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2.
Spectrochim Acta A Mol Biomol Spectrosc ; 278: 121326, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35561446

RESUMO

Hyperuricemia is closely related to a variety of diseases and has been listed as one of the twenty most persistent diseases in the 21st century by the United Nations. Therefore, strengthening the diagnosis of hyperuricemia has become imperative. Here, ordered inverse opal array structures (PAANs) composed of PDMS and gold nanoparticles (AuNPs) have been designed using a bottom-up self-assembly method. The structures exhibit a periodic distribution of hot spots, an enhancement factor (EF) of 4.22 × 104, and a relative standard deviation (RSD) of signal intensity of less than 5%, which can provide high reproducibility of SERS signals. The PAANs substrate is used to detect uric acid in the tears of patients with hyperuricemia, and the limit of detection is 6.03 µM. The significant linear relationship between blood uric acid and tear uric acid indicates that the developed method is a rapid, effective, and non-invasive technique for the determination of uric acid in tears.

3.
Nat Med ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551292

RESUMO

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D (n = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was -1.02% (-1.11, -0.93) in the dorzagliatin group and -0.36% (-0.45, -0.26) in the placebo group (estimated treatment difference, -0.66%; 95% CI: -0.79, -0.53; P < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile ( NCT03141073 ).

4.
Nat Med ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551294

RESUMO

Improving glucose sensitivity remains an unmet medical need in treating type 2 diabetes (T2D). Dorzagliatin is a dual-acting, orally bioavailable glucokinase activator that enhances glucokinase activity in a glucose-dependent manner, improves glucose-stimulated insulin secretion and demonstrates effects on glycemic control in patients with T2D. We report the findings of a randomized, double-blind, placebo-controlled phase 3 clinical trial to evaluate the efficacy and safety of dorzagliatin in patients with T2D. Eligible drug-naïve patients with T2D (n = 463) were randomly assigned to the dorzagliatin or placebo group at a ratio of 2:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin from baseline to week 24. Safety was assessed throughout the trial. At week 24, the least-squares mean change in glycated hemoglobin from baseline (95% confidence interval) was -1.07% (-1.19%, -0.95%) in the dorzagliatin group and -0.50% (-0.68%, -0.32%) in the placebo group (estimated treatment difference, -0.57%; 95% confidence interval: -0.79%, -0.36%; P < 0.001). The incidence of adverse events was similar between the two groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin group. In summary, dorzagliatin improved glycemic control in drug-naïve patients with T2D and showed a good tolerability and safety profile.

5.
Health Serv Res ; 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522231

RESUMO

OBJECTIVE: To compare physician versus practice-level primary care continuity and their association with expenditure and acute care utilization among Medicare beneficiaries and evaluate if continuity of outpatient primary care at either/both physician or/and practice level could be useful quality measures. DATA SOURCE: Medicare Fee-For-Service claims data for community dwelling beneficiaries without End-Stage Renal Disease who were attributed to a national random sample of primary care practices billing Medicare (2011-2017). STUDY DESIGN: Retrospective secondary data analysis at per Medicare beneficiary per year level. We used multivariable linear regression with practice-level fixed effects to estimate continuity of care score at physician vs. practice level and their associations with outcomes. DATA COLLECTION/EXTRACTION METHOD: We calculated clinician and practice level Bice-Boxerman continuity of care index scores, ranging from 0 to 1, using primary care outpatient claims. Medicare expenditures, hospital admissions, emergency department visits, and readmissions were obtained from the Medicare Beneficiary Summary File: Cost and Utilization Segment. Ambulatory care sensitive conditions (ACSC) were defined using diagnosis codes on inpatient claims. PRINCIPAL FINDINGS: We studied 2,359,400 beneficiaries who sought care from 13,926 physicians. Every 0.1 increase in physician continuity score was associated with a $151 reduction in expenditures per beneficiary per year (P<0.01), and every 0.1 increase in practice continuity score was associated with $282 decrease (P<0.01) per beneficiary per year. Both physician- and practice-level continuity were associated with lower Medicare expenditures among small, medium, and large practices. Both physician- and practice-level continuity were associated with lower probabilities of hospitalization, emergency department visit, admissions for ACSC, and readmission. CONCLUSIONS: Primary care continuity of care could serve as a potent value-based care quality metric. Physician-level continuity is a unique value center that cannot be supplanted by practice level continuity.

