Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 597
Filtrar
1.
Virus Genes ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235696

RESUMEN

Atopic dermatitis (AD) is accompanied by changes in skin microbiota, in which abnormal colonization of Staphylococcus aureus is particularly common. The antibiotic treatment is prone to destroy the commensal bacterial community, further exacerbating the microbiome dysbiosis. Elimination of S. aureus through phage-targeted therapies presents a promising method in the treatment strategy of AD. In this study, we isolated a novel phage SAP71, which specifically lysed S. aureus. Genome sequencing showed that SAP71 contained no virulence, lysogenic, or antimicrobial resistance genes, making this lytic phage a potential agent for phage therapy. Moreover, we demonstrated that phage SAP71 was able to significantly improve the skin lesions, reduce the bacterial loads in the skin, and prevent the development of AD-like skin pathological changes in an AD model. In short, phage SAP71 was demonstrated to effectively treat S. aureus infection in AD, which provided a theoretical basis for the clinical phage therapy of AD.

2.
Heliyon ; 10(17): e37617, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39290278

RESUMEN

Background: Ferroptosis is a new type of programmed cell death. Although ferroptosis has been studied in various aspects, there has been no visual analysis of ferroptosis in coronavirus disease 2019 (COVID-19) to date. It is still a global health concern of the COVID-19 pandemic worldwide, three years after its outbreak. Yet the emergence of the mutant strain Omicron has caused a fourth wave of infections in many countries. The pathogenesis of COVID-19 is still undergoing extensive exploration, which holds paramount importance in mitigating future epidemics. Methods: For this study, CiteSpace 6.2 R4 software was used for bibliometric and visual atlas analysis of ferroptosis-related research, and the Genecards database was used to mine ferroptosis and COVID-19-related genes. Results: We found increasing studies about ferroptosis. China and the United States have demonstrated robust scientific innovation over recent years, with extensive collaboration between their institutions and authors. Ferroptosis and COVID-19 were seen to have 13 shared genes, which may be new targets for the treatment of COVID-19 in the future. Most of the shared genes are enriched in tumor necrosis factor (TNF) pathways. The majority of those genes are up-regulated under the cellular response to oxidative stress. Genes including Tumour necrosis factor (TNF), RELA proto-oncogene (RELA), Activating transcription factor 4 (ATF4), Cytochrome b-245 beta chain (CYBB), Jun proto-oncogene (JUN), Mitogen-activated protein kinase 1 (MAPK1) and Heme oxygenase 1 (HMOX1), maybe a breakthrough for ferroptosis and COVID-19. Whilst previous research has shown there to be a relationship between ferroptosis and COVID-19, the specific role of ferroptosis remained unclear. Our study aimed to analyze the research status of ferroptosis and its relationship with COVID-19, to provide a useful reference for further prevention and treatment of COVID-19. Overall, uncovering the role of ferroptosis in SARS-CoV-2 infection is important for the development of new treatment strategies for COVID-19.

3.
Front Pharmacol ; 15: 1396378, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39290866

RESUMEN

Objective: To mine and analyze adverse events (AEs) related to proteasome inhibitors in multiple myeloma based on the FDA Adverse Event Reporting System (FAERS), providing references for rational clinical medication. Methods: AE data related to multiple myeloma proteasome inhibitors were collected from the FAERS from the first quarter of 2010 to the first quarter of 2024. Signal mining of AEs was conducted using the reporting odds ratio method and Bayesian confidence propagation neural network method. Results: A total of 8,805 reports for bortezomib, 5,264 for carfilzomib, and 8,771 for ixazomib were collected, with corresponding AE signals of 474, 279, and 287, respectively, involving 23, 21, and 22 System Organ Classes (SOCs). The report information for the three drugs tended to be consistent: more cases were reported in males than in females; the majority of patients were 65 years and over; AEs mostly occurred within 6 months of medication; the outcomes primarily consisted of hospitalization, prolonged hospital stay, and other serious adverse events; the primary reporting country was the United States. The most affected SOCs were infections and infestations, general disorders and administration site conditions, and blood and lymphatic system disorders. Conclusion: The overall distribution of AEs for the three multiple myeloma proteasome inhibitors was consistent, but there were certain differences in specific AE signal characteristics, which should be noted in clinical applications.

