Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 728
Filtrar
1.
Nature ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987600

RESUMO

Most of the state-of-the-art thermoelectric materials are inorganic semiconductors. Owing to the directional covalent bonding, they usually show limited plasticity at room temperature1,2, for example, with a tensile strain of less than five per cent. Here we discover that single-crystalline Mg3Bi2 shows a room-temperature tensile strain of up to 100 per cent when the tension is applied along the (0001) plane (that is, the ab plane). Such a value is at least one order of magnitude higher than that of traditional thermoelectric materials and outperforms many metals that crystallize in a similar structure. Experimentally, slip bands and dislocations are identified in the deformed Mg3Bi2, indicating the gliding of dislocations as the microscopic mechanism of plastic deformation. Analysis of chemical bonding reveals multiple planes with low slipping barrier energy, suggesting the existence of several slip systems in Mg3Bi2. In addition, continuous dynamic bonding during the slipping process prevents the cleavage of the atomic plane, thus sustaining a large plastic deformation. Importantly, the tellurium-doped single-crystalline Mg3Bi2 shows a power factor of about 55 microwatts per centimetre per kelvin squared and a figure of merit of about 0.65 at room temperature along the ab plane, which outperforms the existing ductile thermoelectric materials3,4.

2.
Int J Biol Macromol ; 276(Pt 1): 133781, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38992528

RESUMO

Peptide-major histocompatibility complex (pMHC) multimers are wide recognized as the premier technique for detecting, characterizing, and isolating antigen-specific CD8+ T-cell subsets. These multimers are specifically useful in studying infections, autoimmune conditions, and cancer through single-cell analysis techniques such as flow cytometry and fluorescence microscopy. However, the development of high-throughput assays with commercially available pMHC tetramers can be expensive, while in-house production may pose challenges for most biology research laboratories. In this context, we introduce a cost-friendly and uncomplicated protocol to prepare empty MHC class I tetramers using disulfide-stabilized molecules and photolabile peptide ligands. Our method relies on disulfide bond-stabilized MHC-I molecules, which demonstrated stability when folded into stable monomers in the presence of a photolabile epitope. These monomers, upon ultraviolet irradiation and streptavidin binding, efficiently assemble into tetramers devoid of any peptide. Following a short incubation with the peptide of interest under gentle conditions, the resulting pMHC tetramer effectively detects patient-sourced, neoantigen-specific T cells. Our unique approach streamlines large-scale pMHC generation, thus paving the way for advancements in T cell-based diagnostics and personalized therapies.

3.
World J Otorhinolaryngol Head Neck Surg ; 10(2): 113-120, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38855290

RESUMO

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

4.
Proc Natl Acad Sci U S A ; 121(27): e2409257121, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38917009

RESUMO

Dynamic protein structures are crucial for deciphering their diverse biological functions. Two-dimensional infrared (2DIR) spectroscopy stands as an ideal tool for tracing rapid conformational evolutions in proteins. However, linking spectral characteristics to dynamic structures poses a formidable challenge. Here, we present a pretrained machine learning model based on 2DIR spectra analysis. This model has learned signal features from approximately 204,300 spectra to establish a "spectrum-structure" correlation, thereby tracing the dynamic conformations of proteins. It excels in accurately predicting the dynamic content changes of various secondary structures and demonstrates universal transferability on real folding trajectories spanning timescales from microseconds to milliseconds. Beyond exceptional predictive performance, the model offers attention-based spectral explanations of dynamic conformational changes. Our 2DIR-based pretrained model is anticipated to provide unique insights into the dynamic structural information of proteins in their native environments.