6.
RSC Adv ; 12(22): 13756-13764, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35530380

RESUMO

Novel star-like molecules containing P, N and Si with dual functions of flame retardance and curing promotion (abridged as HCCP-KH540) were successfully synthesized through the nucleophilic substitution reaction of hexachlorocyclotriphosphazene (HCCP) and 3-aminopropyltrimethoxysilane (KH540). HCCP-KH540 was incorporated with the matrix of epoxy resin (EP) to form a flame retardant composite abridged as E-HK. The activation energy of the curing reaction of the E-HK composite was reduced but the curing reaction rate was accelerated by HCCP-KH540. The E-HK composite with 30 phr content of HCCP-KH540 exhibited excellent flame retardancy with limiting oxygen index of 29.6% and V-1 rating in the vertical burning test as well as excellent thermal stability with a char yield of 23.77% at 700 °C, compared with only 8.64% for pure EP.

7.
Soft Matter ; 18(17): 3328-3334, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35385566

RESUMO

In this work, we investigate the three-dimensional lattice deformation of blue phase (BP) liquid crystals under electrostriction. Using the in situ measurement of light diffraction signals from a twinned crystal, we propose a method to experimentally determine the lattice constants of BPs under an electric field; the overlap angle in the diffraction pattern of BP twinning domains gives the ratio of lattice constants in the lateral direction of the field, which can be analyzed together with the Bragg reflection peak wavelength along the field direction to yield three-dimensional lattice constants. The obtained values are confirmed to show good agreement with the diffraction data measured from a converging monochromatic light. Furthermore, by applying the method to BPs in a thin cell and specifying the transitions of azimuthal orientation, three-dimensional lattice deformation of BP I crystals and evolution of the azimuthal orientation are clarified under the electrostriction. Results reveal that the BPs confined to thin films undergo discrete elongation along the field direction and the BP I crystal undergoes larger lattice deformation in the field-perpendicular directions than that along the field. Our work allows a relatively easy determination of three-dimensional lattice constants of deformed BP crystals under an electric field, and the obtained results provide important insights into the understanding of the electrostriction behaviour of BPs towards improvement of the electro-optical performance of BP devices in practical applications.

8.
J Mater Chem B ; 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35470824

RESUMO

Transformable peptides (TPs) are biomedical materials with unique structures and diverse functionalities that have drawn great interest in materials science and nanomedicine. Here, we design a series of TPs with five self-assembling sequences conjugated with the hydrophobic unit bis(pyrene) and the targeting sequence RGD, and study the transformable features induced by ligand (RGD)-receptor (integrin or Ca2+) interactions. TPs are able to self-assemble into nanoparticles or nanosheets and then transform into nano-aggregates or nanofibers induced by RGD-Ca2+ interactions in solution. When TPs are incubated with breast cancer cells expressing integrin receptors on the cell membrane, it is found that they display different cell distributions, including adhesion on the cell membrane, location in the lysosome, or escape from the lysosome to cytoplasm. This study reveals that the self-assembling sequence affects the dynamic self-assembly nanostructures of TPs and the resultant biodistribution in cells.

