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1.
Front Oncol ; 14: 1359635, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725625

RESUMO

Background: Epithelial ovarian cancer (EOC) is a significant cause of mortality among gynecological cancers. While Olaparib, a PARP inhibitor, has demonstrated efficacy in EOC maintenance therapy, individual responses vary. This study aims to assess the prognostic significance of body composition and systemic inflammation markers in EOC patients undergoing initial Olaparib treatment. Methods: A retrospective analysis was conducted on 133 EOC patients initiating Olaparib therapy. Progression-free survival (PFS) was assessed through Kaplan-Meier analysis and Cox proportional hazards regression. Pre-treatment computed tomography images were utilized to evaluate body composition parameters including subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), skeletal muscle area index (SMI), and body mineral density (BMD). Inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), serum albumin, and hemoglobin levels, were also measured. Results: The median follow-up duration was 16 months (range: 5-49 months). Survival analysis indicated that high SATI, high VATI, high SMI, high BMD, low NLR, and low PLR were associated with decreased risk of disease progression (all p < 0.05). Multivariate analysis identified several factors independently associated with poor PFS, including second or further lines of therapy (HR = 2.16; 95% CI = 1.09-4.27, p = 0.027), low VATI (HR = 3.79; 95% CI = 1.48-9.70, p = 0.005), low SMI (HR = 2.52; 95% CI = 1.11-5.72, p = 0.027), low BMD (HR = 2.36; 95% CI = 1.22-4.54, p = 0.010), and high NLR (HR = 0.31; 95% CI = 0.14-0.69, p = 0.004). Subgroup analysis in serous adenocarcinoma patients revealed distinct prognostic capabilities of SATI, VATI, SMI, PLR, and NLR. Conclusion: Body composition and inflammation variables hold promise as predictors of therapeutic response to Olaparib in EOC patients. Understanding their prognostic significance could facilitate tailored treatment strategies, potentially improving patient outcomes.

2.
STAR Protoc ; 5(2): 102985, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38691462

RESUMO

Ancient genomics has revolutionized our understanding of human evolution and migration history in recent years. Here, we present a protocol to prepare samples for ancient genomics research. We describe steps for releasing DNA from human remains, DNA library construction, hybridization capture, quantification, and sequencing. We then detail procedures for mapping sequence reads and population genetics analysis. This protocol also outlines challenges in extracting ancient DNA samples and authenticating ancient DNA to uncover the genetic history and diversity of ancient populations. For complete details on the use and execution of this protocol, please refer to Tao et al.1.

3.
Materials (Basel) ; 17(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38473545

RESUMO

In comparison to conventional EDM, micro EDM distinguishes itself through its brief discharge duration, narrow discharge channel radius, and concentrated energy density. However, there remains a paucity of comprehensive research on the surface formation characteristics in this domain. This paper delves into the formation mechanism of the recast layer in micro EDM workpieces, scrutinizing the primary factors that influence the formation process and the morphological attributes of the recast layer. We conducted a series of single-pulse experiments and micro EDM trials. Utilizing surface fitting tools, our experimental findings facilitated the derivation of a relational expression between the recast layer thickness of high-speed steel and the discharge parameters in micro EDM. Notably, when the energy is below 100 µJ, the recast layer thickness remains under 10 µm. Specifically, at an energy level of 16 µJ, opting for a smaller capacitance of 2200 pf and a higher voltage of 120 V in micro EDM results in a thinner recast layer. This study serves as a cornerstone for future efforts aimed at controlling and assessing the surface morphology of micro EDM.

