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1.
Genome Biol Evol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748818

RESUMO

Bitter taste perception plays a critical role in deterring animals from consuming harmful and toxic substances. To characterize the evolution of primate Tas2r, test the generality of Tas2r duplication in Cercopithecidae species, and examine whether dietary preferences have shaped the Tas2r repertoire of primate species, we identified Tas2r in the genomes of 35 primate species, including 16 Cercopithecidae, 6 Hominidae, 4 Cebidae, 3 Lemuridae, and 6 other species. The results showed that the total number of primate Tas2r ranged from 27 to 51, concentrating on 2-4 scaffolds of each species. Closely related genes were tandemly duplicated in the same scaffold. Phylogenetic construction revealed that Tas2r genes can be divided into 21 clades, including anthropoid-, Strepsirrhini-, and Cercopithecidea-specific Tas2r duplications. Phylogenetically independent contrast analysis revealed that the number of intact Tas2r significantly correlated with feeding preferences. Altogether, our data supports diet as a driver of primate Tas2r evolution, and Cercopithecidae species have developed some specific Tas2r duplication during evolution. These results are probably because most Cercopithecidae species feed on plants containing many toxins, and it is necessary to develop specialized Tas2r to protect them from poisoning.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38607204

RESUMO

Objective: To investigate the impact of graded management based on delirium prediction modeling on the improvement of recovery of cardiac surgery patients. Methods: Three hundred and twenty patients admitted to the Department of Critical Care Medicine of Nanjing Hospital affiliated with Nanjing Medical University from June 2021 to December 2023 after Type A aortic coarctation were selected as study subjects. They were grouped according to the randomized scale method and divided into 160 cases in each the control group and the observation group. In the control group, conventional nursing measures were adopted, and in the observation group, graded nursing interventions were carried out according to the established delirium risk prediction model. Comparison between the two groups in terms of the intensive care unit (ICU) monitoring time, hospitalization time, duration of delirium, and delirium incidence, and investigated nursing satisfaction, and quality of care scores. Results: Compared with the control group, the observation group's ICU custody time, hospitalization time, and delirium duration, decreased, and the quality of care, and satisfaction increased (P < .05). At the same time, the incidence of delirium in the observation group was also lower than that in the control group (P < .05). Conclusion: The graded management based on the delirium prediction model can effectively reduce the incidence of postoperative delirium in critically ill patients with Type A aortic coarctation, and at the same time improve patient satisfaction and quality of care.

3.
BMC Oral Health ; 24(1): 461, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627719

RESUMO

BACKGROUND: It is uncertain if mean platelet volume and periodontitis are related. The objective of this study was to examine the association between levels of mean platelet volume and moderate/severe periodontitis in adult persons who inhabit the U.S. METHODS: We screened 6,809 people from the National Health and Nutrition Examination Survey (NHANES 2009-2012). Mean platelet volume was measured in the Mobile Examination Centers (MECs) using the Beckman Coulter analyzer. The category of periodontitis was defined by the CDC/AAP using clinical periodontal parameters. Multiple logistic regression models were employed to examine the distribution for covariate differences across the various independent groups. Four models were employed to examine the relationship between mean platelet volume level and periodontitis. Smoothed curve fitting was utilized to confirm the linearity of the relationships. To determine the impact of factors on the connection between MPV and periodontitis, subgroup analysis and interaction testing were utilized. RESULTS: Results from the multiple logistic regression analysis indicate a significant association between moderate/severe periodontitis and the mean platelet level, even after considering any potential confounding variables (OR = 1.090, 95% CI: 1.019-1.166, P-value = 0.01211). Additionally, those in the upper tertile of mean platelet volume levels had a 21.6% higher probability of developing periodontitis when compared with those in the least tertile of mean platelet levels (OR = 1.216, 95% CI:1.052-1.406, P-value = 0.00816). Moreover, it showed a positive correlation between mean platelet volume (MPV) and moderate/severe periodontitis. Subgroup analyses indicated a positive association between the level of mean platelet volume and moderate/severe periodontitis among individuals who were under 60 years of age, had low income, were obese, never smoked, were heavy drinkers, had hypertension, and had no cardiovascular disease (p < 0.05). However, none of the subgroups exhibited significant interactions (p for interaction > 0.05). CONCLUSION: A correlation has been found between mean platelet volume levels and periodontal disease in individuals residing in the United States.