9.
Ecotoxicol Environ Saf ; 236: 113475, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35364508

RESUMO

Most aquatic ecosystems are at risk of being polluted by new environmental pollutant nanoparticles. As the main food source of zooplankton, the biomass of algae always fluctuates. Cladocerans, an important part of zooplankton, are usually be simultaneously exposed to different abundance of algae and nanoparticles in aquatic environment. To evaluate the combined effects of food abundance and ZnO nanoparticles concentration on the development and early reproductive performance of cladocerans, we exposed Daphnia magna, a common and representative model organism in cladocerans, to the combinations of different abundances of Chlorella pyrenoidosa and different concentrations of ZnO nanoparticles, recorded the key life-history traits, and used multiple models to fit the data. Results showed that high level of ZnO nanoparticles and low abundance Chlorella had an interactively negative effect on the life history of D. magna. When D. magna was exposed to ZnO nanoparticles, some life history traits, such as survival time, body length at maturation, and offspring per female, increased exponentially with the increase of food abundance, and then reached a theoretical maximum value, whereas some other life history traits, such as time to maturation and time to first brood, showed an opposite trend. However, higher Chlorella abundance reduced the negative effect of ZnO nanoparticles on D. magna, but the negative effect could not be eliminated with the increase of food abundance. Below Chlorella 0.30 mg C L-1, food plays a decisive role, while at or above this threshold, ZnO nanoparticles play a decisive role. Therefore, the effect of different ZnO nanoparticles concentrations can be fully reflected only when food is sufficient, and the negative effects of food shortages may mask the toxic effects of ZnO nanoparticles on D. magna. The findings indicated that the effects of food abundance should be considered in evaluating the realistic impact of pollutants on zooplankton.


Assuntos
Chlorella , Nanopartículas , Poluentes Químicos da Água , Óxido de Zinco , Animais , Daphnia , Ecossistema , Feminino , Nanopartículas/toxicidade , Reprodução , Poluentes Químicos da Água/toxicidade , Óxido de Zinco/toxicidade , Zooplâncton
10.
Huan Jing Ke Xue ; 43(4): 2055-2061, 2022 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-35393829

RESUMO

The anaerobic environment of sewers is the main cause of the production of toxic and harmful gases such as hydrogen sulfide and methane. The installation of septic-tanks between the drainage standpipes and municipal sewage pipes has aggravated the current situation of poor ventilation in sewage pipes. A system of enhanced ventilation has been formed. By connecting the drainage standpipes and sewage pipes, the system of enhanced ventilation can ameliorate the ventilation of sewage pipes and improve the gas-phase space environment. The experimental and computational fluid dynamics (CFD) simulation methods were established to explore the law of oxygen gas-liquid mass transfer under the different sewage flow rates or wind speeds. This study aimed to seek a method to enhance the oxygen mass transfer, suppress the anaerobic environment, and achieve the purpose of long-term control of harmful gases. The results showed that increasing the gas-liquid flow rates can accelerate the oxygen mass transfer, and the volumetric mass transfer coefficient increased by 3.5×10-4 min-1 for every increase of 0.1 m·s-1. However, the faster sewage reduced hydraulic retention time. The mass transfer time of oxygen was also shortened, and the promotion effect was not as good as that by enhancing the gas velocity in the pipelines. At the same time, when the average gas velocity increased by 0.1 m·s-1, the lengths of pipes where dissolved oxygen could effectively inhibit H2S increased by 25 m.


Assuntos
Sulfeto de Hidrogênio , Esgotos , Gases , Metano , Oxigênio
11.
Orthop Surg ; 14(5): 851-859, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35434904

