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1.
Drug Dev Ind Pharm ; : 1-13, 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37158661

RESUMO

OBJECTIVE: The drooping process of the Xuesaitong dropping pills (XDPs) was optimized based on quality by design concept. Meanwhile, a machine vision (MV) technology was creatively introduced in this study to predict the critical quality attributes (CQAs) rapidly and accurately. SIGNIFICANCE: This study improves the understanding of dropping process, and has reference value for the guidance of pharmaceutical process research and industrial production. METHODS: The study mainly consisted of three stages: the first stage involved the prediction model to establish and evaluate the CQAs, and the second stage involved assessing the quantitative relationships between critical process parameters (CPPs) and CQAs by the mathematical models that were established through the Box-Behnken experimental design. Finally, a probability-based design space for the dropping process was calculated and verified according to the qualification criteria of each quality attribute. RESULTS: The results show that the prediction accuracy of the random forest (RF) model was high and met the analysis requirements, and the CQAs of dropping pills can meet the standard by running in the design space. CONCLUSION: The MV technology developed in this study can be applied to the optimization process of the XDPs. In addition, the operation in the design space can not only ensure the quality of XDPs to meet the criteria, but also help to improve the consistency of XDPs.

2.
Theor Appl Genet ; 136(6): 129, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37193909

RESUMO

KEY MESSAGE: A soybean natural population genotyped by resequencing and another RIL population genotyped by SoySNP6K were used to explore consistent genetic loci and genes under greenhouse- and field-conditions for SMV-SC8 resistance. Soybean mosaic virus (SMV) is a member of the genus Potyvirus that occurs in all soybean-growing areas of the world and causes serious losses of yield and seed quality. In this study, a natural population composed of 209 accessions resequenced at an average depth of 18.44 × and another RIL population containing 193 lines were used to explore genetic loci and genes conferring resistance to SMV-SC8. There were 3030 SNPs significantly associated with resistance to SC8 on chromosome 13 in the natural population, among which 327 SNPs were located within an ~ 0.14 Mb region (from 28.46 to 28.60 Mb) of the major QTL qRsc8F in the RIL population. Two genes among 21 candidate genes, GmMACPF1 and GmRad60, were identified in the region of consistent linkage and association. Compared to the mock control, the changes in the expression of these two genes after inoculation with SC8 differed between resistant and susceptible accessions. More importantly, GmMACPF1 was shown to confer resistance to SC8 by significantly decreasing virus content in soybean hairy roots overexpressing this gene. A functional marker, FMSC8, was developed based on the allelic variation of GmMACPF1, and a high coincidence rate of 80.19% between the disease index and marker genotype was identified in the 419 soybean accessions. The results provide valuable resources for studies on the molecular mechanism of SMV resistance and genetic improvement in soybean.


Assuntos
Potyvirus , Soja , Mapeamento Cromossômico , Soja/genética , Potyvirus/genética , Loci Gênicos , Doenças das Plantas/genética , Resistência à Doença/genética
3.
Sci Total Environ ; 887: 164110, 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37178851

RESUMO

1,3-Diphenylguanidine (DPG), benzothiazole (BTH), benzotriazole (BTR), and their derivatives are high-production-volume chemicals widely used in tires, corrosion inhibitors and plastic products. Vehicular traffic is an important source of these chemicals in the environment. Despite this, little is known about the occurrence of these chemicals in roadside soils. In this study, we determined the concentrations, profiles, and distribution patterns of 3 DPGs, 5 BTHs, and 7 BTRs in 110 soil samples collected from northeastern United States. We found widespread occurrence of 12 out of the 15 analytes measured in roadside soils, at detection frequencies ≥71 % and median concentrations in the range of 0.38-380 ng/g (dry weight). DPGs were the predominant chemicals accounting for 63 % of the sum concentrations of three chemical classes determined, followed by BTHs (28 %) and BTRs (9 %). The concentrations of all analytes (except for 1-, 4-, and 5-OH-BTRs) exhibited significant positive correlations (r: 0.1-0.9, p < 0.01), suggestive of their common sources and/or similar environmental fates. Higher concentrations of DPGs, BTHs and BTRs were found in soils from highways, rubberized playgrounds, and indoor parking lots than those from gardens, parks, and residential areas. Our findings suggest the release of DPGs, BTHs and BTRs from rubber products, especially automobile tires. Further studies are needed to investigate the environmental fate and toxicities of these chemicals to humans and wildlife.