4.
Eur J Radiol ; 175: 111433, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38554673

RESUMO

PURPOSE: Multiple lipid metabolism pathways alterations are associated with clear cell renal cell carcinoma (ccRCC) development and aggressiveness. In this study, we aim to develop a novel radiogenomics signature based on lipid metabolism-related genes (LMRGs) that may accurately predict ccRCC patients' survival. MATERIALS AND METHODS: First, 327 ccRCC were used to screen survival-related LMRGs and construct a gene signature based on The Cancer Genome Atlas (TCGA) database. Then, 182 ccRCC were analyzed to establish radiogenomics signature linking LMRGs signature to radiomic features in The Cancer Imaging Archive (TCIA) database included enhanced CT images and transcriptome sequencing data. Lastly, we validated the prognostic power of the identified radiogenomics signature using these patients of TCIA and the Third Xiangya Hospital. RESULTS: We identified the LMRGs signature, consisting of 13 genes, which could efficiently discriminate between low-risk and high-risk patients and serve as an independent and reliable predictor of overall survival (OS). Radiogenomics signature, comprised of 9 radiomic features, was created and could accurately predict the expression level of LMRGs signature (low- or high-risk) for patients. The predictive performance of this radiogenomics signature was demonstrated through AUC values of 0.75 and 0.74 for the training and validation sets (at a ratio of 7:3), respectively. Radiogenomics signature was proven to be an independent risk factor for OS by multivariable analysis (HR = 4.98, 95 % CI:1.72-14.43, P = 0.003). CONCLUSIONS: The LMRGs radiogenomics signature could serve as a novel prognostic predictor.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Metabolismo dos Lipídeos , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/genética , Neoplasias Renais/diagnóstico por imagem , Masculino , Prognóstico , Feminino , Metabolismo dos Lipídeos/genética , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Idoso , Biomarcadores Tumorais/genética , Taxa de Sobrevida , Valor Preditivo dos Testes
5.
Folia Neuropathol ; 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38174678

RESUMO

Ischemic stroke (IS) is a well-known acute cerebrovascular disease characterized by high disability, morbidity, and recurrence rates with no effective treatments. Dexmedetomidine (DEX), a selective a2-adrenoceptor agonist used in anaesthesiology and pain management, has been found to exhibit neuroprotective effects in various diseases. However, its role in IS and the underlying mechanisms remains to be determined. Hence, the aim of the present study was to investigate the neuroprotective role of DEX in the recovery of mice following middle cerebral artery occlusion (MCAO). Mice were used to establish the animal model, and then DEX was injected. Behavioural tests (neurological function assessments, grip test, and rotarod test), brain water content measurement, ELISA, and measurement of oxidative stress were performed. DEX activated a2-adrenoceptor and resulted in reduced brain injury, as indicated by the decreased brain water content, S100 Calcium Binding Protein B (S100B) content, and neuron-specific enolase (NSE) content, whilst also inhibiting oxidative stress, as indicated by the increased total antioxidant capacity, catalase, glutathione, and superoxide dismutase levels, and decreased malondialdehyde and glutathione oxidized levels. Neuroinflammation was also reduced as indicated by the decrease in IFN-g, IL-1a, IL-1b, IL-6, TNF-a, and MMP levels, improved the recovery of neurological function, as indicated by the decreased neurological function score and mNSS, and increased grip strength and rotarod performance in MCAO mice. These combined results suggest that DEX may be a novel strategy for the treatment of IS.

6.
Molecules ; 28(20)2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37894590

RESUMO

A D-A type of luminophore, TPA-CDP, was designed and synthesized by using triphenylamine (TPA) as D (electron donor), 1,3-diaryl pyrazole with cyano groups (CDP) as A (electron acceptor) and employing a cyanovinyl segment as a recognition group. Firstly, TPA-CDP demonstrates effective fluorescence quenching as a sensor for I- by the nucleophilic addition reaction of the cyanovinyl segment with a high level of sensitivity, selectivity and a low determination limit of 4.43 µM. Interestingly, TPA-CDP exhibited an AIE phenomenon with the fw value reaching 50%. In addition, TPA-CDP displayed distinct mechanochromic fluorescence behavior with 70 nm red shift, which was observed over four repeated cycles. Furthermore, the mechanochromic fluorescence behavior of TPA-CDP, as observed in powder XRD experiments, was found to be associated with the morphological transition from a crystalline state to an amorphous state. These results confirm the significant potential of CDP as a powerful electron-deficient component in the creation of D-A-type mechanochromic fluorescence materials and biosensors for detecting I-.

7.
Curr Biol ; 33(22): 4995-5002.e7, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37852263

RESUMO

The study of southwest China is vital for understanding the dispersal and development of farming because of the coexistence of millet and rice in this region since the Neolithic period.1,2 However, the process of the Neolithic transition in southwest China is largely unknown, mainly due to the lack of ancient DNA from the Neolithic period. Here, we report genome-wide data from 11 human samples from the Gaoshan and Haimenkou sites with mixed farming of millet and rice dating to between 4,500 and 3,000 years before present in southwest China. The two ancient groups derived approximately 90% of their ancestry from the Neolithic Yellow River farmers, suggesting a demic diffusion of millet farming to southwest China. We inferred their remaining ancestry to be derived from a Hòabìnhian-related hunter-gatherer lineage. We did not detect rice farmer-related ancestry in the two ancient groups, which indicates that they likely adopted rice farming without genetic assimilation. We, however, observed rice farmer-related ancestry in the formation of some present-day Tibeto-Burman populations. Our results suggested the occurrence of both demic and cultural diffusion in the development of Neolithic mixed farming in some parts of southwest China.