Assuntos
Aprendizado de Máquina , Proteínas , Espectrofotometria Infravermelho , Proteínas/química , Espectrofotometria Infravermelho/métodos , Conformação Proteica , Dobramento de Proteína , Estrutura Secundária de Proteína
5.
Acta Trop ; 257: 107308, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945422

RESUMO

Dengue fever is a viral illness, mainly transmitted by Aedes aegypti and Aedes albopictus. With climate change and urbanisation, more urbanised areas are becoming suitable for the survival and reproduction of dengue vector, consequently are becoming suitable for dengue transmission in China. Chongqing, a metropolis in southwestern China, has recently been hit by imported and local dengue fever, experiencing its first local outbreak in 2019. However, the genetic evolution dynamics of dengue viruses and the spatiotemporal patterns of imported and local dengue cases have not yet been elucidated. Hence, this study implemented phylogenetic analyses using genomic data of dengue viruses in 2019 and 2023 and a spatiotemporal analysis of dengue cases collected from 2013 to 2022. We sequenced a total of 15 nucleotide sequences of E genes. The dengue viruses formed separate clusters and were genetically related to those from Guangdong Province, China, and countries in Southeast Asia, including Laos, Thailand, Myanmar and Cambodia. Chongqing experienced a dengue outbreak in 2019 when 168 imported and 1,243 local cases were reported, mainly in September and October. Few cases were reported in 2013-2018, and only six were imported from 2020 to 2022 due to the COVID-19 lockdowns. Our findings suggest that dengue prevention in Chongqing should focus on domestic and overseas population mobility, especially in the Yubei and Wanzhou districts, where airports and railway stations are located, and the period between August and October when dengue outbreaks occur in endemic regions. Moreover, continuous vector monitoring should be implemented, especially during August-October, which would be useful for controlling the Aedes mosquitoes. This study is significant for defining Chongqing's appropriate dengue prevention and control strategies.

6.
RSC Adv ; 14(26): 18317-18329, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38860244

RESUMO

Wound management remains a challenge in clinical practice. Nowadays, patients have an increasing demand for wound repair with enhanced speed and quality; therefore, there is a great need to seek therapeutic strategies that can promote rapid and effective wound healing. In this study, we developed a carboxymethyl cellulose hydrogel loaded with l-carnosine (CRN@hydrogel) for potential application as a wound dressing. In vitro experiments confirmed that CRN@hydrogel can release over 80% of the drug within 48 h and demonstrated its favorable cytocompatibility and blood compatibility, thus establishing its applicability for safe utilization in clinical practice. Using a rat model, we found that this hydrogel could promote and accelerate wound healing more effectively. These results indicate that the novel hydrogel can serve as an efficient therapeutic strategy for wound treatment.

7.
J Med Internet Res ; 26: e44443, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833294

RESUMO

BACKGROUND: Singapore, like the rest of Asia, faces persistent challenges to mental health promotion, including stigma around unwellness and seeking treatment and a lack of trained mental health personnel. The COVID-19 pandemic, which created a surge in mental health care needs and simultaneously accelerated the adoption of digital health solutions, revealed a new opportunity to quickly scale innovative solutions in the region. OBJECTIVE: In June 2020, the Singaporean government launched mindline.sg, an anonymous digital mental health resource website that has grown to include >500 curated local mental health resources, a clinically validated self-assessment tool for depression and anxiety, an artificial intelligence (AI) chatbot from Wysa designed to deliver digital therapeutic exercises, and a tailored version of the website for working adults called mindline at work. The goal of the platform is to empower Singapore residents to take charge of their own mental health and to be able to offer basic support to those around them through the ease and convenience of a barrier-free digital solution. METHODS: Website use is measured through click-level data analytics captured via Google Analytics and custom application programming interfaces, which in turn drive a customized analytics infrastructure based on the open-source platforms Titanium Database and Metabase. Unique, nonbounced (users that do not immediately navigate away from the site), engaged, and return users are reported. RESULTS: In the 2 years following launch (July 1, 2020, through June 30, 2022), the website received >447,000 visitors (approximately 15% of the target population of 3 million), 62.02% (277,727/447,783) of whom explored the site or engaged with resources (referred to as nonbounced visitors); 10.54% (29,271/277,727) of those nonbounced visitors returned. The most popular features on the platform were the dialogue-based therapeutic exercises delivered by the chatbot and the self-assessment tool, which were used by 25.54% (67,626/264,758) and 11.69% (32,469/277,727) of nonbounced visitors. On mindline at work, the rates of nonbounced visitors who engaged extensively (ie, spent ≥40 seconds exploring resources) and who returned were 51.56% (22,474/43,588) and 13.43% (5,853/43,588) over a year, respectively, compared to 30.9% (42,829/138,626) and 9.97% (13,822/138,626), respectively, on the generic mindline.sg site in the same year. CONCLUSIONS: The site has achieved desired reach and has seen a strong growth rate in the number of visitors, which required substantial and sustained digital marketing campaigns and strategic outreach partnerships. The site was careful to preserve anonymity, limiting the detail of analytics. The good levels of overall adoption encourage us to believe that mild to moderate mental health conditions and the social factors that underly them are amenable to digital interventions. While mindline.sg was primarily used in Singapore, we believe that similar solutions with local customization are widely and globally applicable.