RESUMO

OBJECTIVE: To evaluate whether core decompression could prevent progression of asymptomatic type C osteonecrosis of the femoral head (ONFH) according to the Japanese Investigation Committee (JIC) classification. METHODS: This retrospective cohort study included 124 hips (117 patients) with asymptomatic type C ONFH. Seventy-one hips (67 patients) received core decompression (core decompression group) and 53 hips (50 patients) received no surgical treatment (control group). Clinical and radiological follow-up was conducted at 6 and 12 months, then annually until 5 years. Clinical outcomes were evaluated in terms of the Oxford hip score and UCLA Activity Level rating. Radiological outcomes were evaluated using X-ray and magnetic resonance imaging. Survival analysis was performed based on collapse of the femoral head as the first endpoint and total hip arthroplasty (THA) as the second endpoint. RESULTS: There were no significant differences in clinical outcomes between the core decompression group and the control group within 2 years after surgery. Patients in the core decompression group had significantly better Oxford hip score and UCLA Activity Level from year 3 to the end of follow-up (P < 0.05). In year 5, the absolute difference in Oxford hip score (5.3 points) exceeded the reported minimal clinically important difference (MCID, 5.2 points). In years 3-5, the absolute difference in UCLA Activity Level rating (0.95 points, 0.95 points, and 0.99 points, respectively) exceeded the reported MCID (0.92 points). By 5-year follow-up, significantly fewer patients in the core decompression group had experienced femoral head collapse (40.8% vs 62.3%, P = 0.011) or received THA (26.8% vs 45.3%, p = 0.022). CONCLUSIONS: Core decompression can prevent progression of asymptomatic type C ONFH according to the JIC classification, leading to better medium-term hip function and activity levels than no surgical treatment. Core decompression is recommended for early intervention against asymptomatic type C ONFH.


Assuntos
Necrose da Cabeça do Fêmur , Cabeça do Fêmur , Descompressão Cirúrgica/métodos , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/cirurgia , Necrose da Cabeça do Fêmur/prevenção & controle , Necrose da Cabeça do Fêmur/cirurgia , Seguimentos , Humanos , Japão , Estudos Retrospectivos , Resultado do Tratamento
12.
Sci Rep ; 12(1): 4677, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35304503

RESUMO

The aim of this study was to explore the overlapping key genes, pathway networks and transcription factors (TFs) related to the pathogenesis of rheumatoid arthritis (RA) and atherosclerosis. The gene expression profiles of RA and atherosclerosis were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between RA and atherosclerosis were identified. The biological roles of common DEGs were explored through enrichment analysis. Hub genes were identified using protein-protein interaction networks. TFs were predicted using Transcriptional Regulatory Relationships Unraveled by Sentence Based Text Mining (TRRUST) database. The hub genes and TFs were validated with other datasets. The networks between TFs and hub genes were constructed by CytoScape software. A total of 131 DEGs (all upregulated) were identified. Functional enrichment analyses indicated that DEGs were mostly enriched in leukocyte migration, neutrophil activation, and phagocytosis. CytoScape demonstrated 12 hub genes and one gene cluster module. Four of the 12 hub genes (CSF1R, CD86, PTPRC, and CD53) were validated by other datasets. TRRUST predicted two TFs, including Spi-1 proto-oncogene (SPI1) and RUNX family transcription factor 1(RUNX1). The expression of RUNX1 was validated with another dataset. Our study explored the common pathogenesis of RA and atherosclerosis. These results may guide future experimental research and clinical transformation.


Assuntos
Artrite Reumatoide , Aterosclerose , Artrite Reumatoide/complicações , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Aterosclerose/complicações , Aterosclerose/genética , Biologia Computacional/métodos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Mapas de Interação de Proteínas/genética
13.
ACS Appl Mater Interfaces ; 14(13): 14842-14858, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35319184

RESUMO

Liquid crystalline elastomers (LCEs) have emerged as an important class of functional materials that are suitable for a wide range of applications, such as sensors, actuators, and soft robotics. The unique properties of LCEs originate from the combination between liquid crystal and elastomeric network. The control of macroscopic liquid crystalline orientation and network structure is crucial to realizing the useful functionalities of LCEs. A variety of chemistries have been developed to fabricate LCEs, including hydrosilylation, free radical polymerization of acrylate, and polyaddition of epoxy and carboxylic acid. Over the past few years, the use of click chemistry has become a more robust and energy-efficient way to construct LCEs with desired structures. This article provides an overview of emerging LCEs based on click chemistries, including aza-Michael addition between amine and acrylate, radical-mediated thiol-ene and thiol-yne reactions, base-catalyzed thiol-acrylate and thiol-epoxy reactions, copper-catalyzed azide-alkyne cycloaddition, and Diels-Alder cycloaddition. The similarities and differences of these reactions are discussed, with particular attention focused on the strengths and limitations of each reaction for the preparation of LCEs with controlled structures and orientations. The compatibility of these reactions with the traditional and emerging processing techniques, such as surface alignment and additive manufacturing, are surveyed. Finally, the challenges and opportunities of using click chemistry for the design of LCEs with advanced functionalities and applications are discussed.

14.
Phytochem Anal ; 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35238089

RESUMO

INTRODUCTION: Alkaloids and glycosides are the active ingredients of the herb Dendrobium nobile, which is used in traditional Chinese medicine. The pharmacological effects of alkaloids include neuroprotective effects and regulatory effects on glucose and lipid metabolism, while glycosides improve the immune system. The pharmacological activities of the above chemical components are significantly different. In practice, the stems of 3-year-old D. nobile are usually used as the main source of Dendrobii Caulis. However, it has not been reported whether this harvesting time is appropriate. OBJECTIVE: The aim of this study was to compare the chemical characteristics of D. nobile in different growth years (1-3 years). METHODS: In this study, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) was employed to analyze the constituents of D. nobile. The relative abundance of each constituent was analyzed with multivariate statistical analyses to screen the characteristic constituents that contributed to the characterization and classification of D. nobile. Dendrobine, a component of D. nobile that is used for quality control according to the Chinese Pharmacopoeia, was assayed by gas chromatography. RESULTS: As a result, 34 characteristic constituents (VIP > 2) were identified or tentatively identified as alkaloids and glycosides based on MS/MS data. Moreover, the content of alkaloids decreased over time, whereas the content of glycosides showed the opposite trend. The absolute quantification of dendrobine was consistent with the metabolomics results. CONCLUSION: Our findings provide valuable information to optimize the harvest period and a reference for the clinical application of D. nobile.

15.
Front Oncol ; 12: 795159, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242705

RESUMO

Due to the emergence of traditional drug resistance in tumor treatment, the anti-cancer therapies are facing multiple challenges. Immunotherapy, as a new and universal treatment, has been gradually concerned. The macrophages, as an important part of the immune system, play an important role in it. Many studies have shown that immune state is essential in cancer progression and prognosis, rebuilding the architecture and functional orientation of the tumor region. Most tumors are complex ecosystems that change temporally and spatially under the pressure of proliferation, apoptosis, and extension of every cell in the microenvironment. Here, we review how macrophages states can be dynamically altered in different metabolic states and we also focus on the formation of immune exhaustion. Finally, we look forward to the explorations of clinical treatment for immune metabolism process.

16.
Ecotoxicol Environ Saf ; 233: 113352, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35240501

RESUMO

The decline in freshwater calcium has become a new environmental stressor to Daphnia with high calcium demand, however, the population dynamics and sexual reproduction of Daphnia under low calcium stress are still lack of deep understanding. To evaluate the impact of declined calcium on Daphnia from population level, we respectively exposed two clones of Daphnia pulex (CH and SH) to different calcium concentrations (0.5, 1.0, 1.5, 5.0, 10.0, 25.0 mg L-1) for 30 days and recorded the population indicators. Results showed that total biomass, average dry weight per individual, total number of ephippia, total number of resting eggs of Daphnia pulex CH clone at 1.0 mg L-1 calcium decreased by 75.5%, 34.0%, 83.6%, and 77.6% compared with those at 25 mg L-1 calcium, while SH clone at 1.0 mg L-1 calcium decreased by 64.6%, 26.1%, 94.5%, and 82.2%, respectively. Importantly, Ca content in dry Daphnia pulex population of CH clone at 1.0 and 1.5 mg L-1 calcium decreased by 32.7% and 6.7% compared to those at 25 mg L-1 calcium, and SH clone at 1.0 mg L-1 and 1.5 mg L-1 calcium also decreased by 30.9% and 10.5%, respectively. Furthermore, low calcium significantly decreased the perimeter and surface area of ephippia. Interestingly, observation by scanning electron microscope found that low calcium changed the surface of ephippia. The negative impact of calcium decline on Daphnia population and sexual reproduction will inevitably endanger the persistence of species and genes at meta population level.


