (OR: 1.443: 95% CI: 1.145-1.820, P=0.002). Conversely, no significant correlation between AF recurrence and the LA volume index was found. The AUC value for the PV maximum volume index predictive of recurrent AF was 0.680 (95% CI: 0.577-0.781, P=0.003), with a sensitivity of 75.8%, specificity of 54%, and the cut-off value of the maximum AUC was 7.89 mL/m2. Conclusions: PV volume, derived from CCTA, may help to predict the recurrence of AF after CA, and is superior to the LA size in patients with less pronounced LA enlargement.

18.
Heliyon ; 10(6): e28075, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38533028

RESUMEN

The evolution of the hotel industry's corporate environmental performance cannot be realized without employees acting in an environmentally friendly manner, such as low carbon behaviour. However, a thorough analysis of the factors influencing employees' low-carbon behaviour and hotels' corporate environmental performance has not yet been done. To overcome this literature gap and envision the social identity theory, this study evaluated how employees' green self-efficacy, environmental awareness, and perceived corporate environmental responsibility facilitate staff low carbon behaviour. Also, the study explored the moderation role of employees' moral reflectiveness. Through a purposive sampling technique, data was collected from 455 employees in the hotel industry in South Africa. The partial least squares structural equation model method examined the proposed hypothesis. The empirical findings revealed that: (1) employees' green self-efficacy, environmental awareness, and perceived corporate environmental responsibility positively influence their low carbon behaviour. (2) Employees' low carbon behaviour directly and positively affected hotels' corporate environmental performance. (3) The outcome supported the moderation effect of employees' moral reflectiveness on the linkage between green self-efficacy and low-carbon behaviour. The practical and theoretical implications are discussed. The limitations and areas of future research are further outlined.

19.
Huan Jing Ke Xue ; 45(3): 1428-1438, 2024 Mar 08.
Artículo en Chino | MEDLINE | ID: mdl-38471858

RESUMEN

To understand the water pollution status and environmental risks of Changshou Lake, the concentrations of heavy metals (Cr, Cu, Zn, As, Cd, and Pb) in the water were collected and analyzed during different seasons. The study investigated temporal and spatial variations, distribution characteristics, pollution levels, and health risks associated with heavy metals in Changshou Lake. The results showed that all six heavy metals were below than the Class Ⅰ standard of the Surface Water Environmental Quality Standard (GB 3838-2002), but recent years have witnessed an increasing trend, with Cu, As, and Pb showing a significant increase (P<0.05). The temporal and spatial distributions of these heavy metals were different. Temporally, Cr and Cd concentrations in surface water were higher in summer, As and Zn were higher in spring, and Pb and Cu were higher in autumn and winter. Spatially, the concentrations of Cr, As, Cu, Zn, and Pb showed higher concentrations in the southern outlet of the reservoir, the northwestern Longxi River inlet, and the central part of the reservoir, whereas Cd was higher in the northern stagnant area. The overall levels of heavy metals in the water body of Changshou Lake were low, with Cr and Cu slightly polluted, while other heavy metals were identified as having an insignificant pollution level. Drinking water was the primary exposure pathway to carcinogenic and non-carcinogenic heavy metals in surface water bodies. The health risk values of Cr and As in water bodies were high, ranging from 6.2×10-10 to 3.0×10-4 and 5.1×10-8 to 3.9×10-5, respectively. The corresponding contribution rates for children and adults to the total health risk were high, with Cr accounting for 87.18% and 87.20%, respectively, while As accounted for 12.73% and 12.71%, respectively. Therefore, it is crucial to prioritize environmental risks associated with Cr and Cu, as well as the health risks associated with Cr and As in Changshou Lake These findings provide a scientific foundation for water pollution control and environmental quality improvement in Changshou Lake, and rational development and utilization of water resources.


Asunto(s)
Agua Potable , Metales Pesados , Contaminantes Químicos del Agua , Cadmio , China , Monitoreo del Ambiente , Sedimentos Geológicos , Lagos/análisis , Plomo , Metales Pesados/análisis , Medición de Riesgo , Contaminantes Químicos del Agua/análisis , Humanos , Niño , Adulto
20.
Sci Rep ; 14(1): 5976, 2024 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-38472256

RESUMEN

We performed this cohort study to investigate whether the myocardial bridge (MB) affects the fat attenuation index (FAI) and to determine the optimal cardiac phase to measure the volume and the FAI of pericoronary adipose tissue (PCAT). The data of 300 patients who were diagnosed with MB of the left anterior descending (LAD) coronary artery were retrospectively analyzed. All of patients were divided into the MB group and the MB with atherosclerosis group. In addition, 104 patients with negative CCTA results were enrolled as the control group. There was no significant difference between FAI values measured in systole and diastole (P > 0.05). There was no significant difference in FAI among the MB group, the MB with atherosclerosis group, and the control group (P > 0.05). In MB with atherosclerosis group, LAD stenosis degree (< 50%) (OR = 0.186, 95% CI 0.036-0.960; P = 0.045) and MB located in the distal part of LAD opening (OR = 0.880, 95% CI 0.789-0.980; P = 0.020) were protective factors of FAI value. A distance (from the LAD opening to the proximal point of the MB) of 29.85 mm had the highest predictive value for abnormal FAI [area under the curve (AUC), 0.798], with a sensitivity of 81.1% and a specificity of 74.6%.


Asunto(s)
Aterosclerosis , Enfermedad de la Arteria Coronaria , Puente Miocárdico , Humanos , Angiografía Coronaria/métodos , Estudios de Cohortes , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Vasos Coronarios , Tejido Adiposo
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