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1.
J Environ Manage ; 359: 121034, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38703649

RESUMO

Frequent algal blooms cause algal cells and their algal organic matter (AOM) to become critical precursors of disinfection by-products (DBPs) during water treatment. The presence of bromide ion (Br-) in water has been demonstrated to affect the formation laws and species distribution of DBPs. However, few researchers have addressed the formation and toxicity alteration of halonitromethanes (HNMs) from algae during disinfection in the presence of Br-. Therefore, in this work, Chlorella vulgaris was selected as a representative algal precursor to investigate the formation and toxicity alteration of HNMs during UV/chloramination involving Br-. The results showed that the formation concentration of HNMs increased and then decreased during UV/chloramination. The intracellular organic matter of Chlorella vulgaris was more susceptible to form HNMs than the extracellular organic matter. When the Br-: Cl2 mass ratio was raised from 0.004 to 0.08, the peak of HNMs total concentration increased 33.99%, and the cytotoxicity index and genotoxicity index of HNMs increased 67.94% and 22.80%. Besides, the formation concentration and toxicity of HNMs increased with increasing Chlorella vulgaris concentration but decreased with increasing solution pH. Possible formation pathways of HNMs from Chlorella vulgaris during UV/chloramination involving Br- were proposed based on the alteration of nitrogen species and fluorescence spectrum analysis. Furthermore, the formation laws of HNMs from Chlorella vulgaris in real water samples were similar to those in deionized water samples. This study contributes to a better comprehension of HNMs formation from Chlorella vulgaris and provides valuable information for water managers to reduce hazards associated with the formation of HNMs.

2.
Nat Commun ; 15(1): 2951, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580660

RESUMO

Hepatitis B virus is a globally distributed pathogen and the history of HBV infection in humans predates 10000 years. However, long-term evolutionary history of HBV in Eastern Eurasia remains elusive. We present 34 ancient HBV genomes dating between approximately 5000 to 400 years ago sourced from 17 sites across Eastern Eurasia. Ten sequences have full coverage, and only two sequences have less than 50% coverage. Our results suggest a potential origin of genotypes B and D in Eastern Asia. We observed a higher level of HBV diversity within Eastern Eurasia compared to Western Eurasia between 5000 and 3000 years ago, characterized by the presence of five different genotypes (A, B, C, D, WENBA), underscoring the significance of human migrations and interactions in the spread of HBV. Our results suggest the possibility of a transition from non-recombinant subgenotypes (B1, B5) to recombinant subgenotypes (B2 - B4). This suggests a shift in epidemiological dynamics within Eastern Eurasia over time. Here, our study elucidates the regional origins of prevalent genotypes and shifts in viral subgenotypes over centuries.


Assuntos
Vírus da Hepatite B , Migração Humana , Humanos , Vírus da Hepatite B/genética , Filogenia , Genótipo , Evolução Biológica , DNA Viral/genética
3.
Molecules ; 29(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38675718

RESUMO

Utilizing solar energy for photocatalytic CO2 reduction is an attractive research field because of its convenience, safety, and practicality. The selection of an appropriate photocatalyst is the key to achieve efficient CO2 reduction. Herein, we report the synthesis of TiO2/CuPc heterojunctions by compositing CuPc with TiO2 microspheres via a hydroxyl-induced self-assembly process. The experimental investigations demonstrated that the optimal TiO2/0.5CuPc photocatalyst exhibited a significantly enhanced CO2 photoreduction rate up to 32.4 µmol·g-1·h-1 under 300 W xenon lamp irradiation, which was 3.7 times that of the TiO2 microspheres alone. The results of photoelectrochemical experiments indicated that the construction of the heterojunctions by introducing CuPc effectively promoted the separation and transport of photogenerated carriers, thus enhancing the catalytic effect of the photocatalyst.