4.
BMC Ophthalmol ; 23(1): 193, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37131213

RESUMO

BACKGROUND: To evaluate anterior segment structural alterations after implantable collamer lens (ICL) implantation in myopic patients using swept-source quantitative optical coherence tomography (SS-OCT). METHODS: This prospective study included 47 eyes in 24 patients with preoperative spherical equivalent ≥ -3.00 D. Patients underwent ICL implantation at Department of Ophthalmology, Peking University Third Hospital, from May 2021 to December 2022. SS-OCT was used to measure anterior chamber width (ACW), angle opening distance (AOD), angle recess area (ARA), trabecular-iris area (TISA), trabecular-iris angle (TIA), iridotrabecular contact (ITC) area, and ITC Index before ICL implantation surgery and at 1 month follow-up. The correlations among the ITC index, vault, and angle parameters were analysed. Receiver operating characteristic (ROC) analysis was used to explore the ability of the vault to identify eyes with suspected angle-closure. RESULTS: At one month following ICL implantation, the ITC area was 0.396 ± 0.37 mm2, and the ITC index is 8.143 ± 5.439%. All angle parameters, except ACW, showed a statistically significant reduction on SS-OCT (P < 0.05). Mean AOD500, AOD750, ARA500, ARA750, TISA500, TISA750, TIA500, and TIA750 values at one month postoperatively decreased by 60.0%, 60.4%, 58.1%, 59.2%, 57.3%, 58.7%, 48.8%, and 50.7%, respectively. The vault was positively correlated with the ITC index and percent change in anterior chamber angle parameters. A vault of > 0.659 mm was found to be optimal for angle-closure suspect with a sensitivity of 85.2% and a specificity of 53.9%. CONCLUSIONS: Anterior chamber angle parameters decreased one month after ICL implantation, and their percentage changes and ITC index correlated with the vault. When the vault is larger than 0.659 mm, it is necessary to be alert to possible closed angle suspicion.


Assuntos
Glaucoma de Ângulo Fechado , Lentes Intraoculares , Humanos , Tomografia de Coerência Óptica/métodos , Estudos Prospectivos , Glaucoma de Ângulo Fechado/diagnóstico , Glaucoma de Ângulo Fechado/cirurgia , Iris/diagnóstico por imagem , Iris/cirurgia , Biometria , Segmento Anterior do Olho/diagnóstico por imagem , Pressão Intraocular , Gonioscopia
5.
Environ Res ; 228: 115874, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37044165

RESUMO

The global consensus is to reduce greenhouse gas emissions and actively respond to climate change (CC). Global warming has irreversibly altered the Earth's ecosystems. Unpredictable extreme weather events caused by CC are posing new risks to urban infrastructure. Infrastructure is one of the primary guarantees to maintain the stable operation of the city. Therefore, it is imperative to strengthen the climate resilience of infrastructure to avoid the loss of life and property caused by climate risks. This paper uses CiteSpace to analyze data in the field of climate resilience infrastructure (CRI) over the past 25 years. We find that global CRI research has transitioned through three stages. According to the geographic spatial distribution map drawn by ArcGIS, it can be found that developed countries account for a relatively large number of documents. The research institution is dominated by institutions of higher learning, with limited cooperation between institutions and loose organizational collaboration. CRI is composed of multi-disciplinary collaborative development, from a single discipline of environmental ecology or water resources to a research field integrating engineering, meteorology, sustainability, and energy. Urban resilience and Nature-based solutions are research hotspots. Small Island Developing States are major objects in the future. The research emphasis has shifted from addressing the multiple problems caused by CC to increasing the climate resilience of infrastructure to enhance the resistance of urban systems. Renewable energy and climate models are applied to infrastructure construction. In general, CRI is a effective measure that can help reduce environmental pollution, carbon emissions, and global climate regulation. In addition, we suggest taking cities as pilot projects in the future, increasing CRI projects and providing policy guidance for urban planning and construction.