Assuntos
Milhetes , Rios , Humanos , Milhetes/genética , Agricultura , Genoma , Fazendas , DNA Antigo , Migração Humana
8.
Dalton Trans ; 52(37): 13358-13366, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37671899

RESUMO

Six phosphorescence-emitting metal-organic mononuclear Cu(I) complexes, namely four quinoline-containing three-coordinate Cu(I) complexes and two N-heterocyclic carbene-containing four-coordinate Cu(I) complexes, have been successfully developed and fully characterized. All these Cu(I) complexes include the same bis(2-diphenylphosphinophenyl)ether bidentate auxiliary ligand. Significantly, four-coordinate Cu(I) complexes 1 and 2 display typical aggregation-induced emission phenomena. Their solid samples of luminogenic complexes 1-6 emit a variety of different phosphorescence. Furthermore, solid-state phosphorescence of these Cu(I) complexes can be effectively manipulated by external mechanical force. Remarkably, luminophores 1, 2 and 5 exhibit blue-shifted mechanoluminochromism responses, while luminophores 3, 4 and 6 present red-shifted mechanoluminochromism characteristics. All of the observed mechano-responsive phosphorescence changes of solids 1-6 are reversible by the method of solvent fuming. Powder X-ray diffraction results confirm that the reversible mechanically induced phosphorescence changes of complexes 1-6 are due to the mutual transformation of ordered crystalline and metastable amorphous states.

9.
Materials (Basel) ; 16(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37297233

RESUMO

Thin-rim gears are widely used in industrial fields such as aerospace and electric vehicles due to the advantage of light weight. Yet, the root crack fracture failure of thin-rim gears significantly limits their application and further affects the reliability and safety of high-end equipment. In this work, the root crack propagation behavior of thin-rim gears is experimentally and numerically investigated. The crack initiation position and crack propagation path for different backup ratio gears are simulated using gear finite element (FE) models. The crack initiation position is determined using the maximum gear root stress position. An extended FE method coupled with commercial software ABAQUS is used to simulate the gear root crack propagation. The simulation results are then verified by conducting experimental tests for different backup ratio gears based on a dedicated designed single-tooth bending test device.

10.
Spectrochim Acta A Mol Biomol Spectrosc ; 298: 122723, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37119634

RESUMO

With the deepening of the concept of recycling economy and green chemistry, selective detection and capture of Cu2+ from lake water by biosorbent are of great significance. Herein, the Cu2+ ion-imprinted polymers (RH-CIIP) with organosilane containing hydroxyl and Schiff base groups (OHSBG) as ion-receptor, fluorescent chromophores and cross-linking agent, and Cu2+ as template ion, were fabricated via surface ion imprinting technology by employing mesoporous silica MCM-41 (RH@MCM-41) as supporter. The RH-CIIP could be exploited as a fluorescent sensor for Cu2+ with high selective compared with Cu2+ non-imprinted polymers (RH-CNIP). Additionally, the LOD was calculated to be 5.62 µg/L, which is far below WHO standard for Cu2+ in drinking water of 2 mg/L, and more lower than the reported methods. Moreover, the RH-CIIP can also be utilized as an adsorbent for the effective elimination of Cu2+ from lake water with the adsorption capacity of 87.8 mg/g. Besides, the kinetic features of adsorption were well defined by the pseudo-second-order model and the sorption isotherm was in agreement with the Langmuir model. Meanwhile, the interaction of RH-CIIP and Cu2+ was investigated using theoretical calculations and XPS. Finally, RH-CIIP was able to remove almost 99 % Cu2+ in lake water samples that satisfied the drink water standard.