4.
Small ; : e2312288, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38431966

RESUMO

The development of capable of simultaneously modulating the sluggish electrochemical kinetics, shuttle effect, and lithium dendrite growth is a promising strategy for the commercialization of lithium-sulfur batteries. Consequently, an elaborate preparation method is employed to create a host material consisting of multi-channel carbon microspheres (MCM) containing highly dispersed heterostructure Fe3 O4 -FeTe nanoparticles. The Fe3 O4 -FeTe@MCM exhibits a spontaneous built-in electric field (BIEF) and possesses both lithophilic and sulfophilic sites, rendering it an appropriate host material for both positive and negative electrodes. Experimental and theoretical results reveal that the existence of spontaneous BIEF leads to interfacial charge redistribution, resulting in moderate polysulfide adsorption which facilitates the transfer of polysulfides and diffusion of electrons at heterogeneous interfaces. Furthermore, the reduced conversion energy barriers enhanced the catalytic activity of Fe3 O4 -FeTe@MCM for expediting the bidirectional sulfur conversion. Moreover, regulated Li deposition behavior is realized because of its high conductivity and remarkable lithiophilicity. Consequently, the battery exhibited long-term stability for 500 cycles with 0.06% capacity decay per cycle at 5 C, and a large areal capacity of 7.3 mAh cm-2 (sulfur loading: 9.73 mg cm-2 ) at 0.1 C. This study provides a novel strategy for the rational fabrication of heterostructure hosts for practical Li-S batteries.

5.
Micromachines (Basel) ; 15(1)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38258241

RESUMO

The purpose of this study is to explore the possibility of using graphene-zinc oxide-hydroxyapatite (GO/ZnO/nHAp) composite microspheres as bone regeneration materials by making use of the complementary advantages of nanocomposites, so as to provide reference for the clinical application of preventing and solving bacterial infection after implantation of synthetic materials. Firstly, GO/ZnO composites and hydroxyapatite nanoparticles were synthesized using the hydrothermal method, and then GO/ZnO/nHAp composite microspheres were prepared via high-temperature sintering. The graphene-zinc oxide-calcium phosphate composite microspheres were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), energy dispersion spectroscopy (EDS), water contact angle measurement, degradation and pH determination, and differential thermal analysis (DiamondTG/DTA). The biocompatibility, osteogenic activity, and antibacterial activity of GO/ZnO/nHAp composite microspheres were further studied. The results of the cell experiment and antibacterial experiment showed that 0.5% and 1% GO-ZnO-nHAp composite microspheres not only had good biocompatibility and osteogenic ability but also inhibited Escherichia coli and Staphylococcus aureus by more than 45% and 70%. Therefore, GO/ZnO/nHAp composite microspheres have good physical and chemical properties and show good osteogenic induction and antibacterial activity, and this material has the possibility of being used as a bone regeneration material.

6.
Adv Mater ; 36(14): e2309748, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38165653

RESUMO

One-for-all phototheranostics, referring to a single component simultaneously exhibiting multiple optical imaging and therapeutic modalities, has attracted significant attention due to its excellent performance in cancer treatment. Benefitting from the superiority in balancing the diverse competing energy dissipation pathways, aggregation-induced emission luminogens (AIEgens) are proven to be ideal templates for constructing one-for-all multimodal phototheranostic agents. However, to this knowledge, the all-round AIEgens that can be triggered by a second near-infrared (NIR-II, 1000-1700 nm) light have not been reported. Given the deep tissue penetration and high maximum permissible exposure of the NIR-II excitation light, herein, this work reports for the first time an NIR-II laser excitable AIE small molecule (named BETT-2) with multimodal phototheranostic features by taking full use of the advantage of AIEgens in single molecule-facilitated versatility as well as synchronously maximizing the molecular donor-acceptor strength and conformational distortion. As formulated into nanoparticles (NPs), the high performance of BETT-2 NPs in NIR-II light-driven fluorescence-photoacoustic-photothermal trimodal imaging-guided photodynamic-photothermal synergistic therapy of orthotopic mouse breast tumors is fully demonstrated by the systematic in vitro and in vivo evaluations. This work offers valuable insights for developing NIR-II laser activatable one-for-all phototheranostic systems.


