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1.
Small ; : e2206228, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599642

RESUMO

The precise regulation of interactions of specific immunological components is crucial for controllable immunomodulation, yet it remains a great challenge. With the assistance of advanced computer design, programmable nucleic acid nanotechnology enables the customization of synthetic nucleic acid nanodevices with unprecedented geometrical and functional precision, which have shown promising potential for precise immunoengineering. Notably, the inherently immunologic functions of nucleic acids endow these nucleic acid-based assemblies with innate advantages in immunomodulatory engagement. In this review, the roles of nucleic acids in innate immunity are discussed, focusing on the definition, immunologic modularity, and enhanced bioavailability of structural nucleic acid nanodevices. In light of this, molecular programming and precise organization of functional modules with nucleic acid nanodevices for immunomodulation are emphatically reviewed. At last, the present challenges and future perspectives of nucleic acid nanodevices for immunomodulation are discussed.

2.
Small ; : e2205941, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36587967

RESUMO

Drug-resistant bacterial infection impairs tissue regeneration and is a challenging clinical problem. Metal-organic frameworks (MOFs)-based photodynamic therapy (PDT) opens up a new era for antibiotic-free infection treatment. However, the MOF-based PDT normally encounters limited photon absorbance under visible light and notorious recombination of photogenerated holes and electrons, which significantly impede their applications. Herein, a MOFs-based nanosystem (AgNPs@MOFs) with enhanced visible light response and charge carrier separation is developed by modifying MOFs with silver nanoparticles (AgNPs) to improve PDT efficiency. The AgNPs@MOFs with enhanced photodynamic performance under visible light irradiation mainly disrupt bacteria translation process and the metabolism of purine and pyrimidine. In addition, the introduction of AgNPs endows nanosystems with chemotherapy ability, which causes destructive effect on bacterial cell membrane, including membrane ATPase protein and fatty acids. AgNPs@MOFs show excellent synergistic drug-resistant bacterial killing efficiency through multiple mechanisms, which further restrain bacterial resistance. In addition, biocompatible AgNPs@MOFs pose potential tissue regeneration ability in both Methicillin-resistant Staphylococcus aureus (MRSA)-related soft and hard tissue infection. Overall, this study provides a promising perspective in the exploration of AgNPs@MOFs as nano antibacterial medicine against drug-resistant bacteria for infected tissue regeneration in the future.

3.
Arch Dermatol Res ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36652006

RESUMO

Publicly available provider-level Medicare Part B data sets have been increasingly utilized for health services research in dermatology. Despite offering detailed insights, an important limitation of these data sets is suppression of services performed for < 11 Medicare beneficiaries at the level of each provider. This longitudinal review assesses the magnitude of this limitation by comparing service counts in provider-level Medicare data sets to those in aggregate data sets, ultimately identifying a concordance rate of 94.3% for dermatology services. However, facility-based visits (52.5%), inpatient evaluation and management visits (59.7%), phototherapy (62.9%), incision and drainage (61.1%), and nail procedures (38.0%) were less well-represented in the provider-level data sets. Provider-level data sets are most suitable for assessing dermatology services in aggregate and among specific high-volume procedure groups but alternative data sets should be considered when investigating inpatient services, facility-based services (more common in certain states), or rarely performed procedures.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36689577

RESUMO

Natural biopolymers can be controllably in situ synthesized in organisms and play important roles in biological activities. Inspired by this, the manipulation of in situ biosynthesis of functional polymers in vivo will be an important way to obtain materials for meeting biological requirements. Herein, in situ biosynthesis of functional conjugated polymer at the tumor site was achieved via the utilization of specific tumor microenvironment (TME) characteristics for the first time. Specially, a water-soluble aniline dimer derivative (N-(3-sulfopropyl) p-aminodiphenylamine, SPA) was artfully in situ polymerized into polySPA (PSPA) nanoparticles at the tumor site, which was activated via the catalysis of hydrogen peroxide (H2O2) overexpressed in TME to produce hydroxyl radical (•OH) by coinjected horseradish peroxidase (HRP). Benefiting from outstanding near-infrared (NIR)-II absorption of PSPA, the in situ polymerization process can be validly monitored by photoacoustic (PA) signal at the NIR-II region. Meanwhile, in situ polymerization would induce the size of polymeric materials from small to large, improving the distribution and retention of PSPA at the tumor site. On the combination of NIR-II absorption of PSPA and the size variation induced by polymerization, such polymerization can be applied for tumor-specific NIR-II light mediated PA image and photothermal inhibition of tumors, enhancing the precision and efficacy of tumor phototheranostics. Therefore, the present work opens the way to manipulate TME-activated in situ biosynthesis of functional conjugated polymer at the tumor site for overcoming formidable challenges in tumor theranostics.