Assuntos
COVID-19 , Saúde Mental , Autocuidado , Humanos , Singapura , Autocuidado/métodos , Telemedicina , Promoção da Saúde/métodos , Internet , Pandemias , Inteligência Artificial , SARS-CoV-2 , Serviços de Saúde Mental
8.
Artigo em Inglês | MEDLINE | ID: mdl-38702157

RESUMO

Introduction: Preeclampsia (PE) is a fundamental cause of preterm labor, intrauterine growth restriction, and persistent postpartum hypertension. In the present study, we aimed to investigate the correlation between 24-h urinary protein excretion, serum markers, and placental growth factor and their adverse pregnancy outcomes in patients with PE. Methods: A total of 126 pregnant women with PE (86 cases of mild PE and 40 cases of severe PE, assigned to the observation group) who came to our hospital from March 2019 to December 2021 for regular obstetric checkups and delivery were selected, with 60 healthy pregnant women assigned to the control group. Routine biochemical parameters, 24-h urinary protein quantification, serum parameters, and placental growth factor levels were recorded. The incidence of adverse neonatal pregnancy outcomes and abnormal fetal heart monitoring, neonatal body mass, 1 min Apgar score, and other adverse pregnancy outcomes were also analyzed in the different groups. Results: In comparison with healthy pregnant subjects, PE patients had earlier delivery gestational weeks (P < .05), significantly higher systolic blood pressure (SBP), diastolic blood pressure (DBP), 24-h urinary protein excretion, total cholesterol (TC), triglyceride (TG), D-Dimer and human chorionic gonadotropin (ß-hCG) levels (P < .05), lower albumin (ALB), platelet count, pregnant associated plasma protein A (PAPP-A) and placental growth factor (PLGF) (P < .05), and higher incidence of maternal and perinatal adverse outcomes (P < .05). Conclusions: Combined screening of 24-h urinary protein, PAPP-A, ß-hCG, PLGF, and serum indicators in early pregnancy are essential in predicting PE, allowing timely assessment of the risk of adverse pregnancy, and providing a basis for clinical intervention.

9.
Front Nutr ; 11: 1351797, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38751736

RESUMO

Background: AAA is a fatal condition that commonly occurs during vascular surgery. Nutritional status exerts a significant influence on the prognosis of various pathological conditions Scores from the CONUT screening tool have been shown to predict outcomes of certain malignancies and chronic diseases. However, the ramifications of nutritional status on AAA patients undergoing EVAR have not been elucidated in prior studies. In this study, we aimed to elucidate the correlation between CONUT scores and postoperative prognostic outcomes in patients with AAA undergoing EVAR. Methods: This was a retrospective review of 177 AAA patients treated with EVAR from June 2018 to November 2019 in a single center. Patient characteristics, CONUT scores, and postoperative status were collected. These patients were stratified into groups A and B according to CONUT scores. Subsequently, a comparative analysis of the baseline characteristics between the two cohorts was conducted. Cox proportional hazards and logistic regression analyses were employed to identify the autonomous predictors of mid-term mortality and complications, respectively. Results: Compared with group A, patients in group B had higher midterm mortality (p < 0.001). Univariate analysis showed that CONUT scores; respiratory diseases; stent types; preoperative Hb, CRP, PT, and Fb levels were risk factors for death. Multivariate analysis confirmed that CONUT score [HR, 1.276; 95% CI, 1.029-1.584; p = 0.027] was an independent risk factor for mortality. Logistic regression analysis showed that prior arterial disease, smoking, and D-dimer levels were risk factors, although multivariate analysis showed smoking (OR, 3.492; 95% CI, 1.426-8.553; p = 0.006) was an independent risk factor. Kaplan-Meier curves showed that patients in group B had shorter mid-term survival than those in group A (log-rank p < 0.001). Conclusion: Malnutrition was strongly associated with mid-term mortality in patients with infrarenal AAA treated with EVAR.