Assuntos
Ecossistema , Gases de Efeito Estufa , Cidades , Mudança Climática , Ecologia
6.
J Biol Inorg Chem ; 28(4): 421-437, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37097484

RESUMO

A new ligand DFIP (2-(dibenzo[b,d]furan-3-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) and its two complexes iridium(III) [Ir(ppy)2(DFIP)](PF6) (ppy = 2-phenylpyridine, Ir1) and ruthenium(II) [Ru(bpy)2(DFIP)](PF6)2 (bpy = 2,2'-bipyridine, Ru1) were synthesized and characterized. The anticancer effects of the two complexes on A549, BEL-7402, HepG2, SGC-7901, HCT116 and normal LO2 cells were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Complex Ir1 shows high cytotoxic activity on A549, BEL-7402, SGC-7901 and HepG2, Ru1 exhibits moderate anticancer activity toward A549, BEL-7402 and SGC-7901 cells. The IC50 values of Ir1 and Ru1 toward A549 are 7.2 ± 0.1 and 22.6 ± 1.4 µM, respectively. The localization of complexes Ir1 and Ru1 in the mitochondrial, intracellular accumulation of reactive oxygen species (ROS) levels, and the changes of mitochondrial membrane potential (MMP) and cytochrome c (cyto-c) were investigated. Apoptosis and cell cycle were detected by flow cytometry. Immunogenic cell death (ICD) was used to detect the effects of Ir1 and Ru1 on the A549 using a confocal laser scanning microscope. The expression of apoptosis-related proteins was detected by western blotting. Ir1 and Ru1 can increase the intracellular ROS levels and release cyto-c, reduce the MMP, leading to the apoptosis of A549 cells and blocking the A549 cells at the G0/G1 phase. Additionally, the complexes caused a decrease of the expression of polyADP-ribose polymerase (PARP), caspase 3, Bcl-2 (B-cell lymphoma-2), PI3K (phosphoinositide-3 kinase) and upregulated the expression of Bax. All these findings indicated that the complexes exert anticancer efficacy to induce cell death through immunogenic cell death, apoptosis, and autophagy.


Assuntos
Antineoplásicos , Complexos de Coordenação , Rutênio , Humanos , Células A549 , Linhagem Celular Tumoral , Rutênio/farmacologia , Rutênio/química , Irídio/farmacologia , Irídio/química , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Antineoplásicos/química , Complexos de Coordenação/química , Proliferação de Células
7.
Environ Sci Pollut Res Int ; 30(25): 67290-67302, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37103698

RESUMO

Nitrogen-rich organic polymer poly(chloride triazole) (PCTs) was synthesized by a one-step method as metal-halogen-free heterogeneous catalyst for the solvent-free CO2 cycloaddition. PCTs had abundant nitrogen sites and hydrogen bond donors, exhibited great activity for the cycloaddition of CO2 and epichlorohydrin, and achieved 99.6% yield of chloropropene carbonate under the conditions of 110 ℃, 6 h, and 0.5 MPa CO2. The activation of epoxides and CO2 by hydrogen bond donor and nitrogen sites was further explained by density functional theory (DFT) calculations. In summary, this study showed that nitrogen-rich organic polymer is a versatile platform for CO2 cycloaddition, and this paper provides a reference for the design of CO2 cycloaddition catalysts.