Assuntos
Nanopartículas , Neoplasias , Animais , Camundongos , Luz , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Linhagem Celular Tumoral
7.
J Hazard Mater ; 465: 133253, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38103299

RESUMO

In this study, we have successfully developed a novel dual-response fluorescent probe, NACou, designed for the visual and quantitative detection of HClO/H2S in real water samples and liquid beverages by a thin-film sensing platform. Additionally, NACou demonstrated efficacy for sensing HClO/H2S in HeLa cells, plants and zebrafish through distinct fluorescent channels, yielding satisfactory results. NACou exhibited a multi-modal fluorescence response mechanism for detecting HClO and H2S with remarkable low detection limits of 27.8 nM and 34.4 nM, accompanied by outstanding fluorescent enhancement (209-fold and 148-fold, respectively). These advantages position NACou as a potent molecular tool for HClO and H2S sensing. The specific recognition performance of NACou towards HClO/H2S were confirmed through fluorescence spectroscopy, mass analysis and UV-vis spectroscopy. Importantly, the thin-film sensing platform with the visible fluorescence change can enable rapid assays for water quality and food safety monitoring, showcasing significant practical application value. Impressively, NACou has been employed in warning against liver injury induced by multiple drugs, allowing for the exploration of the pathogenesis and degree of drug-induced injury.


Assuntos
Sulfeto de Hidrogênio , Peixe-Zebra , Humanos , Animais , Células HeLa , Ácido Hipocloroso , Corantes Fluorescentes/química , Espectrometria de Fluorescência , Sulfeto de Hidrogênio/análise
8.
Opt Express ; 31(24): 39703-39716, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38041286

RESUMO

Resolution of single molecule localization microscopy (SMLM) depends on the localization accuracy, which can be improved by utilizing engineered point spread functions (PSF) with delicate shapes. However, the intrinsic pixelation effect of the detector sensor will deteriorate PSFs under different sampling rates. The influence of the pixelation effect to the achieved 3D localization accuracy for different PSF shapes under different signal to background ratio (SBR) and pixel dependent readout noise has not been investigated in detail so far. In this work, we proposed a framework to characterize the 3D localization accuracy of pixelated PSF at different sampling rates. Four different PSFs (astigmatic PSF, double helix (DH) PSF, Tetrapod PSF and 4Pi PSF) were evaluated and the pixel size with optimal 3D localization performance were derived. This work provides a theoretical guide for the optimal design of sampling rate for 3D super resolution imaging.

9.
Front Pharmacol ; 14: 1154780, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37860115

RESUMO

Background: A new, effective anti-tuberculosis (TB) regimen containing bedaquiline (BDQ) and pyrifazimine (TBI-166) has been recommended for a phase IIb clinical trial. Preclinical drug-drug interaction (DDI) studies of the combination of BDQ and TBI-166 have been designed to support future clinical trials. In this study, we investigated whether a DDI between BDQ and TBI-166 affects the pharmacokinetics of BDQ. Methods: We performed in vitro quantification of the fractional contributions of the fraction of drug metabolism by individual CYP enzymes (f m) of BDQ and the inhibition potency of key metabolic pathways of TBI-166. Furthermore, we conducted an in vivo steady-state pharmacokinetics study in a murine TB model and healthy BALB/c mice. Results: The in vitro f m value indicated that the CYP3A4 pathway contributed more than 75% to BDQ metabolism to N-desmethyl-bedaquiline (M2), and TBI-166 was a moderate (IC50 2.65 µM) potential CYP3A4 inhibitor. Coadministration of BDQ and TBI-166 greatly reduced exposure to metabolite M2 (AUC0-t 76310 vs 115704 h ng/mL, 66% of BDQ alone), whereas the exposure to BDQ and TBI-166 did not changed. The same trend was observed both in healthy and TB model mice. The plasma concentration of M2 decreased significantly after coadministration of BDQ and TBI-166 and decreased further during treatment in the TB model. Conclusions: In conclusion, our results showed that the combination of BDQ and TBI-166 significantly reduced exposure to the toxic metabolite M2 by inhibiting the activity of the CYP3A4 pathway. The potential safety and efficacy benefits demonstrated by the TB treatment highly suggest that coadministration of BDQ and TBI-166 should be studied further.