Assuntos
Volume Plaquetário Médio , Periodontite , Adulto , Humanos , Estados Unidos , Estudos Transversais , Inquéritos Nutricionais , Plaquetas
4.
Chem Sci ; 15(16): 5869-5896, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38665521

RESUMO

With the continuous development of laser technology and the increasing demand for lasers of different frequencies in the infrared (IR) spectrum, research on infrared nonlinear optical (NLO) crystals has garnered growing attention. Currently, the three main commercially available types of borate materials each have their drawbacks, which limit their applications in various areas. Rare-earth (RE)-based chalcogenide compounds, characterized by the unique f-electron configuration, strong positive charges, and high coordination numbers of RE cations, often exhibit distinctive optical responses. In the field of IR-NLO crystals, they have a research history spanning several decades, with increasing interest. However, there is currently no comprehensive review summarizing and analyzing these promising compounds. In this review, we categorize 85 representative examples out of more than 400 non-centrosymmetric (NCS) compounds into four classes based on the connection of different asymmetric building motifs: (1) RE-based chalcogenides containing tetrahedral motifs; (2) RE-based chalcogenides containing lone-pair-electron motifs; (3) RE-based chalcogenides containing [BS3] and [P2Q6] motifs; and (4) RE-based chalcohalides and oxychalcogenides. We provide detailed discussions on their synthesis methods, structures, optical properties, and structure-performance relationships. Finally, we present several favorable suggestions to further explore RE-based chalcogenide compounds. These suggestions aim to approach these compounds from a new perspective in the field of structural chemistry and potentially uncover hidden treasures within the extensive accumulation of previous research.

5.
Cell Death Differ ; 31(5): 683-696, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38589496

RESUMO

Protein phosphatase 1 catalytic subunit gamma (PPP1CC) promotes DNA repair and tumor development and progression, however, its underlying mechanisms remain unclear. This study investigated the molecular mechanism of PPP1CC's involvement in DNA repair and the potential clinical implications. High expression of PPP1CC was significantly correlated with radioresistance and poor prognosis in human nasopharyngeal carcinoma (NPC) patients. The mechanistic study revealed that PPP1CC bound to Ku70/Ku80 heterodimers and activated DNA-PKcs by promoting DNA-PK holoenzyme formation, which enhanced nonhomologous end junction (NHEJ) -mediated DNA repair and led to radioresistance. Importantly, BRCA1-BRCA2-containing complex subunit 3 (BRCC3) interacted with PPP1CC to enhance its stability by removing the K48-linked polyubiquitin chain at Lys234 to prevent PPP1CC degradation. Therefore, BRCC3 helped the overexpressed PPP1CC to maintain its high protein level, thereby sustaining the elevation of DNA repair capacity and radioresistance. Our study identified the molecular mechanism by which PPP1CC promotes NHEJ-mediated DNA repair and radioresistance, suggesting that the BRCC3-PPP1CC-Ku70 axis is a potential therapeutic target to improve the efficacy of radiotherapy.