Assuntos
Cálcio , Daphnia , Animais , Daphnia/genética , Água Doce , Dinâmica Populacional , Reprodução
17.
J Food Biochem ; : e14105, 2022 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-35128669

RESUMO

Pomegranate peel (PP) is a by-product in the processing of pomegranate products, which is usually discarded as a waste. However, a large number of researches have shown that pomegranate peel extract (PPE) is rich in a variety of phenolic substances, among which ellagic acid (EA), as one of the main active components, has significant biological activities, such as anti-oxidation, anti-tumor, anti-inflammatory, neuroprotection, anti-viral, and anti-bacterial. We analyzed the mechanism of EA's biological activity, and discussed its application in the food industry, for instance, food preservation, food additives, and functional foods. Combined with the research status of PPE, we discussed the limitations and development potential of PPE, in order to provide theoretical reference and scientific basis for the development and utilization of pomegranate by-products. PRACTICAL APPLICATIONS: Pomegranate peel (PP), the inedible part of the fruit, is usually treated as waste. In recent years, researchers have been committed to exploring various bioactive ingredients in PP and exploring its potential benefits to human health, which has far-reaching significance. In this paper, the chemical constituents of polyphenols in PP were reviewed, mainly focusing on the biological activity and mechanism of ellagic acid (EA). We reviewed the applications and invention patents of pomegranate peel extract (PPE) in food field, including food preservation, food additive, and functional foods, providing reference for the recycling and reuse of PP.

18.
BMC Immunol ; 23(1): 6, 2022 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-35152883

RESUMO

BACKGROUND: Immune response is prevalently related with major depressive disorder (MDD) pathophysiology. However, the study on the relationship between immune-related genes (IRGs) and immune infiltrates of MDD remains scarce. METHODS: We extracted expression data of 148 MDD patients from 2 cohorts, and systematically characterized differentially expressed IRGs by using limma package in R software. Then, the LASSO and multivariate logistic regression analysis was used to identify the most powerful IRGs. Next, we analyzed the relationship between IRGs and immune infiltrates of MDD. Finally, GSE76826 was used to to verificate of IRGs as a diagnostic markers in MDD. RESULTS: 203 different IRGs s in MDD has been identified (P < 0.05). GSEA revealed that the different IRGs was more likely to be enriched in immune-specific pathways. Then, a 9 IRGs was successfully established to predict MDD based on LASSO. Next, 4 IRGs was obtained by multivariate logistic regression analysis, and AUC for CD1C, SPP1, CD3D, CAMKK2, and IRGs model was 0.733, 0.767, 0.816, 0.800, and 0.861, suggesting that they have a good diagnostic performance. Furthermore, the proportion of T cells CD8, T cells γδ, macrophages M0, and NK cells resting in MDD group was lower than that in the healthy controls, suggesting that the immune system in MDD group is impaired. Simultaneously, CD3D was validated a reliable marker in MDD, and was positively correlated with T cells CD8. GSEA revealed high expression CD3D was more likely to be enriched in immune-specific pathways, and low expression CD3D was more likely to be enriched in glucose metabolism metabolism-specific pathways. CONCLUSIONS: We applied bioinformatics approaches to suggest that a 4 IRGs could serve as diagnostic markers to provide a novel direction to explore the pathogenesis of MDD.