5.
Dev Comp Immunol ; 141: 104631, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36608898

RESUMO

Teleosts rely on innate immunity to recognize and defense against pathogenic microorganisms. RIG-I-like receptor (RLR) family is the major pattern recognition receptor (PRR) to detect RNA viruses. After recognition of viral RNA components, these cytosolic sensors activate downstream signaling cascades to induce the expression of type I interferons (IFNs) and other cytokines firing antiviral responses. Meanwhile, numerous molecules take part in the complex regulation of RLR signals by various methods, such as post-translational modification (PTM), to produce an immune response that is appropriately balanced. In this review, we summarize our recent understanding of PTMs and other regulatory proteins in modulating RLR signaling pathway, which is helpful for systematically studying the regulatory mechanism of antiviral innate immunity of teleost fish.

6.
Environ Int ; 171: 107741, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36628860

RESUMO

BACKGROUND: It remains unclear whether type 2 diabetes and the complication of arthritis are causally related to the PM2.5 pollutant. Therefore, we aimed to investigate the associations of long-term PM2.5 exposure with type 2 diabetes and with arthritis in type 2 diabetes patients. MATERIALS AND METHODS: This study used data from the China Health and Retirement Longitudinal Survey (CHARLS) implemented during 2011-2018. The associations were analyzed by Cox proportional hazards regression models, and the population-attributable fraction (PAF) was calculated to assess the burden of type 2 diabetes and arthritis-attributable to PM2.5. RESULTS: A total of 21,075 participants were finally included, with 19,121 analyzed for PM2.5 and type 2 diabetes risk and 12,427 analyzed for PM2.5 and arthritis risk, of which 1,382 with newly-diagnosed type 2 diabetes and 1,328 with arthritis during the follow-up. Overall, each 10 µg/m3 increment in PM2.5 concentration was significantly associated with an increase in the risk of type 2 diabetes (HR = 1.26, 95 %CI1.22 to 1.31), and the PAF of type 2 diabetes attributable to PM2.5 was 13.54 %. In type 2 diabetes patients, each 10 µg/m3 increment in PM2.5 exposure was associated with an increase in arthritis (HR = 1.42, 95 %CI: 1.28 to 1.57), and the association was significantly greater than that (H = 1.23, 95 %CI: 1.19 to 1.28) in adults without type 2 diabetes. The PAFs of arthritis-attributable to PM2.5 in participants with and without type 2 diabetes were 18.54 % and 10.69 %, respectively. CONCLUSION: Long-term exposure to PM2.5 may increase the risk of type 2 diabetes and make type 2 diabetes patients susceptible to arthritis.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Diabetes Mellitus Tipo 2 , Adulto , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Exposição Ambiental/análise , China/epidemiologia
7.
Int J Mol Sci ; 24(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36675303

RESUMO

Stroke, one of the leading causes of disability and death worldwide, is a severe neurological disease that threatens human life. Protopanaxatriol (PPT), panaxatriol-type saponin aglycone, is a rare saponin that exists in Panax ginseng and Panax Noto-ginseng. In this study, we established an oxygen-glucose deprivation (OGD)-PC12 cell model and middle cerebral artery occlusion/reperfusion (MCAO/R) model to evaluate the neuroprotective effects of PPT in vitro and in vivo. In addition, metabolomics analysis was performed on rat plasma and brain tissue samples to find relevant biomarkers and metabolic pathways. The results showed that PPT could significantly regulate the levels of LDH, MDA, SOD, TNF-α and IL-6 factors in OGD-PC12 cells in vitro. PPT can reduce the neurological deficit score and infarct volume of brain tissue in rats, restore the integrity of the blood-brain barrier, reduce pathological damage, and regulate TNF-α, IL-1ß, IL-6, MDA, and SOD factors. In addition, the results of metabolomics found that PPT can regulate 19 biomarkers involving five metabolic pathways, including amino acid metabolism, arachidonic acid metabolism, sphingolipid metabolism, and glycerophospholipid metabolism. Thus, it could be inferred that PPT might serve as a novel natural agent for MCAO/R treatment.