10.
Anal Bioanal Chem ; 415(29-30): 7187-7196, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37801118

RESUMO

Isoniazid (INH) and pyrazinamide (PZA) are both the first-line anti-tuberculosis drugs in clinical treatment. It is notable that there are serious side effects of the drugs along with upregulation of reactive nitrogen species, mainly including peripheral neuritis, gastrointestinal reactions, and acute drug-induced liver injury (DILI). Among them, DILI is the most common clinical symptom as well as the basic reason of treatment interruption, protocol change, and drug resistance. As vital reactive nitrogen species (RNS), peroxynitrite (ONOO-) has been demonstrated as a biomarker for evaluation and pre-diagnosis of drug-induced liver injury (DILI). In this work, we developed a red-emitting D-π-A type fluorescence probe DIC-NP which was based on 4'-hydroxy-4-biphenylcarbonitrile modified with dicyanoisophorone as a fluorescent reporter and diphenyl phosphinic chloride group as the reaction site for highly selective and sensitive sensing ONOO-. Probe DIC-NP displayed a low detection limit (14.9 nM) and 60-fold fluorescent enhancement at 669 nm in the sensing of ONOO-. Probe DIC-NP was successfully applied to monitor exogenous and endogenous ONOO- in living HeLa cells and zebrafish. Furthermore, we verified the toxicity of isoniazid (INH) and pyrazinamide (PZA) by taking the oxidative stress induced by APAP as a reference, and successfully imaged anti-tuberculosis drug-induced endogenous ONOO- in HepG2 cells. More importantly, we developed a series of mice models of liver injury and investigated the hepatotoxicity caused by the treatment of anti-tuberculosis drugs. At the same time, H&E of mice organs (heart, liver, spleen, lung, kidney) further confirmed the competence of probe DIC-NP for estimating the degree of drug-induced liver injury, which laid a solid foundation for medical research.


Assuntos
Antituberculosos , Doença Hepática Induzida por Substâncias e Drogas , Humanos , Camundongos , Animais , Antituberculosos/toxicidade , Isoniazida/toxicidade , Pirazinamida/toxicidade , Células HeLa , Peixe-Zebra , Corantes Fluorescentes/farmacologia , Ácido Peroxinitroso
11.
Cancer Biomark ; 38(1): 121-130, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37545220

RESUMO

BACKGROUND: Bone metastases affect 50% to 70% of breast cancer (BC) patients and have a high mortality rate. Adipose tissue loss plays a pivotal role in the progression of cancer. OBJECTIVE: This study aims to evaluate the prognostic value of adipose tissue for bone metastasis in BC patients. METHODS: 517 BC patients were studied retrospectively. Patients' characteristics before the surgery were collected. Quantitative measurements of the subcutaneous fat index (SFI) were performed at the level of the eleventh thoracic vertebra. In order to adjust for the heterogeneity between the low SFI and high SFI groups, propensity score matching (PSM) was used. The Kaplan-Meier method was used to estimate the 5-year bone metastatic incidence. The prognostic analysis was performed with the Cox regression models. RESULTS: Compared with the patients without bone metastasis, the patients with bone metastasis had reduced SFI levels. In addition, Kaplan-Meier analysis revealed that patients with low SFI were more likely to develop bone metastases. The independent predictive value of SFI for bone metastases was confirmed by Cox regression analysis. The survival analysis was repeated after PSM with a 1:1 ratio, yielding similar results (P< 0.05). CONCLUSIONS: SFI is an independent predictor of bone metastasis in BC patients.


Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Estudos Retrospectivos , Mama/patologia , Prognóstico , Gordura Subcutânea/patologia
12.
Front Pharmacol ; 14: 1141311, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397496

RESUMO

Acute promyelocytic leukemia (APL) is currently considered a disease with a higher cure rate. And cases of secondary malignant tumors following successful APL treatment are rare. Here we described a rare case of a 29-year-old man who was treated for APL in 2019 and developed BCR-ABL1-positive acute lymphoblastic leukemia 2 years later. The patient responded well to tyrosine kinase inhibitors and chemotherapy, and achieved a molecular remission. Although APL usually has a good prognosis, the prognosis of its secondary malignancies is uncertain. There are no effective measures to prevent the occurrence of secondary tumors. Continuing to increase the monitoring frequency of laboratory tests, especially the molecular biomarkers, is essential for the diagnosis and treatment of secondary malignancies after the patients achieving complete remission.

13.
Clin Oral Investig ; 27(9): 5427-5438, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37480368

RESUMO

OBJECTIVES: This study aimed to compare implant positioning accuracy and patient-centered results between static and dynamic computer-assisted implant surgery (s-CAIS and d-CAIS) in edentulous jaws. MATERIAL AND METHODS: The current study retrospectively evaluated a total of 110 implants placed in 22 fully edentulous patients via s-CAIS or d-CAIS (n = 11). The accuracy of implant positioning was assessed by measuring the implant's angular deviation and deviation at the platform and apex from the preoperative design postoperatively. Patient-centered results, including preoperative and intraoperative patient-reported experiences and postoperative patient-reported outcomes, were extracted from the medical records. The nested t test and chi-square test were used to compare accuracy and patient-centered results between s-CAIS and d-CAIS postoperatively. RESULTS: The implants in the s-CAIS group showed significantly smaller angular deviation (2.32 ± 1.23°) than those in the d-CAIS group (3.87 ± 2.75°). In contrast, the platform and apical deviation were significantly larger in s-CAIS (1.56 ± 1.19 mm and 1.70 ± 1.09 mm, respectively) than d-CAIS (1.02 ± 0.45 mm and 1.00 ± 0.51 mm, respectively). Furthermore, the implants in the s-CAIS group deviated significantly (p < 0.001) more toward the coronal direction than those in the d-CAIS group. Notably, all patients in the s-CAIS group reported an obvious foreign body sensation during surgery, representing a significant difference from the d-CAIS group. CONCLUSIONS: Compared to s-CAIS, d-CAIS is a reliable technique for the placement of multiple implants in fully edentulous patients with less linear deviation and less foreign body sensation. TRIAL REGISTRATION: The retrospective study was registered on the Chinese Clinical Trial Registry on August 8th, 2022, with registration number No. ChiCTR2200062484. CLINICAL RELEVANCE: Despite the increasing use of computer- assisted implant surgery in fully edentulous patients, clinical evidence comparing implant positioning accuracy and patient-centered results between static and dynamic CAIS systems is scarce. Our study demonstrated that compared to s-CAIS, d-CAIS is a reliable technique for the placement of multiple implants in fully edentulous patients with less linear deviation.


Assuntos
Implantes Dentários , Corpos Estranhos , Arcada Edêntula , Boca Edêntula , Humanos , Estudos Retrospectivos , Arcada Edêntula/cirurgia , Boca Edêntula/cirurgia , Assistência Centrada no Paciente , Computadores
14.
Biomed Pharmacother ; 165: 115208, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37499454

RESUMO

Myc target 1 (MYCT1), located at 6q25.2, is a crucial player in cancer development. While widely distributed in cells, its subcellular localization varies across different cancer types. As a novel c-Myc target gene, MYCT1 is subject to regulation by multiple transcription factors. Studies have revealed aberrant expression of MYCT1 in various cancers, impacting pivotal biological processes such as proliferation, apoptosis, migration, genomic instability, and differentiation in cancer cells. Additionally, MYCT1 plays a critical role in modulating tumor angiogenesis and remodeling tumor immune responses within the tumor microenvironment. Despite certain debated functions, MYCT1 undeniably holds significance in cancer development. In this review, we comprehensively examine the relationship between MYCT1 and cancer, encompassing gene structure, regulation of gene expression, gene mutation, and biological function, with the aim of providing valuable insights for cancer diagnosis and treatment.