Assuntos
Dióxido de Carbono , Polímeros , Reação de Cicloadição , Dióxido de Carbono/química , Polímeros/química , Catálise , Compostos de Epóxi/química
8.
Electrophoresis ; 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37029336

RESUMO

The aim of this study was to establish a rapid quality assessment method for Gentianae Macrophyllae Radix (RGM) using near-infrared (NIR) spectra combined with chemometric analysis. The NIR spectra were acquired using an integrating sphere diffuse reflectance module, using air as the reference. Capillary electrophoresis (CE) analyses were performed on a model P/ACE MDQ Plus system. Partial least squares-discriminant analysis qualitative model was developed to distinguish different species of RGM samples, and the prediction accuracy for all samples was 91%. The CE response values at each retention time were predicted by building a partial least squares regression (PLSR) calibration model with the CE data set as the Y matrix and the NIR spectra data set as the X matrix. The converted CE fingerprints basically match the real ones, and the six main peaks can be accurately predicted. Transforming NIR spectra fingerprints into the form of CE fingerprints increases its interpretability and more intuitively demonstrates the components that cause diversity among samples of different species and origins. Loganic acid, gentiopicroside, and roburic acid were considered quality indicators of RGM and calibration models were built using PLSR algorithm. The developed models gave root mean square error of prediction of 0.2592% for loganic acid, 0.5341% for gentiopicroside, and 0.0846% for roburic acid. The overall results demonstrate that the rapid quality assessment system can be used for quality control of RGM.

9.
Pharmacol Res ; 190: 106724, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36907287

RESUMO

Organic anion transporting polypeptide 2B1 (OATP2B1/SLCO2B1) facilitates uptake transport of structurally diverse endogenous and exogenous compounds. To investigate the roles of OATP2B1 in physiology and pharmacology, we established and characterized Oatp2b1 knockout (single Slco2b1-/- and combination Slco1a/1b/2b1-/-) and humanized hepatic and intestinal OATP2B1 transgenic mouse models. While viable and fertile, these strains exhibited a modestly increased body weight. In males, unconjugated bilirubin levels were markedly reduced in Slco2b1-/- compared to wild-type mice, whereas bilirubin monoglucuronide levels were modestly increased in Slco1a/1b/2b1-/- compared to Slco1a/1b-/- mice. Single Slco2b1-/- mice showed no significant changes in oral pharmacokinetics of several tested drugs. However, markedly higher or lower plasma exposure of pravastatin and the erlotinib metabolite OSI-420, respectively, were found in Slco1a/1b/2b1-/- compared to Slco1a/1b-/- mice, while oral rosuvastatin and fluvastatin behaved similarly between the strains. In males, humanized OATP2B1 strains showed lower conjugated and unconjugated bilirubin levels than control Slco1a/1b/2b1-deficient mice. Moreover, hepatic expression of human OATP2B1 partially or completely rescued the impaired hepatic uptake of OSI-420, rosuvastatin, pravastatin, and fluvastatin in Slco1a/1b/2b1-/- mice, establishing an important role in hepatic uptake. Expression of human OATP2B1 in the intestine was basolateral and markedly reduced the oral availability of rosuvastatin and pravastatin, but not of OSI-420 and fluvastatin. Neither lack of Oatp2b1, nor overexpression of human OATP2B1 had any effect on fexofenadine oral pharmacokinetics. While these mouse models still have limitations for human translation, with additional work we expect they will provide powerful tools to further understand the physiological and pharmacological roles of OATP2B1.


Assuntos
Bilirrubina , Transportadores de Ânions Orgânicos , Masculino , Camundongos , Humanos , Animais , Rosuvastatina Cálcica , Fluvastatina , Pravastatina , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos/metabolismo , Camundongos Transgênicos , Peptídeos/metabolismo , Ânions/metabolismo , Camundongos Knockout
10.
Int J Mol Sci ; 24(6)2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36982472

