Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.758
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-38703990

RESUMO

Heated effluent injection, cold hypolimnetic water inputs from dams, and extreme weather events can lead to unpredictable temperature fluctuations in natural waters, impacting fish performance and fitness. We hypothesized that fish exposed to such unpredictable fluctuations would exhibit weaker growth and enhanced thermal tolerance compared to predictable conditions. Qingbo (Spinibarbus sinensis) was selected as the experimental subject in this study. The qingbo were divided into a constant temperature group (C, 22 ± 0.5 °C), a predictable temperature fluctuation group (PF, 22 ± 4 °C, first warming, then cooling within a day) and an unpredictable temperature fluctuation group (UF, 22 ± 4 °C, the order of warming or cooling is random). After 40 days of temperature acclimation, the growth, metabolic rate, spontaneous activity, thermal tolerance, plasma cortisol concentration and liver hsp70 level of the fish were measured. Unexpectedly, neither the PF nor the UF group showed decreased growth compared to the C group. This could be attributed to the fact that temperature variation did not lead to a substantial increase in basic energy expenditure. Furthermore, feeding rates increased due to temperature fluctuations, although the difference was not significant. Both the PF and UF groups exhibited increased upper thermal tolerance, but only the UF group exhibited improved lower thermal tolerance and higher liver hsp70 levels compared to the C group. The qingbo that experienced unpredictable temperature fluctuations had the best thermal tolerance among the 3 groups, which might have occurred because they had the highest level of hsp70 expression. This may safeguard fish against the potential lethal consequences of extreme temperatures in the future. These findings suggested that qingbo exhibited excellent adaptability to both predictable and unpredictable temperature fluctuations, which may be associated with frequent temperature fluctuations in its natural habitat.

2.
J Environ Manage ; 360: 121097, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38733844

RESUMO

With high-frequency data of nitrate (NO3-N) concentrations in waters becoming increasingly important for understanding of watershed system behaviors and ecosystem managements, the accurate and economic acquisition of high-frequency NO3-N concentration data has become a key point. This study attempted to use coupled deep learning neural networks and routine monitored data to predict hourly NO3-N concentrations in a river. The hourly NO3-N concentration at the outlet of the Oyster River watershed in New Hampshire, USA, was predicted through neural networks with a hybrid model architecture coupling the Convolutional Neural Networks and the Long Short-Term Memory model (CNN-LSTM). The routine monitored data (the river depth, water temperature, air temperature, precipitation, specific conductivity, pH and dissolved oxygen concentrations) for model training were collected from a nested high-frequency monitoring network, while the high-frequency NO3-N concentration data obtained at the outlet were not included as inputs. The whole dataset was separated into training, validation, and testing processes according to the ratio of 5:3:2, respectively. The hybrid CNN-LSTM model with different input lengths (1d, 3d, 7d, 15d, 30d) displayed comparable even better performance than other studies with lower frequencies, showing mean values of the Nash-Sutcliffe Efficiency 0.60-0.83. Models with shorter input lengths demonstrated both the higher modeling accuracy and stability. The water level, water temperature and pH values at monitoring sites were main controlling factors for forecasting performances. This study provided a new insight of using deep learning networks with a coupled architecture and routine monitored data for high-frequency riverine NO3-N concentration forecasting and suggestions about strategies about variable and input length selection during preprocessing of input data.

3.
Gastrointest Endosc ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734256

RESUMO

BACKGROUND AND AIM: After endoscopic full-thickness resection (EFTR), defects require a reliable and sustained closure. We present a novel, through-the-scope "bow-tie" (TTS-BT) closing device enabling direct defect closure without scope withdrawal. This preclinical study aimed to evaluate the feasibility and safety of this device for large defect closure after EFTR in a porcine model. METHODS: Exposed EFTR was performed for virtual lesions > 2 cm in the stomach of twelve pigs. Subsequently, TTS-BT closing devices were used for defect closure. Conventional metal clips were used to close any remaining defects. Gastroscopy was performed for 8 weeks to examine the wound sites and the pigs were subsequently sacrificed. After sacrificing the pigs, the wound healing was histologically verified by hematoxylin-eosin (HE) staining. The primary outcome was a successful closure rate, while the secondary outcomes were complete healing rate, closure time, and incidence of adverse events. RESULTS: The median long and short diameters of perforations were 4.0 (3.0-6.0) cm and 3.0 (2.0-4.0) cm, respectively. Defect closure using novel TTS-BT closure devices and conventional metal clips was successfully performed in all pigs. Complete healing was achieved in the defects of 12 pigs. The median closure time was 13 (9-38) minutes. No serious adverse events occurred during the 8-week follow-up. CONCLUSIONS: The novel TTS-BT closure device is feasible and safe for closing large gastric perforations and could be a promising tool for clinical practice.