11.
Cell Res ; 33(2): 147-164, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36670290

RESUMO

Acute liver failure (ALF) is a life-threatening disease that occurs secondary to drug toxicity, infection or a devastating immune response. Orthotopic liver transplantation is an effective treatment but limited by the shortage of donor organs, the requirement for life-long immune suppression and surgical challenges. Stem cell transplantation is a promising alternative therapy for fulminant liver failure owing to the immunomodulatory abilities of stem cells. Here, we report that when transplanted into the liver, human endoderm stem cells (hEnSCs) that are germ layer-specific and nontumorigenic cells derived from pluripotent stem cells are able to effectively ameliorate hepatic injury in multiple rodent and swine drug-induced ALF models. We demonstrate that hEnSCs tune the local immune microenvironment by skewing macrophages/Kupffer cells towards an anti-inflammatory state and by reducing the infiltrating monocytes/macrophages and inflammatory T helper cells. Single-cell transcriptomic analyses of infiltrating and resident monocytes/macrophages isolated from animal livers revealed dramatic changes, including changes in gene expression that correlated with the change of activation states, and dynamic population heterogeneity among these cells after hEnSC transplantation. We further demonstrate that hEnSCs modulate the activation state of macrophages/Kupffer cells via cystatin SN (CST1)-mediated inhibition of interferon signaling and therefore highlight CST1 as a candidate therapeutic agent for diseases that involve over-activation of interferons. We propose that hEnSC transplantation represents a novel and powerful cell therapeutic treatment for ALF.


Assuntos
Falência Hepática Aguda , Células-Tronco Pluripotentes , Animais , Humanos , Endoderma , Inflamação , Fígado , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/terapia , Cistatinas Salivares , Suínos , Interferons/metabolismo
12.
Int J Biol Macromol ; 217: 229-242, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-35788004

RESUMO

This study presents the preparation of cellulose micro-nanofibrils (CMNFs) from Enteromorpha (EP) and the application in PVA/acetylated distarch phosphate (ADSP)/CMNFs composite films. The Micro-nano scale, hydrophilicity, and strong hydrogen bond characteristics of CMNFs prepared form EP by acid hydrolysis were confirmed through the granular statistics, XRD analysis and chemical structure analysis. With the addition of CMNFs, the ultimate tensile strength and elongation at break of composite films are increased by 42.4 % and 90.3 %. An original Weibull statistical analysis shows the impact of CMNFs' added amount on strength distribution and ultimate stress. SEM and polarizing microscope images show the CMNFs' dispersion state in that films is optimal, when their addition was to be 2 %-3 % of total dry weight of PVA/ADSP matrix, which is consistent with the results of Weibull modulus analysis. The main thermal weight-loss process of the composite film is divided into four stages, CMNFs can significantly increase the thermostability at 280 °C to 400 °C. The experiment of water contact angle and water vapor transmission rate of the composite films confirmed that CMNFs can improve films' hydrophilicity. This study provides basis for the preparation of hydrophilic CMNFs and mechanism of modification study PVA-based composites.


Assuntos
Celulose , Álcool de Polivinil , Celulose/química , Interações Hidrofóbicas e Hidrofílicas , Fosfatos , Álcool de Polivinil/química , Vapor , Resistência à Tração
13.
RSC Adv ; 12(20): 12355-12362, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35480345

RESUMO

In this study, a new fluorescent sensor dicyanoisophorone Rhodanine-3-acetic acid (DCI-RDA) (DCI-RDA) has been developed by employing a DCI-based push-pull dye as the fluorophore and RDA as the recognition moiety for the simultaneous sensing of Fe3+ and Hg2+ with a large Stokes Shift (162 nm), high selectivity and sensitivity, and low LOD (1.468 µM for Fe3+ and 0.305 µM for Hg2+). In particular, DCI-RDA has a short response time (30 s). The Job's plot method in combination with 1H NMR titration and theoretical calculations was used to determine the stoichiometry of both DCI-RDA-Fe3+/Hg2+ complexes to be 1 : 1. Moreover, DCI-RDA is applied as a fluorescent probe for imaging in HeLa cells and zebrafish, indicating that it can be potentially applied for Fe3+/Hg2+ sensing in the field of biology.

14.
Front Chem ; 10: 842712, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281566

RESUMO

Photoacoustic (PA) imaging has received more and more attention on disease diagnosis and fundamental scientific research. It is still challenging to amplify their imaging ability and reduce the toxicity of inorganic materials and exogenous contrast agents. Semiconducting polymer nanoparticles (SPNs), as a new type of contrast agent, have the advantages of low toxicity, flexible structure adjustment, good photostability, and excellent photothermal conversion efficiency. SPNs containing benzo(1,2-c;4,5-c')bis(1,2,5)thiadiazole (BBT) units, as the most classic second near-infrared window (NIR-II, 1,000-1700 nm) PA contrast agents, can achieve light absorption in the NIR-II region, thereby effectively reducing light loss in biological tissues and improving imaging resolution. This mini review summarizes the recent advances in the design strategy of BBT and its derivative-based semiconducting polymer nanoparticles for second near-infrared photoacoustic imaging. The evolution process of BBT blocks provides a unique perspective for the design of high-performance NIR-II PA contrast agents.