RESUMO

Improvement in acid phosphatase (APase) activity is considered as an important approach to enhance phosphorus (P) utilization in crops. Here, GmPAP14 was significantly induced by low P (LP), and its transcription level in ZH15 (P efficient soybean) was higher than in NMH (P inefficient soybean) under LP conditions. Further analyses demonstrated that there were several variations in gDNA (G-GmPAP14Z and G-GmPAP14N) and the promoters (P-GmPAP14Z and P-GmPAP14N) of GmPAP14, which might bring about differential transcriptional levels of GmPAP14 in ZH15 and NMH. Histochemical staining measurements revealed that a stronger GUS signal was present in transgenic Arabidopsis with P-GmPAP14Z under LP and normal P (NP) conditions compared with the P-GmPAP14N plant. Functional research demonstrated that transgenic Arabidopsis with G-GmPAP14Z had a higher level of GmPAP14 expression than the G-GmPAP14N plant. Meanwhile, higher APase activity was also observed in the G-GmPAP14Z plant, which led to increases in shoot weight and P content. Additionally, validation of variation in 68 soybean accessions showed that varieties with Del36 displayed higher APase activities than the del36 plant. Thus, these results uncovered that allelic variation in GmPAP14 predominantly altered gene expression to influence APase activity, which provided a possible direction for research of this gene in plants.


Assuntos
Arabidopsis , Fosfatase Ácida/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Expressão Gênica , Regulação da Expressão Gênica de Plantas , Fósforo/metabolismo , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Soja/genética , Soja/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
11.
Electrophoresis ; 44(9-10): 793-806, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36787349

RESUMO

In this study, the capillary electrophoresis-photodiode array detector was employed for the analysis of four iridoid compounds in Gentiana macrophylla Radix (RGM), and the method was optimized based on the concept of analytical quality by design (AQbD). The peak areas relative standard deviation (n = 3) and resolution of the four analytes were selected as critical method attributes. Fractional factorial design test combined with Pareto analysis were employed to screen critical method parameters (buffer concentration, pH, sodium dodecyl sulfate [SDS] micelle concentration, temperature, and voltage). Subsequently, three main factors (buffer concentration, buffer pH, and SDS concentration) were selected by central composite design test for constructing the design space. The optimal separation conditions as follows: capillary column (50.2 cm × 50 µm, detection length 40 cm). Working background electrolyte consisted of 51 mmol/L borax solution (pH = 9.47) and 40 mmol/L SDS. The samples were injected by pressure (5 s at 0.5 psi) and the detection was performed at 254 nm. Applied voltage was 20 kV and column temperature was 23°C. The developed method is rapid and reliable for the quantitative analysis of four iridoid compounds in RGM, providing a reference for the application of AQbD concept in the analysis of natural products.


Assuntos
Medicamentos de Ervas Chinesas , Gentiana , Iridoides , Eletroforese Capilar/métodos , Raízes de Plantas/química , Medicamentos de Ervas Chinesas/análise
12.
Nature ; 614(7948): 456-462, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36792740

RESUMO

Stretchable hybrid devices have enabled high-fidelity implantable1-3 and on-skin4-6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans7,8 and soft robots9,10, rigid modules containing Si-based microelectronics11,12 and protective encapsulation modules13,14. To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure15-17. Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft-soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm-1. As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices.


Assuntos
Eletromiografia , Eletrônica Médica , Nanoestruturas , Maleabilidade , Polímeros , Próteses e Implantes , Dispositivos Eletrônicos Vestíveis , Humanos , Nanoestruturas/química , Polímeros/química , Pele , Monitorização Fisiológica , Eletrônica Médica/instrumentação , Eletrônica Médica/métodos , Eletromiografia/instrumentação
13.
J Pharm Biomed Anal ; 228: 115294, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-36827860