4.
Sci Rep ; 14(1): 10471, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714840

RESUMO

Lung diseases globally impose a significant pathological burden and mortality rate, particularly the differential diagnosis between adenocarcinoma, squamous cell carcinoma, and small cell lung carcinoma, which is paramount in determining optimal treatment strategies and improving clinical prognoses. Faced with the challenge of improving diagnostic precision and stability, this study has developed an innovative deep learning-based model. This model employs a Feature Pyramid Network (FPN) and Squeeze-and-Excitation (SE) modules combined with a Residual Network (ResNet18), to enhance the processing capabilities for complex images and conduct multi-scale analysis of each channel's importance in classifying lung cancer. Moreover, the performance of the model is further enhanced by employing knowledge distillation from larger teacher models to more compact student models. Subjected to rigorous five-fold cross-validation, our model outperforms existing models on all performance metrics, exhibiting exceptional diagnostic accuracy. Ablation studies on various model components have verified that each addition effectively improves model performance, achieving an average accuracy of 98.84% and a Matthews Correlation Coefficient (MCC) of 98.83%. Collectively, the results indicate that our model significantly improves the accuracy of disease diagnosis, providing physicians with more precise clinical decision-making support.


Assuntos
Aprendizado Profundo , Neoplasias Pulmonares , Redes Neurais de Computação , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/classificação , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/classificação , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Adenocarcinoma/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/classificação , Processamento de Imagem Assistida por Computador/métodos , Diagnóstico Diferencial
5.
Res Sq ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38746123

RESUMO

Background Missouri is one of seven priority states identified by the Ending the HIV Epidemic Initiative, and St. Louis contains almost half of the people living with HIV (PLWH) in Missouri. As St. Louis has a marked history of structural racism and economic inequities, we utilized the Intersectionality Based Policy Analysis (IBPA) framework to guide a participatory needs assessment for planning and program development. Methods The planning team included researchers, the lead implementer from our community partner, and two community representatives, and had biweekly 60-90 minute meetings for 18 months. The planning team discussed and approved all research materials, reviewed and interpreted results, and made decisions about outreach, recruitment, conduct of the needs assessment and development of the planned intervention. The needs assessment integrated information from existing data, (1) interviews with (a) PLWH (n=12), (b) community leaders (n=5), (c) clinical leaders (n=4), and (d) community health workers (CHWs) (n=3) and (e) CHW supervisors (n=3) who participated in a Boston University-led demonstration project on CHWs in the context of HIV and (2) focus groups (2 FG, 12 participants) with front line health workers such as peer specialists, health coaches and outreach workers. A rapid qualitative analysis approach was used for all interviews and focus groups. Results The IBPA was used to guide team discussions of team values, definition and framing of the problem, questions and topics in the key informant interviews, and implementation strategies. Applying the IBPA framework contributed to a focus on intersectional drivers of inequities in HIV services. The effective management of HIV faces significant challenges from high provider turnover, insufficient integration of CHWs into care teams, and organizational limitations in tailoring treatment plans. Increasing use of CHWs for HIV treatment and prevention also faces challenges. People living with HIV (PLWH) encounter multiple barriers such as stigma, lack of social support, co-morbidities, medication side effects and difficulties in meeting basic needs. Conclusions Addressing intersectional drivers of health inequities may require multi-level, structural approaches. We see the IBPA as a valuable tool for participatory planning while integrating community engagement principles in program and implementation design for improving HIV outcomes.