Assuntos
Isquemia Encefálica , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Saponinas , Ratos , Humanos , Animais , Isquemia Encefálica/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fator de Necrose Tumoral alfa , Interleucina-6 , Infarto da Artéria Cerebral Média/patologia , Glucose , Traumatismo por Reperfusão/metabolismo , Saponinas/farmacologia , Saponinas/uso terapêutico , Superóxido Dismutase
8.
Materials (Basel) ; 16(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36676263

RESUMO

Graphene and graphene-based materials gifted with high electrical conductivity are potential alternatives in various related fields. However, the electrical conductivity of the macro-graphene materials is much lower than their metal counterparts. Herein, we improved the electrical conductivity of reduced graphene oxide (rGO) based graphene assembled films (GAFs) by applying a series of compressive stress and systematically investigated the relationship between the compressive stress and the electrical conductivity. The result indicates that with increasing applied compressive stress, the sheet resistance increased as well, while the thickness decreased. Under the combined effect of these two competing factors, the number of charge carriers per unit volume increased dramatically, and the conductivity of compressed GAFs (c-GAFs) showed an initial increasing trend as we applied higher pressure and reached a maximum of 5.37 × 105 S/m at the optimal stress of 450 MPa with a subsequent decrease with stress at 550 MPa. Furthermore, the c-GAFs were fabricated into strain sensors and showed better stability and sensitivity compared with GAF-based sensors. This work revealed the mechanism of the tunable conductivity and presented a facile and universal method for improving the electrical conductivity of macro-graphene materials in a controllable manner and proved the potential applications of such materials in flexible electronics like antennas, sensors, and wearable devices.

10.
J Hazard Mater ; 445: 130481, 2023 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-36493653

RESUMO

Highly efficient charge transfer is a critical factor to modulate the photocatalytic activity. However, the conscious modulation of charge transfer efficiency is still a great challenge. Herein, a novel interfacial Mo-N bond and appropriate oxygen vacancies (OVs) modulated S-scheme MoO3-x/S-CN heterojunction was rationally fabricated for efficient photocatalytic disinfection. The results of characterizations and density functional theory (DFT) calculations suggested that the enhanced charge transfer dynamics is ascribed to the optimizing oxygen vacancies density and forming interfacial Mo-N bond. It can improve charge transfer efficiency from 36.4% (MoO3-x) to 52.5% (MoO3-x/S-CN) and produce more reactive oxygen species (ROS), achieving entirely inactivate of 7.60-log E. coli and S. aureus within 50 min and 75 min. Besides, MoO3-x/S-CN can well resist the disturbance from the coexisting substances, and can be applied in a wide pH range, and even authentic water bodies. Monitoring of bacterial antioxidant systems and membrane integrity revealed that bacterial inactivation begins with the oxidation of cell membrane and dies from leakage of intracellular substances and destruction of cell structure. This work provides an inspiration on consciously modulating S-scheme charge transfer efficiency by optimizing oxygen vacancies density and atomic-level interface control for promoting the photocatalytic antibacterial activity.


Assuntos
Desinfecção , Oxigênio , Escherichia coli , Staphylococcus aureus , Espécies Reativas de Oxigênio
11.
Dev Comp Immunol ; 140: 104614, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36502963

RESUMO

From mammals to fish, interferons (IFNs) play vital roles in the immune response. In this study, a newly identified type IV interferon (bcIFN-υ) from black carp (Mylopharyngodon piceus) has been cloned and characterized. The CDS of bcIFN-υ consists of 489 nucleotides, encoding 163 amino acids, with the first 20 amino acids predicted to be the signal peptide region. The immunoblot and immunofluorescence assays verified that bcIFN-υ was a secreted cytokine. qPCR analysis and reporter assay demonstrated that bcIFN-υ participated in innate immune defense and activated the transcription of fish ISRE promoter under spring viremia of carp virus (SVCV) stimulation. Additionally, compared with control group, EPC cells transfected with bcIFN-υ or incubated with the bcIFN-υ-containing conditioned media before SVCV infection showed greatly enhanced antiviral activity, and the transcription levels of MX1, PKR, ISG15 and Viperin genes were significantly increased. The subsequential co-immunoprecipitation assay identified the interaction between bcIFN-υ proteins. Collectively, our data conclude that bcIFN-υ is a kind of secretory protein with self-interaction and triggering the expression of downstream ISGs to enhance the antiviral activity of host cells.