4.
Sci Rep ; 14(1): 21460, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271932

RESUMEN

To address the problem of dense crowd face detection in complex environments, this paper proposes a face detection model named Deep and Compact Face Detection (DCFD), which adopts an improved lightweight EfficientNetV2 network to replace the backbone network of RetinaFace. A large kernel attention mechanism is introduced to address the face detection task more accurately. The backbone network, an improved efficient channel attention (ECA) mechanism, is added to further improve the algorithm performance. The feature fusion module is an improved neural architecture search feature pyramid network (NAS-FPN) that significantly improves the face detection accuracy in different scenes. To balance the training process of positive and negative samples, we use the focus loss function to replace the traditional cross-entropy loss function. In different environments, the DCFD algorithm has shown efficient face detection performance. This algorithm provides not only a feasible and effective solution for solving the problem of face detection in dense groups but also an important basis for improving the accuracy of face detection models in practical applications.

5.
J Cosmet Dermatol ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177015

RESUMEN

BACKGROUND: Keratosis pilaris (KP) is a prevalent benign dermatological condition characterized by small bumps at the hair follicles alongside surrounding redness, significantly impacting both aesthetics and mental well-being. OBJECTIVE: This study investigated the potential benefits of a non-cross-linked hyaluronic acid (HA) compound for treating KP. METHODS: A split-body, investigator-blinded, randomized, intraindividual comparative clinical trial was conducted. The non-cross-linked HA compound was injected into KP-affected regions on both upper arms. The treatment was delivered across four sessions scheduled at 4-week intervals. Blinded physicians and patients assessed differences in erythema, skin roughness, and overall scores between treated and control areas at the final follow-up visit. At the 12th and 24th weeks post-treatment, a four-point scale was utilized to assess subjects' perceived treatment efficacy. Additionally, dermoscopic images, histological alterations, and adverse events were monitored. RESULTS: Physician assessments revealed a significant reduction in roughness and overall scores for treated areas compared to controls. Patient self-assessments also reflected improvements in roughness, redness, and overall scores for treated sides at the final visit, with 35.71% of patients demonstrating sustained improvement in redness and 71.43% reporting persistent improvements in roughness at 24th weeks post-treatment. The dermatoscopic examinations revealed a notable enhancement in both the quantity of follicular plugs and the extent of erythema among the subjects in the treatment group. Histopathological outcomes also demonstrated improvement. CONCLUSION: This study suggests that the non-cross-linked HA compound effectively improves skin roughness and promotes hair shaft growth in KP treatment, demonstrating a favorable safety profile. These findings position it as a potentially viable alternative therapy in clinical practice.

6.
J Colloid Interface Sci ; 677(Pt B): 748-755, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39167966

RESUMEN

The heavy by-products generated on Zn anode surface decrease the active surface of Zn anodes and thus induce uneven Zn deposition, seriously reducing the service life of aqueous Zn-ion batteries (AZIBs). Herein, we propose an elimination strategy enabled by the coordination chemistry to dissolve the main by-products (Zn4SO4(OH)6·xH2O). Urea as a proof-of-concept has been applied as the reactivator in the electrolyte to catalytically produce highly active NH3 on the surface of the by-products. Then the NH3 can powerfully coordinate with the Zn2+ ion in the by-products to form the soluble complex [Zn(NH3)4]2+. Consequently, the proposed electrolyte can not only lead to the timely decomposition of the by-products to prevent the Zn anode from inactivation during cycling, but also repair the waste Zn anodes for reutilization. The action mechanism has been systematically demonstrated via theoretical simulation and experimental study. As a result, the high durability with ultrahigh cumulative capacity of 10,600 mAh cm-2 for the Zn||Zn symmetric cell has been achieved at 40 mA cm-2. Particularly, the dead Zn||Zn symmetric cells and Zn||LiFePO4 full cells have been successfully reactivated. This study lights a new route to extend the cell lifespan and reuse waste Zn-ion batteries.

7.
Biochem Biophys Res Commun ; 734: 150424, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39083974

RESUMEN

To explore the therapeutic effects along with the molecular mechanisms of epigallocatechin gallate (EGCG) in non-alcoholic fatty liver disease (NAFLD) treatment using network pharmacology as well as animal experiments. Firstly, the Traditional Chinese Medicine (TCM) Systems Pharmacology Database was searched to identify the potential targets of EGCG. The DisGeNET Database was used to screen the potential targets of NAFLD. The GeneCards Database was searched to identify related genes involved in pyroptosis. Subsequently, the intersecting genes of EGCG targeting pyroptosis to regulate NAFLD were obtained using a Venn diagram. Simultaneously, the aforementioned intersecting genes were used to construct a drug-disease target protein-protein interaction (PPI) network. The DAVID database was adopted for Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The main pathway-target network was determined. Next, the potential mechanism of EGCG targeting pyroptosis to regulate NAFLD was investigated and validated through in vivo experiments. 626 potential targets of EGCG, 447 target genes of NAFLD, and 568 potential targets of pyroptosis were identified. The number of common targets between EGCG, NAFLD, and pyroptosis was 266. GO biological process items and 92 KEGG pathways were determined based on the analysis results. Animal experiments demonstrated that EGCG could ameliorate body weight, glucolipid metabolism, steatosis, and liver injury, enhance insulin sensitivity, and improve glucose tolerance in NAFLD mice through the classical pathway of pyroptosis. EGCG could effectively treat NAFLD through multiple targets and pathways. It was concluded that EGCG ameliorates hepatocyte steatosis, pyroptosis, dyslipidemia, and inflammation in NAFLD mice fed a high-fat diet (HFD), and the protective mechanism could be associated with the NLRP3-Caspase-1-GSDMD classical pyroptosis pathway.

8.
Sci Rep ; 14(1): 16809, 2024 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-39039202

RESUMEN

Long-term exposure to hyperglycemic conditions leads to ß-cell dysfunction, particularly mitochondrial dysfunction, and inflammatory and oxidative stress responses, which are considered the primary causes of ß-cell death and the hallmarks of diabetes. Plant-active ingredients may play a key role in glycemic control. Epigallocatechin gallate (EGCG) is a characteristic catechin derived from tea that possesses anti-diabetic properties. Nonetheless, its underlying mechanisms remain elusive. Herein, the protective role of EGCG on high glucose (33 mM)-induced pancreatic beta cell dysfunction and its possible molecular mechanisms were investigated. Briefly, MIN6 cells were treated with glucose and EGCG (10 µM, 20 µM, and 40 µM) for 48 h. Our results revealed that EGCG dose-dependently restored mitochondrial membrane potential and concomitantly alleviated cell apoptosis. Mechanistically, the expression level of apoptotic protein BAX and Dynamic related protein 1 (DRP1) was significantly downregulated following EGCG treatment, whereas that of the anti-apoptotic protein BCL-2 was significantly upregulated. Taken together, EGCG alleviated high glucose-induced pancreatic beta cell dysfunction by targeting the DRP1-related mitochondrial apoptosis pathway and thus can serve as a nutritional intervention for the preservation of beta cell dysfunction in patients with type 2 diabetes mellitus.


Asunto(s)
Apoptosis , Catequina , Dinaminas , Glucosa , Células Secretoras de Insulina , Mitocondrias , Catequina/análogos & derivados , Catequina/farmacología , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Apoptosis/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Glucosa/metabolismo , Dinaminas/metabolismo , Dinaminas/genética , Animales , Ratones , Línea Celular , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo
9.
Expert Opin Drug Saf ; : 1-9, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39083396