6.
RSC Adv ; 14(22): 15619-15626, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38746833

RESUMO

Solar-powered sorption-based atmospheric water harvesting (AWH) technology is a promising solution to the freshwater scarcity in arid regions. Existing adsorbent materials still face challenges in aspects such as cycling stability and adsorption kinetics and require further development. Herein, we presented a strategy for the in situ fabrication of high-performance adsorbents, lithium chloride (LiCl)-decorated metal-organic framework (MOF)-derived porous carbon sorbents (PCl), via high-temperature pyrolysis and hydrogen chloride (HCl) vapor treatment. The sorbents display high adsorption capacity across a wide range of humidity water adsorption capacities in a wide humidity range with the maximum adsorption capacity of 7.87 g g-1, and rapid response to the solar-driven process and excellent cyclic stability. The LiCl nanocrystals in PCl can be utilized efficiently and decorated within the porous framework stably, and demonstrate water adsorption at 20%, 40%, 60% and 80% RH, of 1.34, 1.69, 2.56 and 4.23 gH2O·gLiCl-1, respectively, and significantly higher water uptake and release rates than bulk LiCl. This may provide new guides for designing efficient solar-driven AWH.

7.
Mol Cell Biochem ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748384

RESUMO

Axis inhibitor protein 1 (AXIN1) is a protein recognized for inhibiting tumor growth and is commonly involved in cancer development. In this study, we explored the potential molecular mechanisms that connect alternative splicing of AXIN1 to the metastasis of hepatocellular carcinoma (HCC). Transcriptome sequencing, RT‒PCR, qPCR and Western blotting were utilized to determine the expression levels of AXIN1 in human HCC tissues and HCC cells. The effects of the AXIN1 exon 9 alternative splice isoform and SRSF9 on the migration and invasion of HCC cells were assessed through wound healing and Transwell assays, respectively. The interaction between SRSF9 and AXIN1 was investigated using UV crosslink RNA immunoprecipitation, RNA pulldown, and RNA immunoprecipitation assays. Furthermore, the involvement of the AXIN1 isoform and SRSF9 in HCC metastasis was validated in a nude mouse model. AXIN1-L (exon 9 including) expression was downregulated, while AXIN1-S (exon 9 skipping) was upregulated in HCC. SRSF9 promotes the production of AXIN1-S by interacting with the sequence of exons 8 and 10 of AXIN1. AXIN1-S significantly promoted HCC cells migration and invasion by activating the Wnt pathway, while the opposite effects were observed for AXIN1-L. In vivo experiments demonstrated that AXIN1-L inhibited HCC metastasis, whereas SRSF9 promoted HCC metastasis in part by regulating the level of AXIN1-S. AXIN1, a tumor suppressor protein that targets the AXIN1/Wnt/ß-catenin signaling axis, may be a promising prognostic factor and a valuable therapeutic target for HCC.

8.
Curr Res Food Sci ; 8: 100734, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38708102

RESUMO

This study evaluated the effect of heat treatment on the conversion of ginsenoside and the ameliorative effect of heat-treated total ginsenoside (HG) from fresh ginseng on cyclophosphamide (CTX)-induced liver injury. LC-MS analysis revealed that the content of rare ginsenosides increased markedly after heat treatment. HG significantly attenuated CTX-induced hepatic histopathological injury in mice. Western blotting analysis showed that untreated total ginsenoside (UG) and HG regulated the Nrf2/HO-1 and TLR4/MAPK pathways. Importantly, these results may be relevant to the modulation of the intestinal flora. UG and HG significantly increased the short-chain fatty acids (SCFAs)-producing bacteria Lactobacillus and reduced the LPS-producing bacteria Bacteroides and Parabacteroides. These changes in intestinal flora affected the levels of TNF-α, LPS and SCFAs. In short, UG and HG alleviated CTX-induced liver injury by regulating the intestinal flora and the LPS-TLR4-MAPK pathway, and HG was more effective. HG has the potential to be a functional food that can alleviate chemical liver injury.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38713183

RESUMO

The microstructured superhydrophobic surface serves as an alternative strategy to decrease resistance of underwater vehicles, but the sustainment of an entrapped air layer and the stability of the corresponding gas-liquid interface within textures in flow shear or high pressure are still a great challenge. Inspired by the scales of Parantica melaneus wings, we propose a biomimetic surface with a hierarchical structure featuring longitudinal ridges and regular cavities that firmly pin the gas-liquid interface. The drag reduction rate of the Butterfly Wing Scale-Like Surface (BWSLS) demonstrates a noticeable rise over the single-scale textured mainstream biomimetic surfaces at moderate Reynolds numbers. The superior drag reduction mechanism is revealed as the synergistic effect of a thicker gas film and a more pronounced secondary vortex within the hierarchical textures. The former reduces the velocity gradient near the surface, while the latter decreases the vorticity and energy dissipation. In a high hydrostatic pressure environment, the proposed surface also demonstrates significant stability of the gas-liquid interface, with a gas coverage rate of over 67% during the cyclic loading, surpassing single-structured surfaces. Our study suggests promising surface designs for optimal drag reduction by mimicking and leveraging diverse surfaces of organisms adapted to oceanic climates.