10.
Thorac Cancer ; 15(17): 1369-1384, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38720472

RESUMO

BACKGROUND: Solute carrier family 34 member 2 (SLC34A2) has been implicated in the development of various malignancies. However, the clinical significance and underlying molecular mechanisms of SLC34A2 in esophageal squamous cell carcinoma (ESCC) remain elusive. METHODS: Western blotting, quantitative real-time PCR and immunohistochemistry were utilized to evaluate the expression levels of SLC34A2 mRNA/protein in ESCC cell lines or tissues. Kaplan-Meier curves were employed for survival analysis. CCK-8, colony formation, EdU and xenograft tumor model assays were conducted to determine the impact of SLC34A2 on ESCC cell proliferation. Cell cycle was examined using flow cytometry. RNA-sequencing and enrichment analysis were carried out to explore the potential signaling pathways. The autophagic flux was evaluated by western blotting, mRFP-GFP-LC3 reporter system and transmission electron microscopy. Immunoprecipitation and mass spectrometry were utilized for identification of potential SLC34A2-interacting proteins. Cycloheximide (CHX) chase and ubiquitination assays were conducted to test the protein stability. RESULTS: The expression of SLC34A2 was significantly upregulated in ESCC and correlated with unfavorable clinicopathologic characteristics particularly the Ki-67 labeling index and poor prognosis of ESCC patients. Overexpression of SLC34A2 promoted ESCC cell proliferation, while silencing SLC34A2 had the opposite effect. Moreover, SLC34A2 induced autophagy to promote ESCC cell proliferation, whereas inhibition of autophagy suppressed the proliferation of ESCC cells. Further studies showed that SLC34A2 interacted with an autophagy-related protein STX17 to promote autophagy and proliferation of ESCC cells by inhibiting the ubiquitination and degradation of STX17. CONCLUSIONS: These findings indicate that SLC34A2 may serve as a prognostic biomarker for ESCC.


Assuntos
Autofagia , Proliferação de Células , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Animais , Feminino , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Cadeia Pesada da Proteína-1 Reguladora de Fusão/metabolismo , Cadeia Pesada da Proteína-1 Reguladora de Fusão/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Prognóstico , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/genética , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Eur J Obstet Gynecol Reprod Biol ; 297: 40-49, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38579545