RESUMO

Hippocampus histrix Kaup is a popular marine medicine with high medicinal and healthcare values. In this study, liquid chromatography-mass spectrometry (LC-MS) analysis combined with network pharmacological method was used to screen for suitable quantitative indicators for the quality control of H. histrix Kaup. Firstly, an LC-MS analytical method for the simultaneous determination of 12 nucleosides in extracts of H. histrix Kaup was established. And then, a network pharmacological method incorporated target prediction, protein-protein interaction network, components-targets network, and targets-pathways network was performed to screen for quantitative indicators. Finally, the developed LC-MS method was transferred to liquid chromatographs to improve the generalizability of the method. All 12 nucleotides were authenticated in extracts of H. histrix Kaup by comparing with the standards. The optimal chromatographic separation conditions are as follows: the chromatographic separation was achieved on an Acquire BEH-C18 column (2.1 mm * 100 mm, 1.7 µm) and gradient elution was performed using methanol solution and buffer (0.30% formic acid and 10 mmol/L ammonium acetate) as mobile phase at a flow rate of 0.15 mL/min and an acquisition wavelength of 260 nm. Network pharmacology results showed that adenosine, and uridine show excellent pharmacological activity. Integration the content, correlation, chromatographic separation, and pharmacological activity of each compound in H. histrix Kaup, uridine and adenosine were tentatively determined as quantitative indicators for quality control in H. histrix Kaup. The established LC-MS method was successfully transferred to liquid chromatographs, and the method is stable and reliable for the quality control of H. histrix Kaup. This developed integrated strategy was successfully used to screen quantitative indicators in the H. histrix Kaup.


Assuntos
Smegmamorpha , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Farmacologia em Rede , Adenosina/farmacologia , Uridina , Cromatografia Líquida de Alta Pressão/métodos
15.
Biol Chem ; 404(6): 633-643, 2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-36632703

RESUMO

Dipeptidyl peptidases constitute a class of non-classical serine proteases that regulate an array of biological functions, making them pharmacologically attractive enzymes. With this work, we identified and characterized a dipeptidyl peptidase from Mycobacterium tuberculosis (MtDPP) displaying a strong preference for proline residues at the P1 substrate position and an unexpectedly high thermal stability. MtDPP was also characterized with alanine replacements of residues of its active site that yielded, for the most part, loss of catalysis. We show that MtDPP catalytic activity is inhibited by well-known human DPP4 inhibitors. Using MALDI-TOF mass spectrometry we also describe that in vitro, MtDPP mediates the truncation of the C-X-C motif chemokine ligand 10, indicating a plausible role in immune modulation for this mycobacterial enzyme.


Assuntos
Dipeptidil Peptidases e Tripeptidil Peptidases , Mycobacterium tuberculosis , Humanos , Mycobacterium tuberculosis/metabolismo , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/metabolismo , Peptídeos , Serina Endopeptidases/metabolismo , Especificidade por Substrato
16.
J Inorg Biochem ; 241: 112134, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36706490

RESUMO

In this study, two new iridium(III) polypyridyl complexes [Ir(bzq)2(DIPH)](PF6) (bzq = deprotonated benzo[h]quinoline, DIPH = 4-(2,5-dibromo-4-(1H-imidazo[4,5-f][1,10]phenanthrolim-2-yl)-4-hydroxybutan-2-one) (Ir1) and [Ir(piq)2(DIPH)](PF6) (piq = deprotonated 1-phenylisoquinoline) (Ir2) were synthesized and characterized by elemental analysis, HRMS, 1H and 13C NMR. The cytotoxic activity of Ir1, Ir2, Ir1lipo and Ir2lipo against cancer cells SGC-7901, HepG2, A549, HeLa, B16 and normal NIH3T3 cells in vitro was evaluated using 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. Ir1 and Ir2 showed no cytotoxic activity, but their liposome-entrapped Ir1 (Ir1lipo) and Ir2 (Ir2lipo) showed significant cellular activity, especially sensitive to SGC-7901 with IC50 values of 4.7 ± 0.2 and 12.4 ± 0.5 µM, respectively. The cellular uptake, endoplasmic reticulum (ER) localization, autophagy, tubulin polymerization, glutathione (GSH), malondialdehyde (MDA) and release of cytochrome c were investigated to explore the mechanisms of apoptosis. The calreticulin (CRT), heat shock protein 70 (HSP70), high mobility group box 1 (HMGB1) were also explored. Western blotting showed that Ir1lipo and Ir2lipo inhibited PI3K (phosphoinositide-3 kinase), AKT (protein kinase B), p-AKT and activated Bcl-2 (B-cell lymphoma-2) protein and apoptosis-regulated factor caspase 3 (cysteinyl aspartate specific proteinase-3) and cleaving PARP (poly ADP-ribose polymerase). The results demonstrated that Ir1lipo and Ir2lipo induce cell apoptosis through targeting the endoplasmic reticulum (ER), cause oxidative stress damage, inhibiting PI3K/AKT signaling pathway, immunogenic cell death (ICD) and inhibit the cell growth at G2/M phase.