Assuntos
Reparo do DNA por Junção de Extremidades , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Proteína Fosfatase 1 , Tolerância a Radiação , Humanos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Proteína Fosfatase 1/metabolismo , Proteína Fosfatase 1/genética , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/metabolismo , Tolerância a Radiação/genética , Prognóstico , Linhagem Celular Tumoral , Autoantígeno Ku/metabolismo , Autoantígeno Ku/genética , Animais , Proteína Quinase Ativada por DNA/metabolismo , Proteína Quinase Ativada por DNA/genética , Camundongos Nus , Feminino , Masculino , Reparo do DNA , Camundongos
6.
Artigo em Inglês | MEDLINE | ID: mdl-38483764

RESUMO

Chronic obstructive pulmonary disease (COPD) is a chronic lung inflammatory disease that causes restricted airflow and breathing difficulties. In this work, we attempted to explore the salutary effects of rutaecarpine on COPD-induced rats. Healthy Wistar rats were employed in this study and exposed to cigarette smoke to initiate COPD. The rutaecarpine was given to the rats at 20 and 30 mg/kg dosages, respectively, for 12 weeks. Body weight gain, food uptake, and food efficiency were assessed after treatment completion. The grip strength test was performed to assess muscle strength. The C-reactive protein (CRP), leptin, inflammatory cytokines, and oxidative stress markers were assessed using the corresponding assay kits. The inflammatory cells on the bronchoalveolar lavage fluid (BALF) were counted using Wright-Giemsa staining. The respiratory functions of the experimental rats were measured. The histopathological analysis was done on the lung tissues. The rutaecarpine treatment effectively increased body weight gain, food uptake, and food efficiency in the COPD rats. The levels of leptin were increased, and CRP was reduced by the rutaecarpine. The rutaecarpine regulated the respiratory functions and reduced the inflammatory cell counts and pro-inflammatory markers in the COPD rats. The levels of antioxidants were increased by the rutaecarpine treatment in the COPD rats. The findings of the lung histopathological study also demonstrated the therapeutic effects of rutaecarpine. Overall, the findings of the current study witness the salutary role of rutaecarpine against cigarette smoke-induced COPD in rats. Therefore, it was clear that rutaecarpine could be a promising salutary candidate to treat COPD.

7.
Funct Integr Genomics ; 24(1): 24, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38315263

RESUMO

This study is aimed at investigating the roles of Toll-like receptor 4 (TLR4) and microRNA-7 (miR-7) in colorectal cancer (CRC) development and progression. We assessed TLR4 and miR-7 expression in CRC cells and tissues using reverse transcription-quantitative polymerase chain reaction. The relationship between miR-7 and TLR4 was analyzed through dual luciferase reporter assays. MTT, wound healing, and cell invasion assays were conducted to examine the effects of TLR4 and miR-7 on CRC cell proliferation, migration, and invasion. Western blotting was used to explore the involvement of the TRAF6/NF-κB signaling pathway. miR-7 was underexpressed in CRC, while TLR4 levels were increased. miR-7 negatively regulated TLR4 expression and its knockdown enhanced CRC cell proliferation, migration, and invasion. TLR4 knockdown had the opposite effects. The TRAF6/NF-κB pathway was linked to TLR4's role in tumor progression. miR-7 might inhibit TRAF6/NF-κB target a signaling pathway of TLR4 and promote CRC occurrence. miR-7 may therefore be used as a sensitive biomarker in CRC patients.


Assuntos
Neoplasias Colorretais , MicroRNAs , Receptor 4 Toll-Like , Humanos , Proliferação de Células , Neoplasias Colorretais/genética , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/genética , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
8.
Aging (Albany NY) ; 16(4): 3257-3279, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38334966

RESUMO

Lipolysis, the key process releasing fat acids to generate energy in adipose tissues, correlates with starvation resistance. Nevertheless, its detail mechanisms remain elusive. BubR1, an essential mitotic regulator, ensures proper chromosome alignment and segregation during mitosis, but its physiological functions are largely unknown. Here, we use Drosophila adult fat body, the major lipid storage organ, to study the functions of BubR1 in lipolysis. We show that both whole body- and fat body-specific BubR1 depletions increase lipid degradation and shorten the lifespan under fasting but not feeding. Relish, the conserved regulator of IMD signaling pathway, acts as the downstream target of BubR1 to control the expression level of Bmm and modulate the lipolysis upon fasting. Thus, our study reveals new functions of BubR1 in starvation-induced lipolysis and provides new insights into the molecular mechanisms of lipolysis mediated by IMD signaling pathway.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Drosophila/genética , Lipólise , Proteínas de Drosophila/metabolismo , Transdução de Sinais , Lipídeos , Proteínas de Ciclo Celular/metabolismo
9.
J Environ Manage ; 355: 120251, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38422844