Assuntos
Neoplasias , Proteínas Nucleares , Proteínas Proto-Oncogênicas c-myc , Linhagem Celular Tumoral , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Humanos , Proteínas Nucleares/genética
15.
Sci Total Environ ; 898: 165350, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37419367

RESUMO

Despite considerable decreases in fine particulate matter (PM2.5) in Chinese megacities over the past decade, many second- and third-tier cities that distribute abundant industrial enterprises are still facing great challenges for PM2.5 further reduction under the recent policy background of eliminating heavily-polluted weather. In view of core effects of NOx on PM2.5, the deeper reductions of NOx in these cities are expected to break the plateau of PM2.5 decline, however, the link between NOx emission and PM2.5 mass loading is currently lacking. Herein, we progressively construct an evaluation system for PM2.5 productions based on daily NOx emissions in a typical industrial city (Jiyuan), considering a sequence of nested parameters involving evolutions of NO2 into nitric acid and then nitrate, and contributions of nitrate to PM2.5. The evaluation system was subsequently validated to better reproduce real increasing processes for PM2.5 pollution based on 19 pollution cases, with root mean square errors of 19.2 ± 16.4 %, suggesting the feasibility of developing NOx emission indicators linked to goals of mitigating atmospheric PM2.5. Additionally, further comparative results reveal that currently high NOx emissions in this industrial city severely hinder the achievement of atmospheric PM2.5 environmental capacity targets, especially in the scenarios of high initial PM2.5 level, low planetary boundary layer height and long pollution duration. It is anticipated that these methodologies and findings would supply guidelines for further regional PM2.5 mitigation, in which source-oriented NOx indicators could also provide some orientations for industrial cleaner production such as denitrification and low nitrogen combustion.

16.
Foods ; 12(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37238785

RESUMO

High temperatures applied in the production of plant-based meat analogs (PBMA) lead to the occurrence of Maillard reactions, in which harmful compounds Nε-(carboxymethyl)lysine (CML), Nε-(carboxyethyl)lysine (CEL) and acrylamide are formed. However, little research has focused on these compounds in PBMA. In this study, the contents of CML, CEL and acrylamide in 15 commercial-sold PBMA were determined by an ultra-high performance liquid chromatograph coupled with a triple quadrupole tandem mass spectrometer (UHPLC-QqQ-MS/MS). Nutrients (protein, amino acids, fatty acids and sugars) which are related to the formation of these compounds were also studied. The results showed that CML, CEL and acrylamide contents were in the range of 16.46-47.61 mg/kg, 25.21-86.23 mg/kg and 31.81-186.70 µg/kg, respectively. Proteins account for 24.03-53.18% of PBMA. Except for Met + Cys, which is the limiting amino acid of most PBMA, all other indispensable amino acids met the requirements for adults. Besides, PBMA had more n-6 fatty acids than n-3 fatty acids. A correlation analysis showed that proteins and the profiles of amino acid and fatty acid had little influence on CML but significant influence on CEL and acrylamide. The results of the present study can be used as a reference to produce PBMA with higher amounts of nutrients and lower amounts of CML, CEL and acrylamide.