10.
J Neurol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717610

RESUMO

OBJECTIVE: To determine the efficacy and safety of perampanel (PER) as an adjunctive therapy in children aged 4-12 years with epilepsy. METHODS: We performed a non-randomized, open-label, placebo-uncontrolled, real-world self-controlled study that included 216 young children (aged 4-12 years) with epilepsy who received PER as adjunctive therapy at the children's hospital affiliated with Chongqing Medical University from July 4, 2020, to September 20, 2023. RESULTS: (1) The efficacy rates of adjunctive PER therapy at 3, 6, 9, and 12 months were 62.8%, 67.8%, 65.3%, and 61.2%, respectively. PER showed efficacy in alleviating focal seizures, generalized tonic-clonic seizures, myoclonic seizures, and absence seizures. The efficacy rates for variants of self-limited epilepsy with centrotemporal spikes (SeLECTS) and Lennox-Gastaut syndrome (LGS) were 89.5% and 66.7%, respectively. (2) Focal non-motor onset seizures with or without impaired awareness, focal to bilateral tonic-clonic seizures (FBTCS), LGS, variants of SeLECTS, the number of concomitant antiseizure medications (ASMs), a family history of epilepsy, and focal lesions on cranial magnetic resonance imaging were independent factors affecting efficacy. The order of PER addition did not affect efficacy. The retention rates at 3, 6, 9, and 12 months were 90.7%, 84.7%, 74.7%, 64.9%, respectively. (3) Adverse reactions occurred in 45 patients (45/216, 20.8%), with irritability/aggressive behavior (18/216, 8.3%) and somnolence (14/216, 6.5%) being the most common. Twelve patients (12/216, 5.6%) withdrew from the study because of adverse reactions. CONCLUSION: In young Chinese children with epilepsy, PER is effective, safe, and well-tolerated as an adjunctive therapy, making it a viable option for use with broad-spectrum ASMs.

11.
Am J Reprod Immunol ; 91(5): e13839, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38695218

RESUMO

BACKGROUND AND AIMS: There is clinical disagreement on whether to treat hyperprolactinemia with medication before embryo transfer. The aim of this study is to identify the impact of basal prolactin (PRL) levels on pregnancy outcomes in fresh embryo transfer cycles. METHODS: This retrospective study involved 2,648 women who underwent basal PRL level testing and fresh embryo transfer between January 2015 and December 2020 at our Hospital's Department of Assisted Reproduction. Basal PRL levels can be classified into three categories: <30 (n = 2339), 30­60 (n = 255), and ≥60 (n = 54) µg/l. Pregnancy outcome was defined as the primary outcome measure, and the live birth rate was defined as the second outcome measure. Subsequently, univariate and multivariable logistic regression analysis was used to reveal the association between basal PRL levels and pregnancy outcomes after considering several potential confounding factors. RESULTS: Elevated basal PRL levels were found not a risk factor for pregnancy outcomes in patients receiving good-quality embryo transfer (p > .05). For pregnancy or not, female age (OR: 1.03; 95% CI: 1.01-1.05), embryos transferred (OR: 0.52; 95% CI: 0.41-0.65), and normal fertilization rate (OR: 0.68; 95% CI: 0.48-0.97) were found to be an independent risk factor. For ongoing pregnancy or not, female age (OR: 1.07; 95% CI: 1.03-1.11), embryos transferred (OR: 0.57; 95% CI: 0.37-0.88), and menstrual cycle (OR: 1.76; 95% CI: 1.22-2.54) were also independent risk factors. CONCLUSION: There is no adverse impact on pregnancy outcomes during embryo transfer cycles with good-quality embryos when PRL levels are elevated.