RESUMO

OBJECTIVE: To systematically review and conduct a meta-analysis to assess the effectiveness of dienogest (DNG) in the prolonged conservative drug management of deep infiltrating endometriosis (DIE). The findings from this study are intended to serve as a valuable reference for clinical decision-making regarding medication in the context of DIE. METHODS: Following the PRISMA Statement, we searched EMBASE, PubMed, The Cochrane Library, Web of Science, and Medline databases for relevant literature published in the public domain from the date of establishment of the database until October 2023. Subsequently, all English publications on clinical studies using DNG for the treatment of DIE were included. Studies involving surgical intervention or drug therapy for postoperative recurrence were excluded. All literature included in the review underwent risk assessment of bias. Two evaluators independently screened the publications, conducted a quality assessment of each article and extracted data. We used Revman 5.4 for the meta-analysis of the included literature. RESULTS: Our final analysis consisted of five clinical studies, involving a total of 256 patients. We found that there were significant improvements in the following indicators post-medication as compared to levels before taking the medication: dysmenorrhea (MD = 4.24, 95 % CI: 2.92-5.56, P < 0.00001), non-menstrual pelvic pain (MD = 3.11, 95 % CI: 2.34-3.88, P < 0.00001), dyspareunia (MD = 1.93, 95 % CI: 1.50-2.37, P < 0.00001), dyschezia (MD = 2.48, 95 % CI: 1.83-3.12, P < 0.00001), and rectosigmoid nodule size (MD = 0.32, 95 % CI: 0.18-0.46, P < 0.00001). Compared with pre-medication levels, the following indicators were significantly worse: headache (RR = 0.03, 95 % CI: 0.00-0.23, P = 0.0006), decreased libido (RR = 0.08, 95 % CI: 0.01-0.62, P = 0.02); and there was no significant improvement in dysuria (P > 0.05). CONCLUSION: DNG showed efficacy in relieving pain-related symptoms and significantly reducing the size of the lesions when used in the drug conservative treatment of DIE.


Assuntos
Endometriose , Nandrolona , Humanos , Feminino , Endometriose/tratamento farmacológico , Nandrolona/análogos & derivados , Nandrolona/uso terapêutico , Resultado do Tratamento , Antagonistas de Hormônios/uso terapêutico
12.
Commun Biol ; 7(1): 512, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684865

RESUMO

Neoantigens derived from somatic mutations in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), the most frequently mutated oncogene, represent promising targets for cancer immunotherapy. Recent research highlights the potential role of human leukocyte antigen (HLA) allele A*11:01 in presenting these altered KRAS variants to the immune system. In this study, we successfully generate and identify murine T-cell receptors (TCRs) that specifically recognize KRAS8-16G12V from three predicted high affinity peptides. By determining the structure of the tumor-specific 4TCR2 bound to KRASG12V-HLA-A*11:01, we conduct structure-based design to create and evaluate TCR variants with markedly enhanced affinity, up to 15.8-fold. This high-affinity TCR mutant, which involved only two amino acid substitutions, display minimal conformational alterations while maintaining a high degree of specificity for the KRASG12V peptide. Our research unveils the molecular mechanisms governing TCR recognition towards KRASG12V neoantigen and yields a range of affinity-enhanced TCR mutants with significant potential for immunotherapy strategies targeting tumors harboring the KRASG12V mutation.


Assuntos
Antígenos de Neoplasias , Proteínas Proto-Oncogênicas p21(ras) , Receptores de Antígenos de Linfócitos T , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/química , Proteínas Proto-Oncogênicas p21(ras)/imunologia , Animais , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/química , Camundongos , Humanos , Neoplasias/imunologia , Neoplasias/genética , Neoplasias/terapia , Mutação , Imunoterapia
13.
J Mol Graph Model ; 129: 108764, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581901

RESUMO

STING (stimulator of interferon genes) is a crucial protein in the innate immune system's response to viral and bacterial infections. In this study, we investigated the mechanistic and energetic mechanism of the conformational transition process of STING activated by cGAMP binding. We found that the STING connector region undergoes an energetically unfavorable rotation during this process, which is compensated by the favorable interaction between cGAMP and the STING ligand binding domain. We further studied several disease-causing mutations and found that the V155 M mutation facilitates a smoother transition in the STING connector region. However, the V147L mutation exhibits unfavorable conformational transition energy, suggesting it may hinder STING activation pathway that relies on connector region rotation. Despite being labeled as hyperactive, the widespread prevalence of V147L/V147I mutations across species implies a neutral character, indicating complexity in its role. Overall, our analysis deepens the understanding of STING activation within the connector region, and targeting this region with compounds may provide an alternative approach to interfering with STING's function.