Assuntos
Carpas , Doenças dos Peixes , Infecções por Reoviridae , Reoviridae , Infecções por Rhabdoviridae , Animais , Interferons/genética , Carpas/genética , Carpas/metabolismo , Reoviridae/fisiologia , Imunidade Inata/genética , Sequência de Aminoácidos , Clonagem Molecular , Antivirais , Proteínas de Peixes/metabolismo , Mamíferos/genética
12.
Talanta ; 254: 124138, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36463803

RESUMO

Lack of highly efficient, inexpensive, and easily available catalysts severely limits the practical applicability of electrochemically sensing assay towards 5-hydroxytryptamine (5-HT). Herein, four kinds of Fe-Co bimetallic Prussian blue analogues (FeCo-PBAs) with different molar ratios of Fe to Co were prepared using a simple coprecipitation method. Interestingly, Fe(III) in K3 [Fe(CN)6] can be reduced to Fe(II) by adding trisodium citrate dehydrate, which could offer a new clue to synthesize PBAs with Fe(II) core ions. With the optimizational FeCo-PBA synthesized at a 0.5/1 M ratio of Fe to Co as an electrocatalyst, the constructed sensor shows excellent comprehensive performance for the 5-HT assay with a high sensitivity of 0.856 µA µM-1 and an ultralow detection limit of 8.4 nM. Under the optimum conditions, linearity was obtained in the ranges of 0.1-10.0 µM and 10.0-200.0 µM and preferable recoveries ranged from 97.8% to 103.0% with relative standard deviation (RSD) < 4.0%. The integrated properties of FeCo-PBA can be comparable to previously reported electrocatalysts for the 5-HT assay including noble metal-based and expensive carbon (graphene and carbon nanotubes)-based electrocatalysts. The proposed sensor also exhibits outstanding selectivity, reproducibility, and practicality for real sample analyses. This work is the first report on the PBA-based sensor for the 5-HT assay, verifying the practicability of this high-performance sensor for the 5-HT assay.

13.
Brief Bioinform ; 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36472568

RESUMO

Accounting for cell type compositions has been very successful at analyzing high-throughput data from heterogeneous tissues. Differential gene expression analysis at cell type level is becoming increasingly popular, yielding biomarker discovery in a finer granularity within a particular cell type. Although several computational methods have been developed to identify cell type-specific differentially expressed genes (csDEG) from RNA-seq data, a systematic evaluation is yet to be performed. Here, we thoroughly benchmark six recently published methods: CellDMC, CARseq, TOAST, LRCDE, CeDAR and TCA, together with two classical methods, csSAM and DESeq2, for a comprehensive comparison. We aim to systematically evaluate the performance of popular csDEG detection methods and provide guidance to researchers. In simulation studies, we benchmark available methods under various scenarios of baseline expression levels, sample sizes, cell type compositions, expression level alterations, technical noises and biological dispersions. Real data analyses of three large datasets on inflammatory bowel disease, lung cancer and autism provide evaluation in both the gene level and the pathway level. We find that csDEG calling is strongly affected by effect size, baseline expression level and cell type compositions. Results imply that csDEG discovery is a challenging task itself, with room to improvements on handling low signal-to-noise ratio and low expression genes.

14.
ACS Nano ; 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36468939

RESUMO

Low power and high switching ratio are the development direction of the next generation of resistive random access memory (RRAM). Previous techniques could not increase the switching ratio while reducing the SET power. Here, we report a method to fabricate low-power and high-switching-ratio RRAM by adjusting the interstice radius (rg) between the van der Waals (vdW) layers of transitional-metal dichalcogenides (TMDs), which simultaneously increases the switching ratio and reduces the SET power. The SET voltage, SET power, switching ratio and endurance of the device are strongly correlated with rg. When the ratio of rg to the radius of the metal ions that form the conductive filaments (rg/rAg+) is near 1, the SET voltage and SET power vertically decrease while the switching ratio vertically rises with increasing rg/rAg+. For the fabricated Ag/[SnS2/poly(methyl methacrylate)]/Cu RRAM with an rg/rAg+ of 1.04, the SET voltage, SET power and switching ratio are 0.14 V, 10-10 W and 106, respectively. After 104 switching cycles and a 104 s retention time, the switching ratio of the device can still be stable above 106. Bending has no influence on the performance of the device when the bending radius is not <2 mm.

15.
Front Pharmacol ; 13: 1064470, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36561342

RESUMO

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with high mortality that urgently requires new treatments. ROCK1 plays an essential role in regulating growth and survival in AML cells. In this study, we evaluated GSK269962A, a selective ROCK1 inhibitor, in preclinical models of AML. Compared with solid tumors, GSK269962A selectively inhibited cell growth and clonogenicity of AML cells. Furthermore, GSK269962A arrested AML cells in the G2 phase and induced apoptosis by regulating multiple cell cycle- and apoptosis-associated proteins. Strikingly, GSK269962A could eliminate leukemia cells from bone marrow, liver, and spleen in an animal model of AML and significantly prolong mouse survival. Mechanistically, GSK269962A could inhibit the growth of AML by blocking ROCK1/c-Raf/ERK signaling pathway. Notably, a correlation was found between the expression levels of ROCK1 protein and the sensitivity of GSK269962A in AML. These data highlight the potential role of ROCK1 as an attractive target for treating AML, as well as the potential of GSK269962A for use in clinical trials of AML.

17.
Therap Adv Gastroenterol ; 15: 17562848221140662, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518883

RESUMO

Background: Various therapeutic strategies are available for the first-line treatment of patients with advanced hepatocellular carcinoma (aHCC). But which approach is the most cost-effective remains uncertain. Objectives: This study aims to evaluate the cost-effectiveness of first-line strategies in aHCC patients from the perspective of Chinese and US payers. Design: A network meta-analysis (NMA) and cost-effectiveness study. Data sources and methods: A NMA was conducted to collect all first-line strategies with aHCC from 1 October 1 2018 until 1 January 2022. The relevant randomized controlled trial literature in PubMed, Embase, and Cochrane Library for the last 3 years were searched. The abstracts of meetings of the American Society of Clinical Oncology, European Society of Medical Oncology, and American Association for Cancer Research were also reviewed. A Markov model that included three states was developed. One-way sensitivity and probabilistic sensitivity analysis were performed to investigate the uncertainty of the economic evaluation. Scenario analysis was conducted to explore the economic benefits of treatment strategies in low-income populations. Results: Base-case analysis in China included 1712 patients showed that atezolizumab combined with bevacizumab, sintilimab combined with bevacizumab, lenvatinib (LEVA), and sorafenib (SORA) added 0.46, 1.25, 0.77, and -1.08 quality-adjusted life-years (QALYs), respectively, compared with donafenib, resulting in an incremental cost-effective ratio of $85607.88, $12109.27, and $1651.47 per QALY at a willingness-to-pay (WTP) of $11101.70/QALY. In the United States, only the incremental cost-effectiveness ratios (ICERs) of SORA was higher that were lower than the WTP threshold ($69375/QALY), and LEVA was the most cost-effective strategy with the ICERs were 25022.13/QALY. Conclusion: The NMA and cost-effectiveness analysis revealed that LEVA is the favorite choice in the first-line treatment of Chinese aHCC patients and US payers' perspective when the WTP was $11101.70/QALY in China and $69375.0/QALY in the United States. Registration: This study has been registered on the PROSPERO database with the registration number CRD42021286575.

18.
Sci Bull (Beijing) ; 67(14): 1467-1476, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-36546190

RESUMO

We demonstrated an efficient solar photovoltaic-powered electrochemical CO2 reduction device with a high-pressure CO2-captured liquid feed. In an "air-to-barrel" picture, this device holds promise to avoid both high-temperature gaseous CO2 regeneration and high energy-cost gas product separation steps, while these steps are necessary for devices with a gaseous CO2 feed. To date, solar fuel production with a CO2-saturated liquid feed suffers from high over-potential to suppress the hydrogen evolution reaction and consequently, low solar-to-chemical (STC) energy conversion efficiency. Here, we presented a distinct high-pressure operando strategy, i.e., we took extra advantage of the high pressure in catalyst synthesis besides in the period of the CO2 reduction reaction (CO2RR). The power of this strategy was demonstrated by a proof-of-concept device in which a representative copper catalyst was first synthesized in operando in a high-pressure (50 bar) CO2-saturated KHCO3 solution, and then this high-pressure CO2-captured liquid was converted to solar fuel using the operando synthesized Cu catalyst. This Cu catalyst achieved 95% CO2RR selectivity at the recorded low potential of -0.3 V vs. RHE enabled by the combination of operando facet engineering and oxide derivation. Furthermore, this device achieved a record-high STC efficiency of 21.6% under outdoor illumination, superior to other CO2-saturated liquid-fed devices, and compared favorably to gaseous CO2-fed devices.

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