RESUMEN

OBJECTIVE: The FDA Adverse Event Reporting System (FAERS) was used to mine and evaluate adverse events (AEs) associated with cyclin-dependent kinase (CDK) 4/6 inhibitors, thereby providing a reference for clinical rational drug use. METHODS: AE data related to CDK4/6 inhibitors from the first quarter of 2015 to the first quarter of 2023 were acquired from FAERS, while the signal mining was processed using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. RESULTS: The number of AE reports for CDK4/6 inhibitors was, respectively, 132,494 for palbociclib, 56,151 for ribociclib, and 7,014 for abemaciclib. The corresponding numbers of AE signals were 319, 517, and 59, with the number of involved System Organ Class (SOC) being 23, 23, and 15, mainly involving blood and lymphatic system disorders, respiratory, thoracic and mediastinal disorders, hepatobiliary disorders, skin and subcutaneous tissue disorders, etc. CONCLUSION: CDK4/6 inhibitors could lead to pulmonary toxicity, myelosuppression, skin reactions, etc. Special attention should be paid to abemaciclib for interstitial lung disease (ILD), erythema multiforme, and thrombosis risk; ribociclib for cardiac toxicity, hepatotoxicity, and musculoskeletal toxicity; palbociclib for neurocognitive impairment and osteonecrosis of the jaw.

10.
Proc Natl Acad Sci U S A ; 121(28): e2322972121, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38968116

RESUMEN

Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.


Asunto(s)
Reparación del ADN , Ubiquitina-Proteína Ligasas , Humanos , Roturas del ADN de Doble Cadena , Histonas/metabolismo , Histonas/genética , Poliubiquitina/metabolismo , Proteína 1 de Unión al Supresor Tumoral P53/metabolismo , Proteína 1 de Unión al Supresor Tumoral P53/genética , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación
11.
Science ; 385(6704): 68-74, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38963855

RESUMEN

Passive radiant cooling is a potentially sustainable thermal management strategy amid escalating global climate change. However, petrochemical-derived cooling materials often face efficiency challenges owing to the absorption of sunlight. We present an intrinsic photoluminescent biomass aerogel, which has a visible light reflectance exceeding 100%, that yields a large cooling effect. We discovered that DNA and gelatin aggregation into an ordered layered aerogel achieves a solar-weighted reflectance of 104.0% in visible light regions through fluorescence and phosphorescence. The cooling effect can reduce ambient temperatures by 16.0°C under high solar irradiance. In addition, the aerogel, efficiently produced at scale through water-welding, displays high reparability, recyclability, and biodegradability, completing an environmentally conscious life cycle. This biomass photoluminescence material is another tool for designing next-generation sustainable cooling materials.

12.
Phytomedicine ; 132: 155332, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38851983

RESUMEN

BACKGROUND: Xiaoyaosan (XYS), a traditional Chinese medicine formulation, has been used in the treatment of depression. However, no studies have yet identified the active compounds responsible for its antidepressant effects in the brain. STUDY DESIGN: We investigated the antidepressants effects of XYS and identified 18ß-glycyrrhetinic acid (18ß-GA) as the primary compound present in the brain following XYS injection. Furthermore, we explored the molecular mechanisms underlying the antidepressant-like effects of both XYS and 18ß-GA. METHODS: To investigate the antidepressant-like effects of XYS and elucidate the associated molecular mechanisms, we employed various methodologies, including cell cultures, the chronic social defeat stress (CSDS) model, behavioral tests, immunoprecipitation, quantitative PCR (qPCR) assays, Western blotting assays, luciferase assays, chromatin immunoprecipitation (ChIP) assays, immunofluorescence staining, and dendritic spine analysis. RESULTS: We identified 18ß-GA as the primary compound in the brain following XYS injection. In vitro, 18ß-GA was found to bind with ERK (extracellular signal-regulated kinase), subsequently activating ERK kinase activity toward both c-Jun and cAMP response element binding protein (CREB). Moreover, 18ß-GA activated brain-derived neurotrophic factor (BDNF) transcription by stimulating nuclear factor-erythroid factor 2-related factor 2 (Nrf2), c-Jun, and CREB, while also inhibiting methyl CpG binding protein 2 (MeCP2) both in vitro and in vivo. Chronic intraperitoneal (i.p.) administration of 18ß-GA exhibited prophylactic antidepressant-like effects in a CSDS model, primarily by activating BDNF transcription in the medial prefrontal cortex (mPFC). Interestingly, a single i.p. injection of 18ß-GA produced rapid and sustained antidepressant-like effects in CSDS-susceptible mice by engaging the BDNF-tropomyosin receptor kinase B (TrkB) signaling pathway in the mPFC. CONCLUSION: These findings suggest that the activation of BDNF transcription in the mPFC underlies the antidepressant-like effects of 18ß-GA, a key component of XYS in the brain.


Asunto(s)
Antidepresivos , Factor Neurotrófico Derivado del Encéfalo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Ácido Glicirretínico , Ratones Endogámicos C57BL , Derrota Social , Estrés Psicológico , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ácido Glicirretínico/farmacología , Ácido Glicirretínico/análogos & derivados , Antidepresivos/farmacología , Masculino , Medicamentos Herbarios Chinos/farmacología , Ratones , Estrés Psicológico/tratamiento farmacológico , Depresión/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , Receptor trkB/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo
13.
Chemistry ; 30(43): e202401693, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38837262

RESUMEN

The serious dendrite growth and H2O-induced side reactions on the Zn electrode lead to a significant fading in the cycling performance, hindering the development of commercial applications of aqueous Zn-ion batteries (AZIBs). Herein, a novel bifunctional network coating of dynamically cross-linking sodium alginate with trehalose has been rationally constructed on the Zn anode (Zn@AT). Firstly, the AT coating possesses abundant zinophilic oxygen-containing functional groups, which are able to induce uniform Zn2+ ion flux. Secondly, the AT coating as a solid barrier can effectively inhibit H2O-induced side reactions by lowering the activity of H2O molecules. More specially, based on the dynamic cross-linking, AT network coating is endowed with self-healing capacity during cycling for durable battery operation. Consequentially, Zn@AT anodes in symmetric cells can cycle stably for 2787 h at 2 mA cm-2/2 mAh cm-2, and even achieve a significantly long cycle performance of 1087 h at large charge/discharge depths of 10 mA cm-2/10 mAh cm-2. Moreover, the Zn@AT//MnO2 full cell shows excellent specific capacity of 175 mAh g-1 after 400 cycles. This study lights an effective strategy to enhance the durability of Zn electrodes in AZIBs.

14.
Chin J Integr Med ; 30(8): 747-758, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38900227

RESUMEN

The hippocampus is one of the most commonly studied brain regions in the context of depression. The volume of the hippocampus is significantly reduced in patients with depression, which severely disrupts hippocampal neuroplasticity. However, antidepressant therapies that target hippocampal neuroplasticity have not been identified as yet. Chinese medicine (CM) can slow the progression of depression, potentially by modulating hippocampal neuroplasticity. Xiaoyaosan (XYS) is a CM formula that has been clinically used for the treatment of depression. It is known to protect Gan (Liver) and Pi (Spleen) function, and may exert its antidepressant effects by regulating hippocampal neuroplasticity. In this review, we have summarized the association between depression and aberrant hippocampal neuroplasticity. Furthermore, we have discussed the researches published in the last 30 years on the effects of XYS on hippocampal neuroplasticity in order to elucidate the possible mechanisms underlying its therapeutic action against depression. The results of this review can aid future research on XYS for the treatment of depression.


Asunto(s)
Antidepresivos , Medicamentos Herbarios Chinos , Hipocampo , Plasticidad Neuronal , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Plasticidad Neuronal/efectos de los fármacos , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Animales , Depresión/tratamiento farmacológico , Depresión/fisiopatología , Medicina Tradicional China
15.
Nat Commun ; 15(1): 3820, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744833

RESUMEN

Lead (Pb2+) toxification is a concerning, unaddressed global public health crisis that leads to 1 million deaths annually. Yet, public policies to address this issue have fallen short. This work harnesses the unique abilities of crown ethers, which selectively bind to specific ions. This study demonstrates the synergistic integration of highly-scalable silicon photonics, with crown ether amine conjugation via Fischer esterification in an environmentally-friendly fashion. This realizes an integrated photonic platform that enables the in-operando, highly-selective and quantitative detection of various ions. The development dispels the existing notion that Fischer esterification is restricted to organic compounds, facilitating the subsequent amine conjugation for various crown ethers. The presented platform is specifically engineered for selective Pb2+ detection, demonstrating a large dynamic detection range, and applicability to field samples. The compatibility of this platform with cost-effective manufacturing indicates the potential for pervasive implementation of the integrated photonic sensor technology to safeguard against societal Pb2+ poisoning.