RESUMO

Drought synchronously affects the water cycle and interferes with the carbon cycle in terrestrial ecosystems. Ecosystem water use efficiency (WUE), serving as a vital metric for assessing the interplay between water and carbon cycles, has found extensively use in exploring how ecosystems responses to drought. However, the effects of soil moisture drought on WUE are still poorly recognized. Taking Ziya River Basin as an example, the spatial-temporal variations of WUE from 2001 to 2020 were estimated by the Penman-Monteith-Leuning Version 2 (PML-V2) data. Based on the Standardized Soil Moisture Index (SSI) calculated from Soil Moisture of China by in situ data, version 1.0 (SMCI1.0) data, the sensitivity and thresholds of different vegetation WUE to drought magnitudes were investigated, and the influences of both lagged and cumulative effects of drought on WUE were further analyzed. Results showed that the annual mean WUE was 2.160 ± 0.975 g C kg-1 H2O-1 in the Ziya River Basin, with a significant increasing trend of 0.037 g C kg-1 H2O-1 yr-1 (p < 0.05). For all the vegetation types, the WUE reached the maximum value at a certain drought threshold (SSI = -1.5 ± 0.1). The dominant factor controlling WUE sensitivity to drought changed from evapotranspiration (ET) to gross primary production (GPP) when severe drought transformed into extreme drought. Significant lagged and cumulative effects were found in the response of WUE to drought in nearly 58.64 % (72.94 %) of the study area, with an average time scale of 6.65 and 2.11 months (p < 0.05) respectively. Drought resistance in descending order was: forest > shrub > grassland > cropland. Our findings enrich the understanding of the coupled carbon and water cycle processes in terrestrial ecosystems and their response to soil moisture drought in the context of global climate change.


Assuntos
Ecossistema , Solo , Secas , Água , China
10.
Adv Sci (Weinh) ; 11(16): e2306174, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38368261

RESUMO

Patients with concurrent intrahepatic cholangiocarcinoma (ICC) and hepatolithiasis generally have poor prognoses. Hepatolithiasis is once considered the primary cause of ICC, although recent insights indicate that bacteria in the occurrence of hepatolithiasis can promote the progression of ICC. By constructing in vitro and in vivo ICC models and patient-derived organoids (PDOs), it is shown that Escherichia coli induces the production of a novel RNA, circGLIS3 (cGLIS3), which promotes tumor growth. cGLIS3 binds to hnRNPA1 and G3BP1, resulting in the assembly of stress granules (SGs) and suppression of hnRNPA1 and G3BP1 ubiquitination. Consequently, the IKKα mRNA is blocked in SGs, decreasing the production of IKKα and activating the NF-κB pathway, which finally results in chemoresistance and produces metastatic phenotypes of ICC. This study shows that a combination of Icaritin (ICA) and gemcitabine plus cisplatin (GP) chemotherapy can be a promising treatment strategy for ICC.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Progressão da Doença , Escherichia coli , NF-kappa B , Grânulos de Estresse , Animais , Humanos , Camundongos , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/metabolismo , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Modelos Animais de Doenças , DNA Helicases , Escherichia coli/genética , Escherichia coli/metabolismo , Gencitabina , NF-kappa B/metabolismo , NF-kappa B/genética , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/genética , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/genética , Transdução de Sinais/genética , Grânulos de Estresse/metabolismo , Grânulos de Estresse/genética
11.
RSC Adv ; 14(10): 6508-6520, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38390513

RESUMO

Produced gas re-injection is an effective and eco-friendly approach for enhancing oil recovery from shale oil reservoirs. However, the interactions between different gas phase components, and the oil phase and rocks are still unclear during the re-injection process. This study aims to investigate the potential of produced gas re-injection, particularly focusing on the effects of methane (CH4) content in the produced gas on shale oil displacement. Molecular dynamics simulations were employed to analyze the interactions between gas, oil, and matrix phases with different CH4 proportions (0%, 25%, 50%, and 100%), alkanes and under various burial depth. Results show that a 25% CH4 content in the produced gas achieves almost the same displacement effect as pure carbon dioxide (CO2) injection. However, when the CH4 content increases to 50% and 100%, the interaction between gas and quartz becomes insufficient to effectively isolate oil from quartz, causing only expansion and slight dispersion. Interestingly, the presence of CH4 has a synergistic effect on CO2, facilitating the diffusion of CO2 into the oil film. During the gas stripping process, CO2 is the main factor separating oil from quartz, while CH4 mainly contributes to oil expansion. In addition, for crude oil containing a large amount of light alkanes, extracting light components through mixed gas may be more effective than pure CO2. This study offers valuable insights for applications of produced gas re-injection to promote shale oil recovery.

12.
J Org Chem ; 89(4): 2351-2363, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38301039

RESUMO

An effective and stereoselective synthesis of halogenated (E)-4-methylenechromanes with a sulfonyl group was developed via the copper-catalyzed sulfonylative annulation/halogenation of 1,7-enynes, in which sodium sulfinates were used as the sulfonyl reagents and tetrabutylammonium halide provided the halogen sources. The formed alkenyl C-X bonds were valuable and can efficiently undergo the subsequent hydrolysis, alkenylation, alkynylation, arylation, alkylthiolation, and alkoxylation to furnish a series of highly functionalized 4-methylenechromanes.

13.
J Exp Clin Cancer Res ; 43(1): 14, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38191501

RESUMO

BACKGROUND: Metastasis has emerged as the major reason of treatment failure and mortality in patients with nasopharyngeal carcinoma (NPC). Growing evidence links abnormal DNA methylation to the initiation and progression of NPC. However, the precise regulatory mechanism behind these processes remains poorly understood. METHODS: Bisulfite pyrosequencing, RT-qPCR, western blot, and immunohistochemistry were used to test the methylation and expression level of NEURL3 and its clinical significance. The biological function of NEURL3 was examined both in vitro and in vivo. Mass spectrometry, co-immunohistochemistry, immunofluorescence staining, and ubiquitin assays were performed to explore the regulatory mechanism of NEURL3. RESULTS: The promoter region of NEURL3, encoding an E3 ubiquitin ligase, was obviously hypermethylated, leading to its downregulated expression in NPC. Clinically, NPC patients with a low NEURL3 expression indicated an unfavorable prognosis and were prone to develop distant metastasis. Overexpression of NEURL3 could suppress the epithelial mesenchymal transition and metastasis of NPC cells in vitro and in vivo. Mechanistically, NEURL3 promoted Vimentin degradation by increasing its K48-linked polyubiquitination at lysine 97. Specifically, the restoration of Vimentin expression could fully reverse the tumor suppressive effect of NEURL3 overexpression in NPC cells. CONCLUSIONS: Collectively, our study uncovers a novel mechanism by which NEURL3 inhibits NPC metastasis, thereby providing a promising therapeutic target for NPC treatment.


Assuntos
Neoplasias Nasofaríngeas , Ubiquitina-Proteína Ligases , Humanos , Carcinoma Nasofaríngeo/genética , Ubiquitina-Proteína Ligases/genética , Vimentina/genética , Transição Epitelial-Mesenquimal , Neoplasias Nasofaríngeas/genética
14.
Nanotechnology ; 35(17)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38252998

RESUMO

Silicon solar cell is the most mature photovoltaic conversion device, and in order to further improve the performance of the device, application of downshifting films has become a research hotspot. In this paper, CsPbBr3perovskite quantum dot/EVA composite adhesive film was prepared by melting method with CsPbBr3perovskite quantum dot film under solution processing as masterbatch and EVA particles as excipient. The effect of synthesis conditions on the luminescence properties of the composite films were thoroughly studied. The optimized CsPbBr3perovskite quantum dot/EVA composite adhesive film has excellent performance, and its light transmission reaches 85%. The CsPbBr3perovskite quantum dot/EVA composite adhesive film absolutely improves the efficiency of silicon solar cells by 1.08%, which is much higher than that of pure EVA adhesive film (0.63%). In addition, the device efficiencies have almost no change after 30 d in the air, maintaining the working stability of the device and contributing to industrial applications. This study provides a novel, industrial and low-cost synthesis route for the synthesis of CsPbBr3perovskite quantum dot/EVA composite adhesive film, which is expected to have broad application.

15.
Nurs Crit Care ; 29(1): 22-31, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37161792

RESUMO

BACKGROUND: Patient compliance is crucial to maintaining the awake prone position, which has been found to be intolerable by several patients. Addressing patients' compliance while being treated with awake prone positioning and prolonging its duration may be prerequisites for further research. AIM: This study was conducted to explore the personal experiences of non-intubated patients during the implementation of awake prone positioning. STUDY DESIGN: We conducted a qualitative study recruiting a purposive sample of twelve adult patients diagnosed with COVID-19 who were previously treated with awake prone positioning. They were recruited from an intermediate care unit (that provides pre- and post-intensive care) in a COVID-19-designated hospital in Nanjing, China from July 15, 2021, to September 20, 2021. Data were collected through individual in-depth interviews and then analysed using Colaizzi's phenomenological method. RESULTS: Content analysis of the interviews revealed two main themes, each containing three and four sub-themes, respectively, as follows: (1) barriers to the implementation of awake prone positioning, including (i) generalised discomfort, (ii) a lack of both understanding and trust, and (iii) low satisfaction with the implementation plan; (2) factors promoting the implementation of awake prone positioning, including (i) health education and supervision, (ii) self-motivation and support from healthcare staff and family members, (iii) finding a comfortable position and having access to entertainment, and (iv) symptom improvement. CONCLUSIONS: Healthcare staff should clarify the mechanism underlying the effectiveness of the awake prone position to patients to eliminate any doubts that they may have. Psychological support and appropriate supervision should be emphasised. Pain relief programmes should also be established, including the use of a comfortable prone posture in conjunction with access to entertainment. Finally, individualised awake prone positioning protocols should be formulated according to patients' living habits and attempted in combination with out-of-bed activities. These measures may help to enhance the experience and compliance of patients undergoing the treatment. RELEVANCE TO CLINICAL PRACTICE: For future instances involving the implementation of awake prone positioning, several measures should be established and implemented alongside it, including a health education programme, supervision programme, support system, and pain relief programme. Personalisation should also be considered during its implementation. These measures may help to enhance the compliance of patients and prolong the duration of the awake prone position.


Assuntos
COVID-19 , Adulto , Humanos , COVID-19/terapia , Decúbito Ventral , Vigília , Cuidados Críticos , Dor
16.
Analyst ; 149(2): 418-425, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38078792

RESUMO

Carboxylesterase (CES), a main hydrolysis enzyme family in the human body, plays a crucial role in drug metabolism. Among them, CES1 and CES2 are the primary subtypes, and each exhibits distinct distribution and functions. However, convenient and non-invasive methods for distinguishing them and the real-time monitoring of CES2 are relatively rare, hindering the further understanding of physiological functions and underlying mechanisms. In this study, we have designed, synthesized, and evaluated the first selective bioluminescent probe (CBP 1) for CES2 with high sensitivity, high specificity and rapid reactivity. This probe offers a promising approach for the real-time detection of CES2 and its dynamic fluctuations both in vitro and in vivo.


Assuntos
Hidrolases de Éster Carboxílico , Humanos , Hidrolases de Éster Carboxílico/metabolismo
17.
Int Immunopharmacol ; 126: 111285, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38061118

RESUMO

OBJECTIVES: HWH486 inhibits Bruton's tyrosine kinase and therefore shows promise as a treatment against rheumatoid arthritis and chronic spontaneous urticaria. This phase I trial assessed tolerability, safety, pharmacokinetics and pharmacodynamics of a single oral dose of HWH486 capsules in healthy adults. METHODS: A single-center, randomized, double-blind, placebo-controlled, dose-escalation study from 10 to 800 mg was conducted in 96 healthy Chinese adults, of whom 80 received HWH486 and 16 received placebo. RESULTS: A total of 96 subjects were enrolled, and all completed the study. In the HWH486 group, mean Tmax ranged from 1.03 to 2.00 h, and mean T1/2 ranged from 0.85 to 8.67 h across the dose range from 10 to 800 mg. Mean Cmax increased linearly with dose, while mean AUC0-t increased non-linearly. Occupancy of Bruton's tyrosine kinase peaked within 0.50-4.00 h after administration across the dose groups, and the delay until peak occupancy decreased with increasing dose. Twenty-five subjects (31.25 %) in the HWH486 group experienced 35 treatment-emergent adverse events, while four subjects (25.00 %) in the placebo group experienced eight such events. CONCLUSIONS: HWH486 is well tolerated and safe in healthy adults, in whom it can strongly bind Bruton's tyrosine kinase. These findings justify clinical studies of HWH486 efficacy against autoimmune diseases.


Assuntos
Artrite Reumatoide , Doenças Autoimunes , Adulto , Humanos , Tirosina Quinase da Agamaglobulinemia , Área Sob a Curva , Método Duplo-Cego , Artrite Reumatoide/tratamento farmacológico , Relação Dose-Resposta a Droga , Voluntários Saudáveis
18.
Front Endocrinol (Lausanne) ; 14: 1282675, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075076

RESUMO

Introduction: Contrast-induced nephropathy (CIN) is a common complication of percutaneous coronary intervention (PCI). Identifying patients at high CIN risk remains challenging. The triglyceride-glucose (TyG) index may help predict CIN but evidence is limited. We conducted a meta-analysis to evaluate the diagnostic value of TyG index for CIN after PCI. Methods: A systematic literature search was performed in MEDLINE, Cochrane, and EMBASE until August 2023 (PROSPERO registration: CRD42023452257). Observational studies examining TyG index for predicting CIN risk in PCI patients were included. This diagnostic meta-analysis aimed to evaluate the accuracy of the TyG index in predicting the likelihood of CIN. Secondary outcomes aimed to assess the pooled incidence of CIN and the association between an elevated TyG index and the risk of CIN. Results: Five studies (Turkey, n=2; China, n=3) with 3518 patients (age range: 57.6 to 68.22 years) were included. The pooled incidence of CIN was 15.3% [95% confidence interval (CI) 11-20.8%]. A high TyG index associated with increased CIN risk (odds ratio: 2.25, 95% CI 1.82-2.77). Pooled sensitivity and specificity were 0.77 (95% CI 0.59-0.88) and 0.55 (95% CI 0.43-0.68) respectively. Analysis of the summary receiver operating characteristic (sROC) curve revealed an area under the curve of 0.69 (95% CI 0.65-0.73). There was a low risk of publication bias (p = 0.81). Conclusion: The TyG index displayed a noteworthy correlation with the risk of CIN subsequent to PCI. However, its overall diagnostic accuracy was found to be moderate in nature. While promising, the TyG index should not be used in isolation for CIN screening given the heterogeneity between studies. In addition, the findings cannot be considered conclusive given the scarcity of data. Further large-scale studies are warranted to validate TyG cutoffs and determine how to optimally incorporate it into current risk prediction models. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023452257, identifier CRD42023452257.


Assuntos
Nefropatias , Intervenção Coronária Percutânea , Humanos , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Intervenção Coronária Percutânea/efeitos adversos , Medição de Risco , Glucose/efeitos adversos , Triglicerídeos , Nefropatias/induzido quimicamente , Nefropatias/diagnóstico , Nefropatias/epidemiologia
19.
Front Immunol ; 14: 1320683, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38149257

RESUMO

Background: Postoperative infectious complications (PICs) are major concerns. Early and accurate diagnosis is critical for timely treatment and improved outcomes. Presepsin is an emerging biomarker for bacterial infections. However, its diagnostic efficacy for PICs across surgical specialties remains unclear. Methods: In this study, a systematic search on MEDLINE, Embase, Google Scholar, and Cochrane Library was performed on September 30, 2023, to identify studies that evaluated presepsin for diagnosing PICs. PIC is defined as the development of surgical site infection or remote infection. Pooled sensitivity, specificity, and hierarchical summary receiver operating characteristic (HSROC) curves were calculated. The primary outcome was the assessment of the efficacy of presepsin for PIC diagnosis, and the secondary outcome was the investigation of the reliability of procalcitonin or C-reactive protein (CRP) in the diagnosis of PICs. Results: This meta-analysis included eight studies (n = 984) and revealed that the pooled sensitivity and specificity of presepsin for PIC diagnosis were 76% (95% confidence interval [CI] 68%-82%) and 83% (95% CI 75%-89%), respectively. The HSROC curve yielded an area under the curve (AUC) of 0.77 (95% CI 0.73-0.81). Analysis of six studies on procalcitonin showed a combined sensitivity of 78% and specificity of 77%, with an AUC of 0.83 derived from the HSROC. Meanwhile, data from five studies on CRP indicated pooled sensitivity of 84% and specificity of 79%, with the HSROC curve yielding an AUC of 0.89. Conclusion: Presepsin exhibits moderate diagnostic accuracy for PIC across surgical disciplines. Based on the HSROC-derived AUC, CRP has the highest diagnostic efficacy for PICs, followed by procalcitonin and presepsin. Nonetheless, presepsin demonstrated greater specificity than the other biomarkers. Further study is warranted to validate the utility of and optimize the cutoff values for presepsin. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023468358.


Assuntos
Receptores de Lipopolissacarídeos , Pró-Calcitonina , Reprodutibilidade dos Testes , Biomarcadores , Proteína C-Reativa/análise
20.
Animals (Basel) ; 13(21)2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37958179

RESUMO

Food grinding is supposed to be influenced by multiple factors. However, how those factors affecting this behavior remain unclear. In this study, we investigated the effect of food restriction on food grinding in Brandt's voles (Lasiopodomys brandtii), as well as the potential role of the gut microbiota in this process, through a comparison of the variations between voles with different food supplies. Food restriction reduced the relative amount of ground food to a greater extent than it lowered the relative food consumption, and altered the abundance of Staphylococcus, Aerococcus, Jeotgalicoccus, and Un--s-Clostridiaceae bacterium GM1. Fecal acetate content for the 7.5 g-food supply group was lower than that for the 15 g-food supply group. Our study indicated that food restriction could effectively inhibit food grinding. Further, Un--s-Clostridiaceae bacterium GM1 abundance, Aerococcus abundance, and acetate content were strongly related to food grinding. Variations in gut microbial abundance and short-chain fatty acid content induced by food restriction likely promote the inhibition of food grinding. These results could potentially provide guidance for reducing food waste during laboratory rodent maintenance.

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