Assuntos
Transferência Embrionária , Resultado da Gravidez , Prolactina , Humanos , Feminino , Gravidez , Prolactina/sangue , Adulto , Estudos Retrospectivos , Fertilização in vitro , Taxa de Gravidez
12.
Parasit Vectors ; 17(1): 192, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654385

RESUMO

BACKGROUND: Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological impairments. Developing effective neuroprotective drugs to improve the quality of life in affected individuals is critical. METHODS: We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT-qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice's energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration. RESULTS: Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex. CONCLUSIONS: Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection.


Assuntos
Angiostrongylus cantonensis , Metabolismo Energético , Hormônios Hipotalâmicos , Melaninas , Hormônios Hipofisários , Infecções por Strongylida , Animais , Feminino , Masculino , Camundongos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/parasitologia , Encéfalo/patologia , Hormônios Hipotalâmicos/metabolismo , Hormônios Hipotalâmicos/farmacologia , Melaninas/metabolismo , Melaninas/farmacologia , Hormônios Hipofisários/metabolismo , Hormônios Hipofisários/farmacologia , Infecções por Strongylida/patologia
13.
J Surg Educ ; 81(6): 794-803, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38664171

RESUMO

OBJECTIVE: Leadership is an essential skill for surgeons, but it is not systematically taught in residency. The objective of this study was to explore the current experiences, motivators, and perspectives on leadership training of general surgery residents. DESIGN/SETTING/PARTICIPANTS: Semi-structured focus groups were conducted with 20 general surgery residents at an academic training program. Six in-person sessions (one for each postgraduate year and research) were recorded, transcribed, and de-identified. Data were inductively coded by 2 independent researchers and analyzed thematically. Discrepancies were discussed and resolved through consensus. RESULTS: Participants described developing their leadership skills prior to residency through formal (e.g., job and military) and informal (e.g., extracurricular) experiences. Most reported that leadership development during residency occurred informally (e.g., emulating mentors, trial-and-error). Evolving responsibilities and expectations shaped residents' leadership values: junior residents focused on student and task management and adaptation to new teams; mid-level residents emphasized emotional intelligence and delivery of resident feedback; and senior residents stressed team engagement, inspiring the team, and teaching/mentoring. Major transition periods between residency levels were identified as critical times for leadership training as they allow for self-reflection, motivating residents to participate in a leadership curriculum. Employing level appropriate and immediately applicable content during this time would encourage curriculum attendance and prepare residents for new roles. CONCLUSIONS: There is a lack of formal leadership training in general surgery residency. There is an opportunity to design and implement leadership training that engages surgical residents with level-relevant content and strategies. Transition periods offer optimal timing for maximal curricula uptake.


Assuntos
Grupos Focais , Cirurgia Geral , Internato e Residência , Liderança , Pesquisa Qualitativa , Humanos , Cirurgia Geral/educação , Feminino , Masculino , Adulto , Currículo , Educação de Pós-Graduação em Medicina/métodos
14.
Front Neurol ; 15: 1292587, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628701

RESUMO

Purpose: This bibliometric study explores cerebral palsy (CP) research from 2003 to 2022 to reveal the topic hotspots and collaborations. Methods: We retrieved studies on CP from the Web of Science Core Collection from 2003 to 2022 and then used CiteSpace and Bibliometrix to perform a bibliometric analysis and attain knowledge mapping, including publication outputs, funding, journals, authors, institutions, countries/territories, keywords, collaborative relationships, and topic hotspots. Results: In total, 8,223 articles were published from 2003 to 2022. During this period, the number of publications increased continuously. Developmental Medicine and Child Neurology was the most productive and frequently co-cited journal. Boyd was the most productive and influential author, with 143 publications and 4,011 citations. The United States and Vrije Universiteit Amsterdam were the most productive countries and institutions, respectively. Researchers and institutions from the USA, Australia, and Canada constituted the core research forces, with extensive collaborations worldwide. The most common keywords were gait (553), rehabilitation (440), spasticity (325), botulinum toxin (174), therapy (148), upper extremity (141), quality of life (140), disability (115), pain (98), electromyography (97), kinematics (90), balance (88), participation (85), and walking (79). Conclusion: This study provides a systematic and comprehensive analysis of the CP-related literature. It reveals that Developmental Medicine and Child Neurology is the most active journal in this field. The USA, Vrije Universiteit Amsterdam, and Boyd are the top countries, institutions, and authors, respectively. Emerging treatment methods, complication management, and functional recovery comprise the future research directions and potential topic hotspots for CP.