Assuntos
Transtorno Depressivo Maior , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/genética , Biologia Computacional , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/genética , Humanos , Prognóstico
19.
Acta Biomater ; 143: 372-380, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35219868

RESUMO

Stimuli-responsive nanoplatforms for efficient delivery of drugs in an on-demand manner show promising potential for killing cancer cells with high accuracy and minimal invasiveness. Herein, taking advantage of the good tissue-penetrating depth of sonodynamic therapy (SDT), reactive oxygen species (ROS)-responsive nanoscale coordination polymers (NCPs) were designed through self-assembly of porphyrins (PP) and platinum, which contained ROS-cleavable thioketal (TK) linkers to enhance the release of doxorubicin (Dox) during SDT. Upon exposure to the ultrasound (US), the Dox-loaded NCPs (PTK@PEG/Dox) could generate high amounts of cytotoxic ROS and heat, which not only induced the apoptosis of MCF-7 cells but also facilitated the efficient release of Dox due to the decomposition of the ROS-sensitive TK linkers, achieving the synergistic therapy of US-induced therapy and chemotherapy. After being modified with Arg-Gly-Asp (RGD) peptide, RGD/PTK@PEG exhibited a good targeting ability to cancer cells. Importantly, using the multicellular tumor spheroids (MCTS) derived from MCF-7 cells as a model, the RGD/PTK@PEG/Dox exhibited an efficient and controlled release behavior of Dox under the US irradiation, accompanying a tremendous anti-cancer effect for inducing apoptosis in the solid tumor tissues. This work provided a potential strategy to design controllable and stimuli-responsive nanoplatforms for synergistic/enhanced US-induced cancer therapy. STATEMENT OF SIGNIFICANCE: Stimulus-responsive nanoplatforms can deliver drugs efficiently in an on-demand manner, showing the potential to kill cancer cells with high accuracy and minimal invasiveness. Taking advantage of the good penetration ability of ultrasound (US), nanoscale coordination polymers (NCP) composed of porphyrin (PP), thioketal (TK) linkers, and platinum(II) were prepared via a coordination-driven self-assembly procedure. After doxorubicin (Dox) was loaded on the NCP (PTK@PEG/Dox), the nanoplatform responded to reactive oxygen species (ROS) under the stimulation of US, and induced the on-demand release of Dox, thereby achieving the combined therapeutic effect of sonodynamic therapy (SDT) and chemotherapy for cancer. This work provides a potential strategy for the development of controllable and stimuli-responsive nanoplatforms for enhanced ultrasound-induced cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Porfirinas , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Platina , Polímeros/química , Espécies Reativas de Oxigênio
20.
Materials (Basel) ; 15(3)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35160863

RESUMO

Janus wettability plays an important role in certain special occasions. In this study, field emission scanning electron microscopy (FESEM) was used to observe the surface microstructure of banana leaves, the static wettability of the banana leaf surface was tested, and the dynamic response of water droplets falling at different heights and hitting on the adaxial and abaxial sides was studied. The study found that the nanopillars on the adaxial and abaxial sides of the banana leaf were different in shape. The nanopillars on the adaxial side were cone-shaped with large gaps, showing hydrophilicity (Wenzel state), and the heads of the nanopillars on the abaxial side were smooth and spherical with small gaps, showing weak hydrophobicity (Cassie-Baxter state). Banana leaves show Janus wettability, and the banana leaf surface has high adhesion properties. During the dynamic impact test, the adaxial and abaxial sides of the banana leaves showed different dynamic responses, and the wettability of the adaxial side of the banana leaves was always stronger than the abaxial side. Based on the structural parameters of nanopillars on the surface of the banana leaf and the classical wetting theory model, an ideal geometric model around a single nanopillar on both sides of the banana leaf was established. The results show that the established model has high accuracy and can reflect the experimental results effectively. When the apparent contact angle was 76.17°, and the intrinsic contact angle was 81.17° on the adaxial side of the banana leaf, steady hydrophilicity was shown. The abaxial side was similar. The underlying mechanism of Janus wettability on the banana leaf surface was elucidated. This study provides an important reference for the preparation of Janus wettability bionic surfaces and the efficient and high-quality management of banana orchards.

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