Assuntos
Antineoplásicos , Complexos de Coordenação , Camundongos , Animais , Humanos , Linhagem Celular Tumoral , Lipossomos/farmacologia , Irídio/química , Proteínas Proto-Oncogênicas c-akt , Complexos de Coordenação/química , Células NIH 3T3 , Fosfatidilinositol 3-Quinases , Proliferação de Células , Antineoplásicos/farmacologia , Apoptose
17.
Orthop Surg ; 15(3): 731-739, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36625784

RESUMO

OBJECTIVE: At present, there is no consensus or guidance on indications for osteonecrosis of the femoral head (ONFH) patients to receive hip arthroplasty (THA) treatment. This study aims to explore the factors that influence the decision-making for THA in patients with ONFH, and to provide references for clinical decision for ONFH patients to be indicated for THA or hip preservation. METHODS: This retrospective case-control study involved data for ONFH patients from July 2016 to October 2021 from the China Osteonecrosis of the Femoral Head Database (CONFHD). The patients with ONFH, and unilateral hip affected at the first visit were divided into THA group and non-THA group according to if they had undergone THA treatment. The differences between the two groups of patients in terms of gender, age at the time of consultation, body mass index (BMI), etiology, onset side, association research circulation osseous (ARCO) stage, hip joint function, visual analog scale (VAS), etc. were analyzed. Multivariate binomial logistic regression analysis was then applied to evaluate the risk factors of ONFH patients who underwent THA during the first visit. RESULTS: A total of 640 patients were recruited for analysis, including 209 cases from the THA group and 431 cases from the non-THA group. The results of univariate analysis showed that the two groups of patients were significantly different in the following six indicators: age (59 vs. 46, Z = -9.58, p < 0.001), duration of disease (78 vs. 17, Z = -16.14, p < 0.001), gender composition (χ2  = 8.09, p = 0.004), disease etiology (χ2  = 33.04, p < 0.001), ARCO stage (χ2  = 334.86, p < 0.001), flexion of hip joint (χ2  = 172.33, p < 0.001). However, the comparison between the two groups on VAS (Z = -0.82, p = 0.41), BMI (Z = -1.35, p = 0.18), and onset side (χ2  = 1.53, p = 0.22) did not obviously differ. The results regression analysis showed that the age at the time of consultation, duration of disease, ARCO stage, and the hip joint function affected the decision making if the patients should undergo THA. The results of receiver operating characteristic curve (ROC) analysis showed that aforementioned indicators were satisfactory in predicting whether patients with ONFH would be treated with THA. The regression model using the above four indicators as comprehensive indicators has satisfactory performance in predicting whether to perform THA, and the area under the curve (AUC) is 93.94%. CONCLUSION: These factors such as age, duration of disease, ARCO stage, and hip flexion function should be considered comprehensively before making decisions to perform THA or not in our clinical practice.