17.
J Orthop Surg Res ; 18(1): 304, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37069639

RESUMO

OBJECTIVE: Osteoporosis (OP) is a disease caused by multiple factors. Studies have pointed out that isopsoralen (IPRN) is one of the most effective drugs for the treatment of OP. Based on network pharmacological and molecular experimental analysis, the molecular mechanism of IPRN in osteoporosis is clarified. METHODS: IPRN target genes and OP-related genes were predicted from the databases. Intersections were obtained and visualized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on target genes, which was confirmed by experiments internal and external experiments. Molecular docking was used to verify the binding between IPRN and target proteins. Molecular dynamics (MD) simulates the binding affinity of protein targets and active compounds. RESULTS: 87 IPRN target genes and 242 disease-related targets were predicted. The protein-protein interaction (PPI) network identified 18 IPRN target proteins for the treatment of OP. GO analysis indicated that target genes were involved in biological processes. KEGG analysis showed that pathways such as PI3K/AKT/mTOR were associated with OP. Cell experiments (qPCR and WB) found that the expressions of PI3K, AKT, and mTOR in MC3T3-E1 cells at 10 µM, 20 µM, and 50 µM IPRN concentrations, especially at 20 µM IPRN treatment, were higher than those in the control group at 48 h. Animal experiments also showed that compared with the control group, 40 mg/kg/time IPRN could promote the expression of the PI3K gene in chondrocytes of SD rats. CONCLUSIONS: This study predicted the target genes of IPRN in the treatment of OP and preliminarily verified that IPRN plays an anti-OP role through the PI3K/AKT/mTOR pathway, which provides a new drug for the treatment of OP.


Assuntos
Medicamentos de Ervas Chinesas , Osteoporose , Animais , Ratos , Ratos Sprague-Dawley , Farmacologia em Rede , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt , Osteoporose/tratamento farmacológico , Osteoporose/genética
19.
Discov Med ; 35(174): 28-35, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37024439

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) AP000695.2 (ENSG00000248538) expresses abnormally in various malignancies, what shows its role as oncogene. However, it has not been extensively studied in gastric cancer. The aim of the current study was to explore the clinical value of AP000695.2 to prognose gastric cancer. METHODS: The cancer genome atlas (TCGA) and the gene expression profiling interactive analysis (GEPIA) online tool were used to analyze AP000695.2 expression pattern, diagnostic and prognostic role in gastric cancer. Kaplan-Meier and Cox regression analyses were used to assess survival in patients with gastric cancer. Receiver operating curve (ROC) analysis was used to assess AP000695.2 diagnostic capacity. Nomograms were created to predict overall survival (OS) and progression free survival (PFS). RESULTS: LncRNA AP000695.2 was abnormally upregulated in 19 types of malignancy, including gastric cancer. Survival analysis indicated that high expression of AP000695.2 was associated with poor survival of gastric cancer. Multivariate Cox regression analysis verified the independent prognostic value of AP000695.2 to predict OS (HR (hazard ratio): 1.104, 95% CI (confidence interval): 1.035-1.178, p = 0.003) and PFS (HR: 1.170, 95% CI: 1.090-1.256, p < 0.001). ROC analysis indicated a favorable AP000695.2 diagnostic capacity (area under the curve (AUC) = 0.890). Nomograms were also constructed for OS and PFS based on AP000695.2 expression-related risk score. Additionally, AP000695.2 was found to be positively associated with tumor-infiltrating immune cells, including classically activated (M1) macrophages, neutrophils, alternatively activated (M2) macrophages, and natural killer (NK) cells. CONCLUSIONS: It was observed that AP000695.2 can be used as a novel biomarker to diagnose or predict survival of gastric patient.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Estimativa de Kaplan-Meier , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
20.
Nat Methods ; 20(3): 459-468, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36823335

RESUMO

Single-molecule localization microscopy in a typical wide-field setup has been widely used for investigating subcellular structures with super resolution; however, field-dependent aberrations restrict the field of view (FOV) to only tens of micrometers. Here, we present a deep-learning method for precise localization of spatially variant point emitters (FD-DeepLoc) over a large FOV covering the full chip of a modern sCMOS camera. Using a graphic processing unit-based vectorial point spread function (PSF) fitter, we can fast and accurately model the spatially variant PSF of a high numerical aperture objective in the entire FOV. Combined with deformable mirror-based optimal PSF engineering, we demonstrate high-accuracy three-dimensional single-molecule localization microscopy over a volume of ~180 × 180 × 5 µm3, allowing us to image mitochondria and nuclear pore complexes in entire cells in a single imaging cycle without hardware scanning; a 100-fold increase in throughput compared to the state of the art.


Assuntos
Aprendizado Profundo , Imageamento Tridimensional/métodos , Imagem Individual de Molécula/métodos
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