Assuntos
Proteínas de Membrana , Proteínas de Membrana/química , Conformação Molecular , Mutação
14.
Phys Chem Chem Phys ; 26(13): 10408-10418, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38502252

RESUMO

Nuclear transition protein TNP1 is a crucial player mediating histone-protamine exchange in condensing spermatids. A unique combination of intrinsic disorder and multivalent properties turns TNP1 into an ideal agent for orchestrating the formation of versatile TNP-DNA assemblies. Despite its significance, the physicochemical property and the molecular mechanism followed by TNP1 for histone replacement and DNA condensation are still poorly understood. This study reports the first-time in vitro expression and purification of human TNP1 and investigates the hierarchical dynamics of TNP1-DNA interaction using a combination of computational simulations, biochemical assays, fluorescence imaging, and atomic force microscopy. We explored three crucial facets of TNP1-DNA interactions. Initially, we delve into the molecular binding process that entails fuzzy interactions between TNP1 and DNA at the atomistic scale. Subsequently, we analyze how TNP1 binding affects the electrostatic and mechanical characteristics of DNA and influences its morphology. Finally, we study the biomolecular condensation of TNP1-DNA when subjected to high concentrations. The findings of our study set the foundation for comprehending the potential involvement of TNP1 in histone replacement and DNA condensation in spermatogenesis.


Assuntos
Proteínas Cromossômicas não Histona , Histonas , Masculino , Humanos , Histonas/metabolismo , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Sêmen/metabolismo , Espermatozoides/metabolismo , Proteínas Nucleares
15.
J Child Neurol ; 39(3-4): 113-121, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38488459

RESUMO

OBJECTIVE: The primary objective was to elucidate the epidemiologic characteristics, risk determinants, and clinical outcomes associated with Pseudomonas aeruginosa-induced meningitis. METHODS: All cases of meningitis caused by Pseudomonas aeruginosa that were treated at the hospital between 2012 and 2022 were retrospectively analyzed and detailed. RESULTS: During a 10-year period, only 10 patients satisfied the inclusion criteria. Three patients had previously undergone neurosurgical procedures and 4 patients had leukemia. CONCLUSIONS: Although Pseudomonas aeruginosa meningitis possesses a low incidence rate, the rate of mortality is high. Patients with leukemia or those who have undergone neurosurgery are the most susceptible to diagnosis. Cases of severe neutropenia present only mild or no cerebrospinal fluid pleocytosis. In patients with sensitive Pseudomonas aeruginosa meningitis, the timely use of anti-Pseudomonas carbapenems for intravenous treatment is highly effective. For drug-resistant Pseudomonas aeruginosa meningitis, intrathecal polymyxins administration can be an effective treatment option.


Assuntos
Antibacterianos , Meningites Bacterianas , Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Masculino , Feminino , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Criança , Estudos Retrospectivos , Pré-Escolar , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/complicações , Antibacterianos/uso terapêutico , Lactente , Adolescente
16.
J Pharmacol Exp Ther ; 389(2): 163-173, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38453527

RESUMO

Hepatocellular carcinoma (HCC) is the predominant pathologic type of primary liver cancer. It is a malignant tumor of liver epithelial cells. There are many ways to treat HCC, but the survival rate for HCC patients remains low. Therefore, understanding the underlying mechanisms by which HCC occurs and develops is critical to explore new therapeutic targets. Aldehyde dehydrogenase 2 (ALDH2) is an important player in the redox reaction of ethanol with endogenous aldehyde products released by lipid peroxidation. Increasing evidence suggests that ALDH2 is a crucial regulator of human tumor development, including HCC. Therefore, clarifying the relationship between ALDH2 and HCC is helpful for formulating rational treatment strategies. This review highlights the regulatory roles of ALDH2 in the development of HCC, elucidates the multiple potential mechanisms by which ALDH2 regulates the development of HCC, and summarizes the progress of research on ALDH2 gene polymorphisms and HCC susceptibility. Meanwhile, we envision viable strategies for targeting ALDH2 in the treatment of HCC SIGNIFICANCE STATEMENT: Numerous studies have aimed to explore novel therapeutic targets for HCC, and ALDH2 has been reported to be a critical regulator of HCC progression. This review discusses the functions, molecular mechanisms, and clinical significance of ALDH2 in the development of HCC and examines the prospects of ALDH2-based therapy for HCC.