15.
J Colloid Interface Sci ; 616: 605-617, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35231704

RESUMO

Polyaniline (PANI)/Epoxy copolymer as a core material was synthesized via a chemical oxidation method. Various analytical techniques, including scanning electron microscope, Fourier transform infrared spectroscopy, energy dispersive spectroscopy, thermogravimetry, and electrochemical impedance spectroscopy, were used to characterize the morphology, compositions, and self-healing and anticorrosion properties of the prepared microcapsules and coatings. The prepared PANI/Epoxy copolymer showed the best electrochemical corrosion resistance when the ratio of PANI to epoxy was 0.05: 1 (wt.:wt.). For the mass fraction of the core (PANI/Epoxy copolymer) of 60.84 ± 0.06 wt%, the mean particle diameter of the prepared microcapsules was 4.20 ± 0.92 µm. The coatings with 15 wt% microcapsules possessed excellent self-healing performance and corrosion resistance. The low-frequency impedance modulus at 0.01 Hz of scratched coatings immersed in the NaCl solution for 24 h was 5.27 × 106 Ω·cm2. Scratched self-repairing coating samples were able to resist corrosion for 384 h; thus, the microcapsules can be used to significantly extend the service life of the coatings. Microcapsule-containing PANI/Epoxy copolymers are expected to find use in anticorrosion coating systems, where the coatings could be applied directly on rusty steel surfaces.

16.
J Hazard Mater ; 424(Pt A): 127203, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34600392

RESUMO

With the deepening of the concept of recycling economy and green chemistry, selective capture of Cu(II) from wastewater by biosorbent and reuse of the spent Cu(II)-loaded adsorbent are of great significance. Herein, we synthesized composite of rice husk (RH) with mesoporous silica MCM-41 (RH@MCM-41) modified by organosilane containing amino and schiff groups as functional monomer and cross-linking agent. The silica modified RH@MCM-41 was employed as supporter to fabricate copper ion-imprinted polymers as absorbents (named as RM-CIIPs) via surface ion imprinting technique. Adsorption isotherms, kinetics, selectivity and mechanism of RM-CIIPs to remove Cu(II) were investigated with respect to different adsorption condition. Furthermore, we explored the catalytic activity of spent Cu(II)-loaded adsorbent in Glaser coupling reaction. Batch adsorption studies revealed that RM-CIIP-3 prepared with functional monomer shows the best adsorption capacity (91.4 mg/g) for Cu(II), and adsorption equilibrium could be reached within 30 min. RM-CIIP-3 exhibited an excellent selectivity for capturing Cu(II) and reusability in six adsorption/desorption cycles. More importantly, the spent Cu(II)-loaded adsorbent could be used as bio-heterogeneous catalyst and afford the desired product (1,4-diphenylbutadiyne) in 99.1% yield. Our research indicates an eco-friendly systematic strategy to utilize the waste material as an adsorbent for removing heavy metals and catalyst for industry.


Assuntos
Oryza , Poluentes Químicos da Água , Adsorção , Cobre , Concentração de Íons de Hidrogênio , Cinética , Polímeros , Poluentes Químicos da Água/análise
17.
Front Cell Neurosci ; 15: 671473, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33994950

RESUMO

The role of the dopaminergic pathway in general anesthesia and its potential mechanisms are still unknown. In this study, we usedc-Fos staining combined with calcium fiber photometry recording to explore the activity of ventral tegmental area (VTA) dopaminergic neurons(VTA-DA) and nucleus accumbens (NAc) neurons during sevoflurane anesthesia. A genetically encoded dopamine (DA) sensor was used to investigate thefunction of the NAc in sevoflurane anesthesia. Chemogenetics and optogenetics were used to explore the role of the VTA-DA in sevofluraneanesthesia. Electroencephalogram (EEG) spectra, time of loss of righting reflex (LORR) and recovery of righting reflex (RORR) were recorded asassessment indicators. We found that VTA-DA and NAc neurons were inhibited during the induction period and were activated during the recoveryperiod of sevoflurane anesthesia. The fluorescence signals of dopamine decreased in the induction of and increased in the emergence from sevoflurane anesthesia.Activation of VTA-DA and the VTADA-NAc pathway delayed the induction and facilitated the emergence accompanying with thereduction of delta band and the augmentation of the gamma band. These data demonstrate that VTA-DA neurons play a critical role in modulating sevofluraneanesthesia via the VTADA-NAc pathway.

18.
Front Mol Neurosci ; 14: 628996, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746711

RESUMO

Since their introduction in the 1840s, one of the largest mysteries of modern anesthesia are how general anesthetics create the state of reversible loss of consciousness. Increasing researchers have shown that neural pathways that regulate endogenous sleep-wake systems are also involved in general anesthesia. Recently, the Lateral Habenula (LHb) was considered as a hot spot for both natural sleep-wake and propofol-induced sedation; however, the role of the LHb and related pathways in the isoflurane-induced unconsciousness has yet to be identified. Here, using real-time calcium fiber photometry recordings in vivo, we found that isoflurane reversibly increased the activity of LHb glutamatergic neurons. Then, we selectively ablated LHb glutamatergic neurons in Vglut2-cre mice, which caused a longer induction time and less recovery time along with a decrease in delta-band power in mice under isoflurane anesthesia. Furthermore, using a chemogenetic approach to specifically activate LHb glutamatergic neurons shortened the induction time and prolonged the recovery time in mice under isoflurane anesthesia with an increase in delta-band power. In contrast, chemogenetic inhibition of LHb glutamatergic neurons was very similar to the effects of selective lesions of LHb glutamatergic neurons. Finally, optogenetic activation of LHb glutamatergic neurons or the synaptic terminals of LHb glutamatergic neurons in the rostromedial tegmental nucleus (RMTg) produced a hypnosis-promoting effect in isoflurane anesthesia with an increase in slow wave activity. Our results suggest that LHb glutamatergic neurons and pathway are vital in modulating isoflurane anesthesia.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33193801

RESUMO

OBJECTIVE: Hua-Feng-Dan (HFD) is a Chinese medicine for stroke. This study is to predict and verify potential molecular targets and pathways of HFD against stroke using network pharmacology. METHODS: The TCMSP database and TCMID were used to search for the active ingredients of HFD, and GeneCards and DrugBank databases were used to search for stroke-related target genes to construct the "component-target-disease" by Cytoscape 3.7.1, which was further filtered by MCODE to build a core network. The STRING database was used to obtain interrelationships by topology and to construct a protein-protein interaction network. GO and KEGG were carried out through DAVID Bioinformatics. Autodock 4.2 was used for molecular docking. BaseSpace was used to correlate target genes with the GEO database. RESULTS: Based on OB ≥ 30% and DL ≥ 0.18, 42 active ingredients were extracted from HFD, and 107 associated targets were obtained. PPI network and Cytoscape analysis identified 22 key targets. GO analysis suggested 51 cellular biological processes, and KEGG suggested that 60 pathways were related to the antistroke mechanism of HFD, with p53, PI3K-Akt, and apoptosis signaling pathways being most important for HFD effects. Molecular docking verified interactions between the core target (CASP8, CASP9, MDM2, CYCS, RELA, and CCND1) and the active ingredients (beta-sitosterol, luteolin, baicalein, and wogonin). The identified gene targets were highly correlated with the GEO biosets, and the stroke-protection effects of Xuesaitong in the database were verified by identified targets. CONCLUSION: HFD could regulate the symptoms of stroke through signaling pathways with core targets. This work provided a bioinformatic method to clarify the antistroke mechanism of HFD, and the identified core targets could be valuable to evaluate the antistroke effects of traditional Chinese medicines.

20.
Org Biomol Chem ; 18(32): 6357-6363, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32760945

RESUMO

The development of a novel near-infrared (NIR) probe for the detection of toxic Hg2+ in organisms with high selectivity and sensitivity is of great interest but remains a great challenge. Hence, in this work, a new NIR fluorescence enhanced sensor (TBBA), which contains a D-A structure as the NIR fluorophore and rhodanine-3-acetic acid as the receptor, has been developed for the detection of Hg2+ with high selectivity, sensitivity, low limit of detection (13.10 nM) and good binding constant (2.37 × 104 M-1). The mechanism of TBBA response to Hg2+ was further proved by 1H NMR titration, HRMS, and theoretical calculations. Furthermore, TBBA is applied as a fluorescent probe for imaging living cells and zebrafish, indicating that it can be potentially applied for Hg2+ sensing in both environmental and biology fields.


Assuntos
Corantes Fluorescentes/química , Mercúrio/análise , Imagem Óptica , Tiadiazóis/química , Animais , Linhagem Celular , Corantes Fluorescentes/síntese química , Humanos , Raios Infravermelhos , Estrutura Molecular , Tiadiazóis/síntese química , Peixe-Zebra
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