16.
Int J Antimicrob Agents ; 64(2): 107223, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38810940

RESUMEN

OBJECTIVES: Mycobacterium abscessus is a non-tuberculous mycobacterial pathogen that causes pulmonary and skin infections globally. Clarithromycin plays a pivotal role in treating M. abscessus infections, with resistance often leading to treatment failure. While canonical mutations in the 23S rRNA residue 2270/2271 are recognized as the primary mechanism for acquired clarithromycin resistance, resistant isolates lacking these mutations have been widely reported. This study aims to identify new mechanisms of clarithromycin resistance in M. abscessus. METHODS: We selected spontaneous resistant mutants derived from two parental strains characterized by erm(41) T28 and C28 sequevars, respectively. Whole-genome sequencing was performed on mutants lacking the 23S rRNA 2270/2271 mutations. Site-directed mutagenesis was used to confirm the resistance phenotypes of newly identified mutations. Bioinformatic analysis of publicly available genomes was conducted to evaluate the presence of these mutations in clinical isolates. The spatial localization of these mutations in the ribosome was analyzed to investigate potential mechanisms of resistance. RESULTS: A total of 135 resistant mutants were selected from the parental strains. Sequencing of the 78 mutants lacking the 23S rRNA 2270/2271 mutations identified mutations within the peptidyl-transferase center and hairpin loops 35, 49, and 74 of the 23S rRNA. These noncanonical mutations were identified in 57 of 1875 genomes of clinical isolates. Thirteen representative mutations were introduced into the bacterial genome, and their contributions to macrolide resistance were confirmed. The newly identified mutations all localized at the entrance of the nascent peptide exit tunnel, potentially contributing to resistance by disrupting the macrolide binding pocket. CONCLUSION: Several noncanonical 23S rRNA mutations conferring clarithromycin resistance were identified. These mutations enhance our understanding of macrolide resistance in M. abscessus and could serve as important markers for diagnosing clarithromycin resistance.


Asunto(s)
Antibacterianos , Claritromicina , Farmacorresistencia Bacteriana , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium abscessus , ARN Ribosómico 23S , Ribosomas , Claritromicina/farmacología , Mycobacterium abscessus/genética , Mycobacterium abscessus/efectos de los fármacos , ARN Ribosómico 23S/genética , Farmacorresistencia Bacteriana/genética , Antibacterianos/farmacología , Ribosomas/efectos de los fármacos , Ribosomas/genética , Ribosomas/metabolismo , Humanos , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Secuenciación Completa del Genoma , Mutagénesis Sitio-Dirigida
17.
Adv Sci (Weinh) ; 11(22): e2400336, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38605606

RESUMEN

The practical application of aqueous Zn-ion batteries (AZIBs) is hindered by the crazy Zn dendrites growth and the H2O-induced side reactions, which rapidly consume the Zn anode and H2O molecules, especially under the lean electrolyte and Zn anode. Herein, a natural disaccharide, d-trehalose (DT), is exploited as a novel multifunctional co-solvent to address the above issues. Molecular dynamics simulations and spectral characterizations demonstrate that DT with abundant polar -OH groups can form strong interactions with Zn2+ ions and H2O molecules, and thus massively reconstruct the coordination structure of Zn2+ ions and the hydrogen bonding network of the electrolyte. Especially, the strong H-bonds between DT and H2O molecules can not only effectively suppress the H2O activity but also prevent the rearrangement of H2O molecules at low temperature. Consequently, the AZIBs using DT30 electrolyte can show high cycling stability even under lean electrolyte (E/C ratio = 2.95 µL mAh-1), low N/P ratio (3.4), and low temperature (-12 °C). As a proof-of-concept, a Zn||LiFePO4 pack with LiFePO4 loading as high as 506.49 mg can be achieved. Therefore, DT as an eco-friendly multifunctional co-solvent provides a sustainable and effective strategy for the practical application of AZIBs.