Assuntos
Aldeído Oxirredutases , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Aldeído Desidrogenase , Aldeído-Desidrogenase Mitocondrial/genética
17.
J Phys Chem Lett ; 15(7): 1956-1961, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38346267

RESUMO

The study of molecular adsorption is crucial for understanding various chemical processes. Spectroscopy offers a convenient and non-invasive way of probing structures of adsorbed states and can be used for real-time observation of molecular binding profiles, including both structural and energetic information. However, deciphering atomic structures from spectral information using the first-principles approach is computationally expensive and time-consuming because of the sophistication of recording spectra, chemical structures, and their relationship. Here, we demonstrate the feasibility of a data-driven machine learning approach for predicting binding energy and structural information directly from vibrational spectra of the adsorbate by using CO adsorption on iron porphyrin as an example. Our trained machine learning model is not only interpretable but also readily transferred to similar metal-nitrogen-carbon systems with comparable accuracy. This work shows the potential of using structure-encoded spectroscopic descriptors in machine learning models for the study of adsorbed states of molecules on transition metal complexes.

18.
Science ; 383(6685): eadj2609, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38305684

RESUMO

Insects rely on a family of seven transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities, such as sweet and bitter. We report structures of Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBDs, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBDs. Sugar binding to LBDs induces local conformational changes, which are subsequently transferred to the PD to cause channel opening. Our studies reveal a structural basis for sugar recognition and activation of GRs.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Açúcares , Percepção Gustatória , Paladar , Animais , Paladar/fisiologia , Percepção Gustatória/fisiologia , Drosophila melanogaster/fisiologia , Proteínas de Drosophila/química , Conformação Proteica
19.
Bioconjug Chem ; 35(2): 203-213, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38343092

RESUMO

The field of clinical surgery frequently encounters challenges related to atypical wound tissue healing, resulting in the development of persistent chronic wounds or aesthetically displeasing scar tissue. The use of wound dressings crafted from mussel adhesive proteins and hyaluronic acid has demonstrated the potential in mitigating these undesirable outcomes. However, the synergistic effects of these two biomaterials remain underexplored. In this study, we have engineered a versatile, degradable, and biocompatible dressing that comprises recombinant 3,4-dihydroxyphenylalanine (DOPA)-modified mussel adhesive proteins and maleimide-functionalized hyaluronic acid. We have successfully fabricated this biocompatible dressing and conducted comprehensive experimental assessments to confirm its hemostatic, antibacterial, and biocompatible characteristics. Importantly, this dressing exclusively incorporates biologically derived materials characterized by low toxicity and minimal immunogenicity, thus holding immense promise for clinical applications in the field of wound healing.


Assuntos
Hemostáticos , Hemostáticos/farmacologia , Hemostáticos/uso terapêutico , Cisteína , Ácido Hialurônico , Antibacterianos/farmacologia , Bandagens , Maleimidas
20.
Angew Chem Int Ed Engl ; 63(14): e202401228, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38354230

RESUMO

Functional thin films, being fabricated by incorporating discrete supramolecular architectures, have potential applications in research areas such as sensing, energy storage, catalysis, and optoelectronics. Here, we have determined that an anion-coordinated triple helicate can be solution-processed into a functional thin film by incorporation into a polymethyl methacrylate (PMMA) matrix. The thin films fabricated by the incorporation of the anion-coordinated triple helicate show multiple optical properties, such as fluorescence, CD, and CPL. In addition, the film has the ability to recognize choline and choline derivatives in a water system. The successful recognition of Ch+ by the film represents the first example of utilizing 'aniono'-supramolecular architectures for biomolecule detection in aqueous solution and opens up a new route for designing biocompatible functional materials.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA