Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.049
Filtrar
1.
J Clin Oncol ; : JCO2302363, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39058972

RESUMO

PURPOSE: The KUNPENG study aimed to evaluate the efficacy and safety of vebreltinib (also known as bozitinib, APL-101, PLB-1001, and CBT-101), a potent and highly selective inhibitor of c-mesenchymal-epithelial transition (MET), in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring c-Met alterations. METHODS: This multicenter, multicohort, open-label, single-arm, phase II trial enrolled patients with c-Met dysregulated, locally advanced or metastatic NSCLC from January 2020 to August 2022 across 17 centers. Cohort 1 included patients with MET exon 14 skipping (METex14)-mutant NSCLC who had not previously received MET inhibitors. Participants were administered vebreltinib at a dosage of 200 mg twice a day in 28-day cycles. The primary end point was the objective response rate (ORR), and the key secondary end point was the duration of response (DoR), both evaluated by a blinded independent review committee according to the RECIST version 1.1. RESULTS: As of August 9, 2022, 52 patients had been enrolled in cohort 1, of whom 35 (67.3%) were treatment-naïve. The ORR reached 75% (95% CI, 61.1 to 86). Among treatment-naïve patients, the ORR was 77.1% (95% CI, 59.9 to 89.6), and in previously treated patients, it was 70.6% (95% CI, 44.0 to 89.7). The disease control rate was 96.2%, with a median DoR of 15.9 months, a median progression-free survival of 14.1 months, and a median overall survival of 20.7 months. The most common treatment-related adverse events were peripheral edema (82.7%), QT prolongation (30.8%), and elevated serum creatinine (28.8%). CONCLUSION: Vebreltinib has shown promising efficacy and a favorable safety profile in patients with METex14-mutant NSCLC.

2.
J Chromatogr A ; 1731: 465163, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39029328

RESUMO

The mevalonate (MVA) pathway plays a crucial role in the occurrence and progression of various diseases, such as osteoporosis, breast cancer, and lung cancer, etc. However, determining all the MVA pathway intermediates is still challenging due to their high polarity, low concentration, chelation effect with metal compartments, and poor mass spectrometric response. In this study, we established a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method coupled with N2, N2, N4, N4-tetramethyl-6-(4-(piperazin-1-ylsulfonyl) phenyl)-1,3,5-triazine-2,4-diamine (Tmt-PP) labeling for the simultaneous analysis of all MVA intermediates in biospecimens. Chemical derivatization significantly improved the chromatographic retention, peak shape, and detection sensitivity of the analytes. Moreover, we employed a method named mass spectrum calculation to achieve the absolute quantification of the isomers, i.e., isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). The established method was fully qualified and applied to explore the difference of these metabolites in cisplatin-resistant non-small cell lung cancer (NSCLC) cells. Additionally, several MVA intermediate analogs, including isopentenyl monophosphate or dimethylallyl monophosphate (IMP/DMAMP), geranyl monophosphate (GMP), 5-triphosphomevalonate (MTP), and isopentenyl triphosphate or dimethylallyl triphosphate (ITP/DMATP), were identified for the first time using a knowledge-driven prediction strategy. We further explored the tissue distribution of these novel metabolites. Overall, this work developed a sensitive quantification method for all MVA intermediates, which will enhance our understanding of the role of this pathway in various health and disease conditions. The novel metabolites we discovered warrant further investigations into their biosynthesis and biological functions.

3.
Neuron ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39032491

RESUMO

Erasing traumatic memory during memory reconsolidation is a promising retrieval-extinction strategy for post-traumatic stress disorder (PTSD). Here, we developed an acute social defeat stress (SDS) mouse model with short-term and re-exposure-evoked long-term social avoidance. SDS-associated traumatic memories were identified to be stored in basolateral amygdala (BLA) engram cells. A single intraperitoneal administration of subanesthetic-dose ketamine within, but not beyond, the re-exposure time window significantly alleviates SDS-induced social avoidance, which reduces the activity and quantity of reactivated BLA engram cells. Furthermore, activation or inhibition of dopaminergic projections from the ventral tegmental area to the BLA effectively mimics or blocks the therapeutic effect of re-exposure with ketamine and is dopamine D2 receptor dependent. Single-cell RNA sequencing reveals that re-exposure with ketamine triggered significant changes in memory-related pathways in the BLA. Together, our research advances the understanding of how ketamine mitigates PTSD symptoms and offers promising avenues for developing more effective treatments for trauma-related disorders.

4.
Chin Med ; 19(1): 94, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956673

RESUMO

BACKGROUND: Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study. OBJECTIVE: This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism. METHODS: The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics. RESULTS: In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 µM, 47 µM, 46.5 µM and 9.8 µM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism. CONCLUSION: The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.

5.
J Asian Nat Prod Res ; : 1-8, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38973288

RESUMO

Two new cucurbitane-type triterpenoid saponins, 2,20ß,22ß-trihydroxy-16α,23(R)-epoxycucurbita-1,5,24-triene-3,11-dione 2-O-ß-D-glucopyranoside (1), 2,20ß,22α-trihydroxy-16α,23(S)-epoxycucurbita-1,5,11,24-tetraene-3-one 2-O-ß-D-glucopyranoside (2) were isolated from the fruit of Citrullus colocynthis (L.) Schrad. Their structures were elucidated by mass spectrometry, IR, 1D, and 2D NMR spectroscopy, etc. Besides, both of the compounds showed significant hepatoprotective activities at 10 µM against paracetamol-induced HepG2 cell damage.

6.
Elife ; 132024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963323

RESUMO

Protein homeostasis (proteostasis) deficiency is an important contributing factor to neurological and metabolic diseases. However, how the proteostasis network orchestrates the folding and assembly of multi-subunit membrane proteins is poorly understood. Previous proteomics studies identified Hsp47 (Gene: SERPINH1), a heat shock protein in the endoplasmic reticulum lumen, as the most enriched interacting chaperone for gamma-aminobutyric acid type A (GABAA) receptors. Here, we show that Hsp47 enhances the functional surface expression of GABAA receptors in rat neurons and human HEK293T cells. Furthermore, molecular mechanism study demonstrates that Hsp47 acts after BiP (Gene: HSPA5) and preferentially binds the folded conformation of GABAA receptors without inducing the unfolded protein response in HEK293T cells. Therefore, Hsp47 promotes the subunit-subunit interaction, the receptor assembly process, and the anterograde trafficking of GABAA receptors. Overexpressing Hsp47 is sufficient to correct the surface expression and function of epilepsy-associated GABAA receptor variants in HEK293T cells. Hsp47 also promotes the surface trafficking of other Cys-loop receptors, including nicotinic acetylcholine receptors and serotonin type 3 receptors in HEK293T cells. Therefore, in addition to its known function as a collagen chaperone, this work establishes that Hsp47 plays a critical and general role in the maturation of multi-subunit Cys-loop neuroreceptors.


Assuntos
Retículo Endoplasmático , Receptores de GABA-A , Humanos , Células HEK293 , Retículo Endoplasmático/metabolismo , Animais , Receptores de GABA-A/metabolismo , Receptores de GABA-A/genética , Ratos , Chaperona BiP do Retículo Endoplasmático/metabolismo , Neurônios/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética
7.
Int J Biol Macromol ; 276(Pt 1): 133652, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971273

RESUMO

Eighteen S rRNA factor 1 (ESF1) is a predominantly nucleolar protein essential for embryogenesis. Our previous studies have suggested that Esf1 is a negative regulator of the tumor suppressor protein p53. However, it remains unclear whether ESF1 contributes to tumorigenesis. In this current research, we find that increased ESF1 expression correlates with poor survival in multiple tumors including pancreatic cancer. ESF1 is able to regulate cell proliferation, migration, DNA damage-induced apoptosis, and tumorigenesis. Mechanistically, ESF1 physically interacts with MDM2 and is essential for maintaining the stability of MDM2 protein by inhibiting its ubiquitination. Additionally, ESF1 also prevented stress-induced stabilization of p53 in multiple cancer cells. Hence, our findings suggest that ESF1 is a potent regulator of the MDM2-p53 pathway and promotes tumor progression.

8.
Life Sci Alliance ; 7(9)2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38986569

RESUMO

Maps of the RNA modification 5-methylcytosine (m5C) often diverge markedly not only because of differences in detection methods, data depand analysis pipelines but also biological factors. We re-analysed bisulfite RNA sequencing datasets from five human cell lines and seven tissues using a coherent m5C site calling pipeline. With the resulting union list of 6,393 m5C sites, we studied site distribution, enzymology, interaction with RNA-binding proteins and molecular function. We confirmed tRNA:m5C methyltransferases NSUN2 and NSUN6 as the main mRNA m5C "writers," but further showed that the rRNA:m5C methyltransferase NSUN5 can also modify mRNA. Each enzyme recognises mRNA features that strongly resemble their canonical substrates. By analysing proximity between mRNA m5C sites and footprints of RNA-binding proteins, we identified new candidates for functional interactions, including the RNA helicases DDX3X, involved in mRNA translation, and UPF1, an mRNA decay factor. We found that lack of NSUN2 in HeLa cells affected both steady-state levels of, and UPF1-binding to, target mRNAs. Our studies emphasise the emerging diversity of m5C writers and readers and their effect on mRNA function.


Assuntos
5-Metilcitosina , Metiltransferases , Biossíntese de Proteínas , RNA Mensageiro , Humanos , 5-Metilcitosina/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Metiltransferases/metabolismo , Metiltransferases/genética , Células HeLa , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Especificidade por Substrato , Metilação , Estabilidade de RNA/genética , tRNA Metiltransferases
9.
Bioorg Chem ; 151: 107618, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39003940

RESUMO

An unprecedented spiro-C-glycoside adduct, heteryunine A (1), along with two uncommon alkaloids featuring a 2,3-diketopiperazine skeleton, heterpyrazines A (2) and B (3), were discovered in the roots of Heterosmilax yunnanensis. The detailed spectroscopic analysis helped to clarify the planar structures of these compounds. Compound 1, containing 7 chiral centers, features a catechin fused with a spiroketal and connects with a tryptophan derivative by a CC bond. Its complex absolute configuration was elucidated by rotating frame overhauser enhancement spectroscopy (ROESY), specific rotation, and the 13C nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculation. The possible biosynthetic routes for 1 were deduced. Compounds 1 and 2 showed significant antifibrotic effects and further research revealed that they inhibited the activation, migration and proliferation of hepatic stellate cells (HSCs) through suppressing the activity of Ras homolog family member A (RhoA).

10.
Alzheimers Dement ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946708

RESUMO

INTRODUCTION: The study aimed to investigate the associations of changes in social isolation, loneliness, or both, with cognitive function. METHODS: Data were from 7299 older adults in the Chinese Longitudinal Healthy Longevity Survey. We defined four change patterns (no, incident, transient, and persistent) for social isolation and loneliness, and created nine-category variable to represent the joint changes. Tobit regression models and Cox models were performed. RESULTS: Incident, transient, and persistent social isolation or loneliness may accelerate cognitive decline (p < 0.05). Incident, transient, and persistent social isolation were associated with higher cognitive impairment risk, while only persistent loneliness was associated with higher cognitive impairment risk (p < 0.001). Notably, short-term or persistent social isolation was associated with accelerated cognitive decline and incident cognitive impairment, regardless of different loneliness change status (p < 0.05). DISCUSSION: Short-term or persistent social isolation and persistent loneliness may be a salient risk factor for cognitive decline and cognitive impairment. HIGHLIGHTS: Incident, transient, and persistent social isolation were associated with accelerated cognitive decline and higher cognitive impairment risk. Persistent loneliness was associated with accelerated cognitive decline and higher cognitive impairment risk. Short-term or persistent social isolation with concurrent different loneliness change status accelerated cognitive decline and higher cognitive impairment risk.

11.
Front Cell Infect Microbiol ; 14: 1433661, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979510

RESUMO

In recent years, the avian influenza virus has emerged as a significant threat to both human and public health. This study focuses on a patient infected with the H10N3 subtype of avian influenza virus, admitted to the Third People's Hospital of Kunming City on March 6, 2024. Metagenomic RNA sequencing and polymerase chain reaction (PCR) analysis were conducted on the patient's sputum, confirming the H10N3 infection. The patient presented severe pneumonia symptoms such as fever, expectoration, chest tightness, shortness of breath, and cough. Phylogenetic analysis of the Haemagglutinin (HA) and neuraminidase (NA) genes of the virus showed that the virus was most closely related to a case of human infection with the H10N3 subtype of avian influenza virus found in Zhejiang Province, China. Analysis of amino acid mutation sites identified four mutations potentially hazardous to human health. Consequently, this underscores the importance of continuous and vigilant monitoring of the dynamics surrounding the H10N3 subtype of avian influenza virus, utilizing advanced genomic surveillance techniques.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza , Vírus da Influenza A , Influenza Humana , Neuraminidase , Filogenia , Humanos , China/epidemiologia , Influenza Humana/virologia , Neuraminidase/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A/genética , Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificação , Mutação , Análise Mutacional de DNA , Animais , Influenza Aviária/virologia , Proteínas Virais/genética , Escarro/virologia , Aves/virologia , Masculino , RNA Viral/genética
12.
Angew Chem Int Ed Engl ; : e202410145, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979674

RESUMO

Tuning the selectivity of CO2 electroreduction reaction (CO2RR) solely by changing electrolyte is a very attractive topic. In this study, we conducted CO2RR in different aqueous electrolytes over bulk metal electrodes. It was discovered that controlled CO2RR could be achieved by modulating cations in the electrochemical double layer. Specifically, ionic liquid cations in the electrolyte significantly inhibits the hydrogen evolution reaction (HER), while yielding high Faraday efficiencies toward CO (FECO) or formate (FEformate) depending on the alkali metal cations. For example, the product could be switched from CO (FECO = 97.3%) to formate (FEformate = 93.5%) by changing the electrolyte from 0.1 M KBr-0.5 M 1-octyl-3-methylimidazolium bromide (OmimBr) to 0.1 M CsBr-0.5M OmimBr aqueous solutions over pristine Cu foil electrode. In situ spectroscopy and theoretical calculations reveal that the ordered structure generated by the assembly of Omim+ under an applied negative potential alters the hydrogen bonding structure of the interfacial water, thereby inhibiting the HER. The difference in selectivity in the presence of different cations is attributed to the hydrogen bonding effect caused by Omim+, which alters the solvated structure of the alkali metal cations and thus affects the stabilization of intermediates of different pathways.

13.
Artigo em Inglês | MEDLINE | ID: mdl-39023787

RESUMO

OBJECTIVE: To do the etiological analysis of ocular herps virus infection, revealing the pathogen species and the distribution of different virus types within the eye. METHODS: Samples were collected from 2017 to 2021 at the Department of Ophthalmology, Peking University Third Hospital and tested using real-time PCR for common ocular viruses: herpes simplex virus 1 (HSV-1), cytomegalovirus (CMV), varicella-zoster virus (VZV) and Epstein-Barr virus (EBV). The pathogenesis of the different viruses was classified and analyzed according to the site of infection. RESULTS: Viral PCR detections were performed on 3627 samples collected over the 5-years and 649 (17.89%) samples contained one or more of the viruses tested. The overall detection rate of CMV was highest at 9.93%. Of all sample types, aqueous humor was the most common (1752 cases), of which 340 were positive (19.41% positive rate). Corneal samples were the next most common, with 1481 cases and 250 positive results (16.88% positive rate). CMV positivity was higher in aqueous humor and corneal samples than other viruses; vitreous body had the highest positive rate at 36.36% (20/55), among which 18 cases were VZV positive. CONCLUSIONS: Distribution of virus types differed among infection sites, with CMV the most common virus type detected in the cornea and aqueous humor, while VZV was the most common virus detected in the vitreous body.

14.
Heliyon ; 10(12): e32963, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38994042

RESUMO

The sustainable advancement of agriculture stands as the fundamental cornerstone of sustainable human progress. This study introduces a data-centric methodological framework founded upon the holistic delineation of measurement, feature assessment, and pathway enhancement for agricultural sustainability. Initially, the research articulates a comprehensive evaluative schema incorporating sub-dimensions encompassing agricultural production, agricultural economics, the agricultural resource environment, and rural society, grounded in sustainable development theory. Subsequently, it devises a methodological apparatus for assessing and enhancing sustainable development capabilities, employing entropy evaluation methods and exploratory spatial data analysis techniques. Employing North Anhui as a case study, the viability of this approach is substantiated. The empirical inquiry conducted within this article operationalizes comprehensive evaluation and explores pathways for optimizing agricultural sustainability, focusing on the period spanning 2011 to 2020 in Northern Anhui. The findings affirm the feasibility and efficacy of the data-driven approach. Recommendations derived from the empirical exploration of agricultural sustainability pathways at the local level offer valuable insights for governmental authorities and policymakers. This research endeavor could be extrapolated to other geographical locales worldwide, fostering innovative strides in the sustainable development of regional agriculture.

15.
Sci Rep ; 14(1): 17069, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39048677

RESUMO

The epithelial-mesenchymal transition (EMT) is a genetic reprogramming that tumor cells utilize for metastasis. Epsin-3 (EPN3) is an endocytic adapter protein involved in clathrin-mediated endocytosis and had been previously linked to EMT in breast cancer and glioma metastasis. In this study, identified the role of epsin-3 in lung adenocarcinoma and metastasis and epsin-3 levels identified using an expression profile analysis of patient data indicated the protein was abnormally overexpressed in lung adenocarcinoma patients and this was directly linked to disease severity. Gene knockdowns of EPN3 in human adenocarcinoma cell line A549 and the non-small cell lung carcinoma cell line H1299 decreased the levels of mesenchymal markers, including vimentin (VIM), N-cadherin (NCAD) and embryonic transcription factors like zinc finger E-box binding homeobox 1(ZEB1), snail, and the key molecules of Wnt pathway such as ß-catenin and resulted in increased expression of the epithelial marker E-cadherin (ECAD). Our data links EPN3 to the EMT process in lung cancer and inhibition of its expression reduced the metastatic and invasive ability of lung adenocarcinoma cells by inhibiting the EMT process.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular , Adenocarcinoma de Pulmão , Movimento Celular , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares , Invasividade Neoplásica , Humanos , Transição Epitelial-Mesenquimal/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/genética , Movimento Celular/genética , Linhagem Celular Tumoral , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Regulação Neoplásica da Expressão Gênica , Feminino , Células A549 , Caderinas/metabolismo , Caderinas/genética , Masculino , Via de Sinalização Wnt , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/genética , Pessoa de Meia-Idade , beta Catenina/metabolismo
16.
Front Immunol ; 15: 1416990, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39055706

RESUMO

Background: Postpartum hemorrhage (PPH) is the primary cause of maternal mortality globally, with uterine atony being the predominant contributing factor. However, accurate prediction of PPH in the general population remains challenging due to a lack of reliable biomarkers. Methods: Using retrospective cohort data, we quantified 48 cytokines in plasma samples from 40 women diagnosed with PPH caused by uterine atony. We also analyzed previously reported hemogram and coagulation parameters related to inflammatory response. The least absolute shrinkage and selection operator (LASSO) and logistic regression were applied to develop predictive models. Established models were further evaluated and temporally validated in a prospective cohort. Results: Fourteen factors showed significant differences between the two groups, among which IL2Rα, IL9, MIP1ß, TNFß, CTACK, prenatal Hb, Lymph%, PLR, and LnSII were selected by LASSO to construct predictive model A. Further, by logistic regression, model B was constructed using prenatal Hb, PLR, IL2Rα, and IL9. The area under the curve (AUC) values of model A in the training set, internal validation set, and temporal validation set were 0.846 (0.757-0.934), 0.846 (0.749-0.930), and 0.875 (0.789-0.961), respectively. And the corresponding AUC values for model B were 0.805 (0.709-0.901), 0.805 (0.701-0.894), and 0.901 (0.824-0.979). Decision curve analysis results showed that both nomograms had a high net benefit for predicting atonic PPH. Conclusion: We identified novel biomarkers and developed predictive models for atonic PPH in women undergoing "low-risk" vaginal delivery, providing immunological insights for further exploration of the mechanism underlying atonic PPH.


Assuntos
Biomarcadores , Citocinas , Hemorragia Pós-Parto , Humanos , Feminino , Gravidez , Biomarcadores/sangue , Hemorragia Pós-Parto/sangue , Hemorragia Pós-Parto/diagnóstico , Hemorragia Pós-Parto/etiologia , Adulto , Citocinas/sangue , Estudos Retrospectivos , Inércia Uterina/sangue , Estudos Prospectivos , Trabalho de Parto/sangue
17.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38953723

RESUMO

The storage ring of the high energy photon source will be driven by five 166.6 MHz ß = 1 quarter-wave superconducting cavities operating at 4 K. A higher-order-mode-damped superconducting cavity was designed with excellent rf and mechanical properties based on the successful development of the proof-of-principle cavity. The mechanical design of the dressed cavity was focused on addressing stress safety throughout the processes, tunability, frequency detuning due to pressure fluctuation, and Lorentz force, among other factors. A new liquid helium vessel was designed along with a comprehensive stiffening scheme to mitigate the surging peak stress on the cavity resulting from the significantly unequal beam pipe size. In the first batch, three cavities were manufactured, and surface preparations were carefully conducted to eliminate defects and etching traces while ensuring cleanliness. The cavity's Q0 at the design voltage of 1.5 MV reached 3.8 × 109 at 4 K, comfortably surpassing the design goal. Field emission onset was not observed during the entire test up to a peak electric field of 60 MV/m, thanks to the optimized processing procedures. Subsequently, one cavity was welded with the newly designed helium vessel and vertically tested at 2 K, achieving an rf performance comparable to the bare cavities, demonstrating the success of the jacketed cavity. This paper presents the design, fabrication, surface preparation, and cryogenic tests of the first higher-order-mode-damped 166.6 MHz ß = 1 superconducting cavity.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38874804

RESUMO

Pulmonary fibrosis (PF) is a persistent interstitial lung condition for which effective treatment options are currently lacking. Zerumbone (zerum), a humulane sesquiterpenoid extracted from Zingiber zerumbet Smith, has been documented in previous studies to possess various pharmacological benefits. The aim of this study was to observe and investigate the therapeutic effects and mechanisms of zerum on pulmonary fibrosis. We utilized a transforming growth factor (TGF)-ß1-induced human lung fibroblast (MRC-5) activation model and a bleomycin-induced pulmonary fibrosis mouse model. Cell counting kit 8 (CCK8) and cell migration assays were performed to assess the effects of zerum on MRC-5 cells. Masson's trichrome, Hematoxylin and Eosin (HE), and Sirius Red staining were conducted for pathological evaluation of lung tissue. Western blot experiments were conducted to measure the protein expression levels of Collagen I, α-SMA, Nrf2, and SIRT1. Immunofluorescence and immunohistochemistry assays were used to detect the expression of reactive oxygen species (ROS), Nrf2, and α-SMA. ELISA was employed to measure the levels of MDA, SOD, and GSH-Px. Our findings from in vitro and in vivo studies demonstrated that zerum significantly inhibited the migration ability of TGF-ß1-induced MRC-5 cells, reduced ROS production in TGF-ß1-induced MRC-5 cells and pulmonary fibrosis mice, and decreased the expression of Collagen I and α-SMA proteins. Additionally, zerum activated the SIRT1/Nrf2 signaling pathway in TGF-ß1-induced MRC-5 cells and pulmonary fibrosis mice. Knockdown of SIRT1 abolished the anti-fibrotic effects of zerum. These results suggest that zerum inhibits TGF-ß1 and BLM-induced cell and mouse pulmonary fibrosis by activating the SIRT1/Nrf2 pathway.

19.
Org Lett ; 26(23): 4857-4862, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38838191

RESUMO

The efficient construction of π-conjugated polycyclic heteroarenes represents a significant task in the field of functional materials. A one-step oxidative tandem cyclization of aromatic acids with (benzo)thiophenes was developed to access planar sulfur-containing polycyclic heteroarenes. This protocol undergoes intermolecular cross-dehydrogenative coupling followed by intramolecular Friedel-Crafts acylation and provides a facile pathway to planar polycyclic compounds from inexpensive reactants. The synthesized heteroarenes serving as lipid-droplet-targeted probes exhibit outstanding performance with favorable biocompatibility and photostability.

20.
Nanomaterials (Basel) ; 14(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38869595

RESUMO

The investigation of the fluorescence mechanism of carbon dots (CDs) has attracted significant attention, particularly the role of the oxygen-containing groups. Dual-CDs exhibiting blue and green emissions are synthesized from glucose via a simple ultrasonic treatment, and the oxidation degree of the CDs is softly modified through a slow natural oxidation approach, which is in stark contrast to that aggressively altering CDs' surface configurations through chemical oxidation methods. It is interesting to find that the intensity of the blue fluorescence gradually increases, eventually becoming the dominant emission after prolonging the oxidation periods, with the quantum yield (QY) of the CDs being enhanced from ~0.61% to ~4.26%. Combining the microstructure characterizations, optical measurements, and ultrafiltration experiments, we hypothesize that the blue emission could be ascribed to the surface states induced by the C-O and C=O groups, while the green luminescence may originate from the deep energy levels associated with the O-C=O groups. The distinct emission states and energy distributions could result in the blue and the green luminescence exhibiting distinct excitation and emission behaviors. Our findings could provide new insights into the fluorescence mechanism of CDs.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...