18.
J Phys Condens Matter ; 36(25)2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38457831

RESUMEN

Cyclo-pentazolate salts (CPSs) as a new type of high-energy-density materials (HEDMs) with high nitrogen content have attracted considerable research attention. In contrast to the extensive studies on their energy properties, the thermal transport process in CPSs has been less studied which relates closely to the thermal safety of this material. Concerning the hydrazinium cyclo-pentazolate (HCP), we conduct a computational study to estimate the thermal conductivity of HCP by means of the non-equilibrium molecular dynamics (NEMD) simulation. To achieve that, we have customized interaction parameters based on the default OPLS force field for the HCP, as benchmarked by its crystal structure. Our simulations have revealed surprisingly anisotropic thermal conductivity for the HCP, while the thermal conductivity becomes highest roughly in the direction perpendicular tocyclo-N5-with its value notably higher than common high explosives. By modulating the interaction parameters within the HCP molecule, we have further captured a dominant role of the interaction betweencyclo-N5-in regulating the thermal conductivity of the HCP. The attractive Lennard-Jones (LJ) potential may restrict the relative motion betweencyclo-N5-, which forms a long-range order thus enhances thermal transport in the direction perpendicular tocyclo-N5-. Our simulations result on the effect of (cyclo-N5-)-(cyclo-N5-) interaction provide insights to engineer thermal transport in CPSs at the molecular level.

19.
Sci Data ; 11(1): 280, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459039

RESUMEN

The flower thrips Frankliniella intonsa (Thysanoptera: Thripidae) is a common insect found in flowers of many plants. Sometimes, F. intonsa causes damage to crops through direct feeding and transmission of plant viruses. Here, we assembled a chromosomal level genome of F. intonsa using the Illumina, Oxford Nanopore (ONT), and Hi-C technologies. The assembled genome had a size of 209.09 Mb, with a contig N50 of 997 bp, scaffold N50 of 13.415 Mb, and BUSCO completeness of 92.5%. The assembled contigs were anchored on 15 chromosomes. A set of 14,109 protein-coding genes were annotated in the genome with a BUSCO completeness of 95.0%. The genome contained 491 non-coding RNA and 0.57% of interspersed repeats. This high-quality genome provides a valuable resource for understanding the ecology, genetics, and evolution of F. intonsa, as well as for controlling thrips pests.


Asunto(s)
Genoma de los Insectos , Thysanoptera , Animales , Cromosomas , Flores , Thysanoptera/genética
20.
Parasites Hosts Dis ; 62(1): 53-63, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38443770

RESUMEN

The intracellular parasite Babesia microti is among the most significant species causing human babesiosis and is an emerging threat to human health worldwide. Unravelling the pathogenic molecular mechanisms of babesiosis is crucial in developing new diagnostic and preventive methods. This study assessed how priming with B. microti surface antigen 1 (BHSA 1) and seroreactive antigen 5-1-1 (BHSA 5-1-1) mediate protection against B. microti infection. The results showed that 500 µg/ml rBMSA1 and rBMSA5-1-1 partially inhibited the invasion of B. microti in vitro by 42.0 ± 3.0%, and 48.0 ± 2.1%, respectively. Blood smears revealed that peak infection at 7 days post-infection (dpi) was 19.6%, 24.7%, and 46.7% in the rBMSA1, rBmSA5-1-1, compared to the control groups (healthy mice infected with B. microti only), respectively. Routine blood tests showed higher white blood cell, red blood cell counts, and haemoglobin levels in the 2 groups (BMSA1 and BMSA5 5-1-1) than in the infection control group at 0-28 dpi. Moreover, the 2 groups had higher serum interferon-γ, tumor necrosis factor-α and Interleukin-17A levels, and lower IL-10 levels than the infection control group throughout the study. These 2 potential vaccine candidate proteins partially inhibit in vitro and in vivo B. microti infection and enhance host immunological response against B. microti infection.


Asunto(s)
Babesia microti , Babesiosis , Gastrópodos , Humanos , Animales , Ratones , Antígenos de Superficie , Grupos Control , Recuento de Eritrocitos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...