15.
Nat Commun ; 15(1): 3304, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632242

RESUMO

Defect scattering is well known to suppress thermal transport. In this study, however, we perform both molecular dynamics and Boltzmann transport equation calculations, to demonstrate that introducing defect scattering in nanoscale heating zone could surprisingly enhance thermal conductance of the system by up to 75%. We further reveal that the heating zone without defects yields directional nonequilibrium with overpopulated oblique-propagating phonons which suppress thermal transport, while introducing defects redirect phonons randomly to restore directional equilibrium, thereby enhancing thermal conductance. We demonstrate that defect scattering can enable such thermal transport enhancement in a wide range of temperatures, materials, and sizes, and offer an unconventional strategy for enhancing thermal transport via the manipulation of phonon directional nonequilibrium.

16.
DNA Res ; 31(3)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38590243

RESUMO

Calophaca sinica is a rare plant endemic to northern China which belongs to the Fabaceae family and possesses rich nutritional value. To support the preservation of the genetic resources of this plant, we have successfully generated a high-quality genome of C. sinica (1.06 Gb). Notably, transposable elements (TEs) constituted ~73% of the genome, with long terminal repeat retrotransposons (LTR-RTs) dominating this group of elements (~54% of the genome). The average intron length of the C. sinica genome was noticeably longer than what has been observed for closely related species. The expansion of LTR-RTs and elongated introns emerged had the largest influence on the enlarged genome size of C. sinica in comparison to other Fabaceae species. The proliferation of TEs could be explained by certain modes of gene duplication, namely, whole genome duplication (WGD) and dispersed duplication (DSD). Gene family expansion, which was found to enhance genes associated with metabolism, genetic maintenance, and environmental stress resistance, was a result of transposed duplicated genes (TRD) and WGD. The presented genomic analysis sheds light on the genetic architecture of C. sinica, as well as provides a starting point for future evolutionary biology, ecology, and functional genomics studies centred around C. sinica and closely related species.


Assuntos
Genoma de Planta , Retroelementos , Fabaceae/genética , Cromossomos de Plantas , Duplicação Gênica , Tamanho do Genoma , Elementos de DNA Transponíveis , Evolução Molecular , Sequências Repetidas Terminais , Genômica , Íntrons , Filogenia
17.
Eur J Med Chem ; 271: 116399, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38640868

RESUMO

The structural optimization of B14, an antibacterial agent we previously obtained, has led to the discovery of a new class of CH2-linked quinolone-aminopyrimidine hybrids with potent anti-MRSA activities. Surprisingly, the hybrids lacking a C-6 fluoro atom at the quinolone nucleus showed equal or even stronger anti-MRSA activities than their corresponding 6-fluoro counterparts, despite the well-established structure-activity relationships (SARs) indicating that the 6-fluoro substituent enhances the antibacterial activity in conventional fluoroquinolone antibiotics. Moreover, these new hybrids, albeit structurally related to conventional fluoroquinolones, showed no cross-resistance with fluoroquinolone drugs. The most active compound, 15m, exhibited excellent activities with a MIC value of 0.39 µg/mL against both fluoroquinolone-sensitive strain USA500 and -resistant MRSA isolate Mu50. Further resistance development studies indicated MRSA is unlikely to acquire resistance against 15m. Moreover, 15m displayed favorable in vivo half-life and safety profiles. These findings suggest a rationale for further evolution of quinolone antibiotics with a high barrier to resistance.


Assuntos
Antibacterianos , Fluoroquinolonas , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Pirimidinas , Quinolonas , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Relação Estrutura-Atividade , Pirimidinas/farmacologia , Pirimidinas/química , Pirimidinas/síntese química , Fluoroquinolonas/farmacologia , Fluoroquinolonas/química , Fluoroquinolonas/síntese química , Quinolonas/farmacologia , Quinolonas/química , Quinolonas/síntese química , Estrutura Molecular , Farmacorresistência Bacteriana/efeitos dos fármacos , Relação Dose-Resposta a Droga , Animais , Humanos
18.
Heliyon ; 10(8): e29481, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38655332