Assuntos
Artroplastia de Quadril , Necrose da Cabeça do Fêmur , Humanos , Artroplastia de Quadril/métodos , Estudos Retrospectivos , Estudos de Casos e Controles , Cabeça do Fêmur/cirurgia , Resultado do Tratamento , Necrose da Cabeça do Fêmur/cirurgia , China
18.
Environ Sci Pollut Res Int ; 30(14): 39695-39707, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36598728

RESUMO

The renovation problem of old residential areas is not only a city management task, but also a major engineering of benefiting the people, which is related to the people living and working in peace and contentment and the improvement of the overall image of the city. In order to improve the appearance of old residential areas in Chinese cities and the living conditions of their residents, city planners must take a scientific and structured approach to renovation. After analyzing current status of the old residential in several major Chinese cities, consulting the literature, and undertaking field investigations, this paper summarizes the main influencing factors on renovation decision-making. We propose five hypotheses, which we test using questionnaire survey data, sample analysis of these influencing factors, and a structural equation model (SEM). The results show that the degree of influence of each factor on renovation decisions ranks as technology being the most influential, followed by the economy, policy, the environment, and society. In addition, we find that there is nonzero correlation between these various factors.


Assuntos
Modelos Teóricos , Desenvolvimento Sustentável , Humanos , Cidades , Inquéritos e Questionários , Tecnologia , China
19.
Environ Sci Technol ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633507

RESUMO

Recently, a study found that aromatic DBP fractions dominate the overall toxicity of chlorinated drinking water. However, key toxicity drivers have not been reported via comprehensive evaluation based on the formation of aliphatic and aromatic DBPs in drinking water. In this study, the occurrence of 37 aliphatic and 19 aromatic DBPs in drinking samples with different water characteristics collected in a Chinese megacity was explored. According to the individual DBP concentrations and cytotoxicity potencies as well as the "TIC-Tox" method, haloacetonitriles and halonitrophenols were found to be the toxicity drivers among the measured aliphatic and aromatic DBPs, respectively. However, when aromatic and aliphatic DBPs are taken into consideration together, aliphatic DBPs were calculated to present higher toxicity contribution than aromatic DBPs, which is inconsistent with the previous study. TOX showed significant positive correlations with most aliphatic DBPs but no aromatic DBPs, and the overall toxicity of the water sample concentrates is significantly related to the total calculated cytotoxicity and aliphatic DBPs, suggesting that current selected aromatic DBPs are insufficient to represent the overall aromatic DBPs. UV254 and DOC rather than SUVA are better surrogates for predicting DBP formation potential for DOM with a lower humification degree as indicated by fluorescence results.

20.
Food Res Int ; 163: 112192, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36596130

RESUMO

To achieve the goals of rapid content determination of capsaicin and adulteration detection of pepper powder. The method based on the hand-held near-infrared spectrometer combined with ensemble preprocessing was proposed. DoE-based ensemble preprocessing technique was utilized to develop the partial least squares regression models of red pepper [Capsicum annuum L. var. conoides (Mill.) Irish] powders. The performance of final models was evaluated using coefficient of determination (R2), root mean square error of prediction (RMSEP) and residual predictive deviation (RPD). Model development using selective ensemble preprocessing gave the best prediction of capsaicin in Yanjiao pepper powder (R2 = 0.9800, RPD = 7.090, RMSEP = 0.00689) and Tianying pepper powder (R2 = 0.8935, RPD = 3.017, RMSEP = 0.06154). Moreover, the potential of grey wolf optimizer-support vector machine (GWO-SVM) to detect adulterated pepper powder was investigated. The samples were composed of two authentic products and three different adulterants with different adulteration levels. The results showed that the classification accuracy of GWO-SVM model for Yanjiao peppers was over 90 %, which realized the adulteration detection of Yanjiao pepper. And GWO-SVM showed better performance in detecting adulterated Tianying pepper compared to hierarchical cluster analysis, orthogonal partial least squares discriminant analysis and random forest. In summary, the quality control strategy established in this paper can provide a solution for the adulteration detection and quality evaluation of pepper powder in a rapid and on-site way.


Assuntos
Capsaicina , Capsicum , Pós/análise , Alimentos , Análise dos Mínimos Quadrados
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