RESUMO

Addressing the treatment of depression is crucial; nevertheless, the etiology and pathogenesis remain unelucidated. Therefore, this study investigated the effects of teriflunomide (TF) on corticosterone (CORT)-induced depression-like behaviors in mice. Notably, TF administration resulted in a substantial amelioration of anxiety and depression-like behaviors observed in CORT-treated mice. This was evidenced by behavioral assessments conducted via the sucrose preference test (SPT), open-field test (OFT), novelty-suppressed feeding test (NSFT), forced swimming test (FST), and tail suspension test (TST). The administration of CORT inflicts damage upon oligodendrocytes and neurons within the hippocampus. Our findings indicate that TF offers significant protective effects on oligodendrocytes, mitigating apoptosis both invivo and invitro. Additionally, TF was found to counteract the CORT-induced neuronal loss and synaptic damage, as demonstrated by an increase in Nissl-positive cells across hippocampal regions CA1, CA3, and the dentate gyrus (DG) alongside elevated levels of synapse-related proteins including PSD-95 and synaptophysin. Additionally, TF treatment facilitated a reduction in the levels of apoptosis-related proteins while simultaneously augmenting the levels of Bcl2. Our findings indicate that TF administration effectively mitigates CORT-induced depression-like behaviors and reverses damage to oligodendrocytes and neurons in the hippocampus, suggesting TF as a promising candidate for depression.

19.
Eur J Med Chem ; 270: 116392, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38608408

RESUMO

The emergence of serious bacterial resistance towards clinical oxacins poses a considerable threat to global public health, necessitating the development of novel structural antibacterial agents. Seven types of novel indolylacryloyl-derived oxacins (IDOs) were designed and synthesized for the first time from commercial 3,4-difluoroaniline via an eight-step procedure. The synthesized compounds were characterized by modern spectroscopic techniques. All target molecules were evaluated for antimicrobial activities. Most of the prepared IDOs showed a broad antibacterial spectrum and strong activities against the tested strains, especially ethoxycarbonyl IDO 10d (0.25-0.5 µg/mL) and hydroxyethyl IDO 10e (0.25-1 µg/mL) exhibited much superior antibacterial efficacies to reference drug norfloxacin. These highly active IDOs also displayed low hemolysis, cytotoxicity and resistance, as well as rapid bactericidal capacity. Further investigations indicated that ethoxycarbonyl IDO 10d and hydroxyethyl IDO 10e could effectively reduce the exopolysaccharide content and eradicate the formed biofilm, which might delay the development of drug resistance. Preliminary exploration of the antibacterial mechanism revealed that active IDOs could not only destroy membrane integrity, resulting in changes in membrane permeability, but also promote the accumulation of reactive oxygen species, leading to the production of malondialdehyde and decreased bacterial metabolism. Moreover, they exhibited the capability to bind with DNA and DNA gyrase, forming supramolecular complexes through various noncovalent interactions, thereby inhibiting DNA replication and causing bacterial death. All the above results suggested that the newly developed indolylacryloyl-derived oxacins should hold great promise as potential multitargeting broad-spectrum antibacterial candidates to overcome drug resistance.


Assuntos
Antibacterianos , Norfloxacino , Antibacterianos/farmacologia , Antibacterianos/química , Norfloxacino/farmacologia , Bactérias , Permeabilidade da Membrana Celular , DNA/farmacologia , Testes de Sensibilidade Microbiana
20.
Artigo em Inglês | MEDLINE | ID: mdl-38632199

RESUMO

Aluminum (Al) toxicity poses a significant challenge to agricultural productivity, particularly in acidic soils. The banana crop, predominantly cultivated in tropical and subtropical climates, often grapples with low pH and Al toxicity. This study seeks to explore the differential responses of two banana genotypes with varying Al tolerance (Baodao and Baxi) to Al exposure (100 and 500 µM) for 24 h. Microscopic analysis uncovered distinctive structural modifications in root cells, with Baodao displaying more severe alterations in response to Al stress. There was higher superoxide (O2-.) and hydrogen peroxide (H2O2) production and lipid peroxidation in Baodao indicating enhanced oxidative stress and membrane damage. Al accumulation in root tips was higher in Baxi than Baodao, while the roots of Baodao had a higher accumulation of callose. Nutrient content analysis revealed alterations in ion levels, highlighting the impact of Al exposure on nutrient uptake and homeostasis. In summary, Al differentially affects callose deposition, which, in turn, leads to Al uptake and nutrient homeostasis alteration in two contrasting banana genotypes. This intricate interplay is a key factor in understanding plant responses to aluminum toxicity and can inform strategies for crop improvement and soil management in aluminum-stressed environments.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA