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1.
Skin Res Technol ; 30(3): e13641, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38426414

RESUMO

BACKGROUND: Frailty is associated with a variety of diseases, but the relationship between frailty and psoriasis remains unclear. METHODS: First, we conducted a two-sample Mendelian randomization based on genome-wide association studies (GWAS) to investigate genetic causality between frailty index and common diseases in dermatology. Inverse variance weighted was used to estimate causality. Second, expression quantitative trait locus (eQTLs) analysis was conducted to identify the genes affected by Single nucleotide polymorphisms (SNPs). Third, we performed function and pathway enrichment, transcriptome-wide association studies (TWAS) analysis based on eQTLs. RESULTS: It was shown that the rise of frailty index could increase the risk of psoriasis (IVW, beta = 0.916, OR = 2.500, 95%CI:1.418-4.408, p = 0.002) through Mendelian randomization (MR), and there was no heterogeneity and pleiotropy. There was no causality between the frailty index and other common diseases in dermatology. We found 31 eQTLs based on strongly correlated SNPs in the causality. TWAS analysis found that the expressions of four genes were closely related to psoriasis, including HLA-DQA1, HLA-DQA2, HLA-DRB1 and HLA-DQB1. CONCLUSION: It suggested that the frailty index had a significant positive causality on the risk of psoriasis, which was well documented by combined genomic, transcriptome, and proteome analyses.

2.
Angew Chem Int Ed Engl ; : e202402440, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426574

RESUMO

Perfluoroalkyl substances (PFASs) are persistent and toxic to human health. It is demanding for high-efficient and green technologies to remove PFASs from water. In this study, a novel PFAS treatment technology was developed, utilizing polytetrafluoroethylene (PTFE) particles (1~5 µm) as the catalyst and a low frequency ultrasound (US, 40 kHz, 0.3 W/cm2) for activation. Remarkably, this system can induce near-complete defluorination for different structured PFASs. The underlying mechanism relies on contact electrification between PTFE and water, which induces cumulative electrons on PTFE surface, and creates a high surface voltage (tens of volts). Such high surface voltage can generate abundant reactive oxygen species (ROS, i.e., O2•-, HO•, etc.) and a strong interfacial electrostatic field (IEF of 109~1010 V/m). Consequently, the strong IEF significantly activates PFAS molecules and reduces the energy barrier of O2•- nucleophilic reaction. Simultaneously, the co-existence of surface electrons (PTFE*(e-)) and HO• enables synergetic reduction and oxidation of PFAS and its intermediates, leading to enhanced and thorough defluorination. The US/PTFE method shows compelling advantages of low energy consumption, zero chemical input, and few harmful intermediates. It offers a new and promising solution for effectively treating the PFAS-contaminated drinking water.

3.
Small ; : e2400234, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426650

RESUMO

Investigations concerning the glyoxylate moiety as a photocleavable functional group for visible light photoinitiators, particularly in the initiation of free radical photopolymerization remain limited. This study introduces nine innovative carbazole-based ethyl glyoxylate derivatives (CEGs), which are synthesized and found to exhibit excellent photoinitiation abilities as monocomponent photoinitiating systems. Notably, these structures demonstrate robust absorption in the near-UV/visible range, surpassing the commercial photoinitiators. Moreover, the newly developed glyoxylate derivatives show higher acrylate function conversions compared to a benchmark photoinitiator (MBF) in free radical photopolymerization. Elucidation of the photoinitiation mechanism of CEGs is achieved through a comprehensive analysis involving the decarboxylation reaction and electron spin resonance spin trapping. Furthermore, their practical utility is confirmed during direct laser writing and 3D printing processes, enabling the successful fabrication of 3D printed objects. This study introduces pioneering concepts and effective strategies in the molecular design of novel photoinitiators, showcasing their potential for highly advantageous applications in 3D printing.

4.
Opt Lett ; 49(5): 1121-1124, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426953

RESUMO

Lithium niobate on insulator (LNOI) holds great potential for frequency conversion, where a variety of high-performance nonlinear devices based on different structures has been demonstrated. Here, we report on second harmonic generation (SHG) in MgO-doped LNOI ridge micro-waveguides for efficient green light emission, via an exact type-I noncritical birefringence phase matching (BPM). The LNOI micro-waveguide has a cross section of ∼3×4 µm2, featuring low coupling loss with lens fiber. The normalized conversion efficiency from a continuous-wave (cw) pump to its second harmonic is measured to be 37%/Wcm2 in a single-pass configuration. The device shows both relatively high efficiency and a void of periodic poling, offering a potential solution for efficient and scalable green light sources and frequency converters.

5.
Brain ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38425314

RESUMO

Anti-IgLON5 disease is a rare and likely underdiagnosed subtype of autoimmune encephalitis. The disease displays a heterogeneous phenotype that includes sleep, movement, and bulbar-associated dysfunction. Presence of IgLON5-antibodies in CSF/serum, together with a strong association with HLA-DRB1*10:01∼DQB1*05:01, support an autoimmune basis. In this study, a multicentric HLA study of 87 anti-IgLON5 patients revealed a stronger association with HLA-DQ than HLA-DR. Specifically, we identified a predisposing rank-wise association with HLA-DQA1*01:05∼DQB1*05:01, HLA-DQA1*01:01∼DQB1*05:01 and HLA-DQA1*01:04∼DQB1*05:03 in 85% of patients. HLA sequences and binding cores for these three DQ heterodimers were similar, unlike those of linked DRB1 alleles, supporting a causal link to HLA-DQ. This association was further reflected in an increasingly later age of onset across each genotype group, with a delay of up to 11 years, while HLA-DQ-dosage dependent effects were also suggested by reduced risk in the presence of non-predisposing DQ1 alleles. The functional relevance of the observed HLA-DQ molecules was studied with competition binding assays. These proof-of-concept experiments revealed preferential binding of IgLON5 in a post-translationally modified, but not native, state to all three risk-associated HLA-DQ receptors. Further, a deamidated peptide from the Ig2-domain of IgLON5 activated T cells in two patients, compared to one control carrying HLA-DQA1*01:05∼DQB1*05:01. Taken together, these data support a HLA-DQ-mediated T cell response to IgLON5 as a potentially key step in the initiation of autoimmunity in this disease.

6.
J Org Chem ; 89(5): 2847-2857, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38364825

RESUMO

In recent years, the application of fluorinated alcohols as solvents, cosolvents, or additives has become important in modern organic synthesis. However, their potential as efficient catalysts in organic synthesis has not been well-explored. In this article, we report on the development of a one-pot sequential cascade reaction of p-quinone methides with difluoroenoxysilanes using hexafluoroisopropanol as catalyst. This reaction allows for the preparation of fluorinated multisubstituted oxa-spiro[4,5]cyclohexadienones. By using 50 mol % 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP), the reaction proceeds smoothly to yield 1,6-conjugated products, which are then subjected to oxidative dearomatization/hemiacetalization using PhI(OAc)2. The overall process affords moderate to high yields and excellent diastereoselectivities.

7.
Front Psychiatry ; 15: 1328240, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38362032

RESUMO

Aims: Autism is a multifaceted developmental disorder of the nervous system, that necessitates novel therapeutic approaches beyond traditional medications and psychosomatic therapy, such as appropriate sensory integration training. This systematic mapping review aims to synthesize existing knowledge on enriching environmental interventions as an alternative avenue for improving autism, guiding future research and practice. Method: A comprehensive search using the terms ASD and Enriched Environment was conducted across PubMed, EMBASE, ISI, Cochrane, and OVID databases. Most of the literature included in this review was derived from animal model experiments, with a particular focus on assessing the effect of EE on autism-like behavior, along with related pathways and molecular mechanisms. Following extensive group discussion and screening, a total of 19 studies were included for analysis. Results: Enriched environmental interventions exhibited the potential to induce both behavioral and biochemical changes, ameliorating autism-like behaviors in animal models. These improvements were attributed to the targeting of BDNF-related pathways, enhanced neurogenesis, and the regulation of glial inflammation. Conclusion: This paper underscores the positive impact of enriched environmental interventions on autism through a review of existing literature. The findings contribute to a deeper understanding of the underlying brain mechanisms associated with this intervention.

9.
J Am Chem Soc ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38364093

RESUMO

All-weather operation is considered an ultimate pursuit of the practical development of sodium-ion batteries (SIBs), however, blocked by a lack of suitable electrolytes at present. Herein, by introducing synergistic manipulation mechanisms driven by phosphorus/silicon involvement, the compact electrode/electrolyte interphases are endowed with improved interfacial Na-ion transport kinetics and desirable structural/thermal stability. Therefore, the modified carbonate-based electrolyte successfully enables all-weather adaptability for long-term operation over a wide temperature range. As a verification, the half-cells using the designed electrolyte operate stably over a temperature range of -25 to 75 °C, accompanied by a capacity retention rate exceeding 70% even after 1700 cycles at 60 °C. More importantly, the full cells assembled with Na3V2(PO4)2O2F cathode and hard carbon anode also have excellent cycling stability, exceeding 500 and 1000 cycles at -25 to 50 °C and superb temperature adaptability during all-weather dynamic testing with continuous temperature change. In short, this work proposes an advanced interfacial regulation strategy targeted at the all-climate SIB operation, which is of good practicability and reference significance.

10.
Vet Microbiol ; 291: 110013, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38364468

RESUMO

Potassium diformate (KDF) is a kind of formate, which possesses the advantages of antimicrobial activity, growth promotion and preventing diarrhea in weaned piglets. However, the researches of KDF in animal production mostly focused on apparent indexes such as growth performance and the mechanisms of KDF on intestinal health have not been reported. Thus, porcine small intestinal epithelial cells (IPEC-J2) infected with Enterohemorrhagic Escherichia coli (EHEC) was used to investigate the role of KDF on alleviating intestinal inflammation in this study. The 0.125 mg/mL KDF treated IPEC-J2 cells for 6 h and IPEC-J2 cells challenged with 5 × 107 CFU/mL EHEC for 4 h were confirmed as the optimum concentration and time for the following experiment. The subsequent experiment was divided into four groups: control group (CON), EHEC group, KDF group, KDF+EHEC group. The results showed that KDF increased the cell viability and the gene expression levels of SGLT3 and TGF-ß, while decreased the content of IL-1ß compared with the CON group. The cell viability and the gene expressions of SGLT1, SGLT3, GLUT2, Claudin-1, Occludin and TGF-ß, and the protein expression of ZO-1 in EHEC group were lower than those in CON group, whereas the gene expressions of IL-1ß, TNF, IL-8 and TLR4, and the level of phosphorylation NF-кB protein were increased. Pretreatment with KDF reduced the content of IgM and IL-1ß, the gene expressions of IL-1ß, TNF, IL-8 and TLR4 and the level of phosphorylation NF-кB protein, and increased the gene expression of TGF-ß and the protein expression of Occludin in IPEC-J2 cells infected EHEC. In conclusion, 0.125 mg/mL KDF on IPEC-J2 cells for 6 h had the beneficial effects on ameliorating the intestinal inflammation because of reduced pro-inflammatory cytokines and enhanced anti-inflammatory cytokines through regulating NF-кB signaling pathway under the EHEC challenge.

11.
Clin Nucl Med ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38377375

RESUMO

ABSTRACT: We compared 18F-FAPI and 18F-FDG PET/CT findings of metastatic perivacular epitheliod cell tumor in a 23-year-old woman. Apart from showing strong uptake of a left upper lung mass that showed moderate uptake on 18F-FDG, 18F-FAPI PET/CT additionally presented hypermetabolism in diffuse multifocal lesion throughout the body. This case suggests that 18F-FAPI PET/CT might play a more beneficial role than 18F-FDG PET/CT in identifying and assessing the extent of perivascular epithelioid cell tumors.

12.
Ecotoxicol Environ Saf ; 273: 116106, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38377782

RESUMO

Silica nanoparticle (SiNP) exposure induces severe pulmonary inflammation and fibrosis, but the pathogenesis remains unclear, and effective therapies are currently lacking. To explore the mechanism underlying SiNPs-induced pulmonary fibrosis, we constructed in vivo silica exposure animal models and in vitro models of silica-induced macrophage pyroptosis and fibroblast transdifferentiation. We found that SiNP exposure elicits upregulation of pulmonary proteins associated with pyroptosis, including NLRP3, ASC, IL-1ß, and GSDMD, while the immunofluorescence staining co-localized NLRP3 and GSDMD with macrophage-specific biomarker F4/80 in silica-exposed lung tissues. However, the NLRP3 inhibitor MCC950 and classical anti-fibrosis drug pirfenidone (PFD) were found to be able to alleviate silica-induced collagen deposition in the lungs. In in vitro studies, we exposed the fibroblast to a conditioned medium from silica-induced pyroptotic macrophages and found enhanced expression of α-SMA, suggesting increased transdifferentiation of fibroblast to myofibroblast. In line with in vivo studies, the combined treatment of MCC950 and PFD was demonstrated to inhibit the expression of α-SMA and attenuate fibroblast transdifferentiation. Mechanistically, we adopted high throughput RNA sequencing on fibroblast with different treatments and found activated signaling of relaxin and osteoclast differentiation pathways, where the expression of the dysregulated genes in these two pathways was examined and found to be consistently altered both in vitro and in vivo. Collectively, our study demonstrates that SiNP exposure induces macrophage pyroptosis, which subsequently causes fibroblast transdifferentiation to myofibroblasts, in which the relaxin and osteoclast differentiation signaling pathways play crucial roles. These findings may provide valuable references for developing new therapies for pulmonary fibrosis.

14.
J Am Chem Soc ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381858

RESUMO

Actuating materials convert different forms of energy into mechanical responses. To satisfy various application scenarios, they are desired to have rich categories, novel functionalities, clear structure-property relationships, fast responses, and, in particular, giant and reversible shape changes. Herein, we report a phase transition-driven ferroelectric crystal, (rac-3-HOPD)PbI3 (3-HOPD = 3-hydroxypiperidine cation), showing intriguingly large and anisotropic room-temperature actuating behaviors. The crystal consists of rigid one-dimensional [PbI3] anionic chains running along the a-axis and discrete disk-like cations loosely wrapping around the chains, leaving room for anisotropic shape changes in both the b- and c-axes. The shape change is switched by a ferroelectric phase transition occurring at around room temperature (294 K), driven by the exceptionally synergistic order-disorder and displacive phase transition. The rotation of the cations exerts internal pressure on the stacking structure to trigger an exceptionally large displacement of the inorganic chains, corresponding to a crystal lattice transformation with length changes of +24.6% and -17.5% along the b- and c-axis, respectively. Single crystal-based prototype devices of circuit switches and elevators have been fabricated by exploiting the unconventional negative temperature-dependent actuating behaviors. This work provides a new model for the development of multifunctional mechanically responsive materials.

16.
Shock ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38369528

RESUMO

BACKGROUND: Slaine solution (NSS) and Ringer's acetate solution (RAS) are commonly given to critical ill patients as a fundamental fluid therapy. However, the effect of RAS and NSS on sepsis patient outcomes remains unknown. METHODS: We conducted a single-center prospective open-label parallel controlled trial to enroll adult patients (>18 years old) diagnosed with sepsis. Participants received either RAS or NSS for intravenous infusion for 5 days. The primary outcome was the incidence of Major adverse kidney events within 28 days (MAKE28). Secondary outcomes included 30-/90-day mortality, acute kidney injury (AKI), and hyperchloremia. The patients were then reclassified as NSS-only, RAS-only, and RAS+NSS groups according to the type of fluid they had received before enrollment. Thereafter, a secondary post hoc analysis was performed. RESULTS: 255 septic patients were screened and 143 patients (51.0% in RAS group and 49.0% in NSS group) were enrolled in the study. Each group received a median 2 L of fluid administration during 5 interventional days. 39.3% of patients had received 500 (500-1000) mL of balanced salt solutions (BSSs) prior to ICU admission. There was no statistical difference among the RAS and NSS group on the primary outcome MAKE28 in the initial analysis (23.3% vs. 20.0%, OR1.2 [0.6 to 2.2], p = 0.69). MAKE28 was observed in 23.3% of RAS-only versus 27.3% of NSS-only group patients (0.82 [0.35-1.94], P = 0.65) in the secondary post hoc analysis. The patients in NSS-only group had a longer Invasive Mechanical Ventilation days and a trend toward the accumulation of serum chloride. CONCLUSION: This study observed no statistically significant difference on MAKE28 and secondary outcomes among sepsis patients receiving RAS and NSS. However, it is unclear whether the large amount of fluid resuscitation prior to ICU admission and carrier NSS narrowed the difference between BSSs and NSSs.

17.
J Am Chem Soc ; 146(6): 3974-3983, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38299512

RESUMO

Biologics, including proteins and antisense oligonucleotides (ASOs), face significant challenges when it comes to achieving intracellular delivery within specific organs or cells through systemic administrations. In this study, we present a novel approach for delivering proteins and ASOs to liver cells, both in vitro and in vivo, using conjugates that tether N-acetylated galactosamine (GalNAc)-functionalized, cell-penetrating polydisulfides (PDSs). The method involves the thiol-bearing cargo-mediated ring-opening polymerization of GalNAc-functionalized lipoamide monomers through the so-called aggregation-induced polymerization, leading to the formation of site-specific protein/ASO-PDS conjugates with narrow dispersity. The hepatocyte-selective intracellular delivery of the conjugates arises from a combination of factors, including first GalNAc binding with ASGPR receptors on liver cells, leading to cell immobilization, and the subsequent thiol-disulfide exchange occurring on the cell surface, promoting internalization. Our findings emphasize the critical role of the close proximity of the PDS backbone to the cell surface, as it governs the success of thiol-disulfide exchange and, consequently, cell penetration. These conjugates hold tremendous potential in overcoming the various biological barriers encountered during systemic and cell-specific delivery of biomacromolecular cargos, opening up new avenues for the diagnosis and treatment of a range of liver-targeting diseases.


Assuntos
Produtos Biológicos , Galactosamina , Galactosamina/química , Hepatócitos/metabolismo , Oligonucleotídeos Antissenso/química , Dissulfetos/metabolismo , Compostos de Sulfidrila/metabolismo , Produtos Biológicos/metabolismo
18.
Aging (Albany NY) ; 16(3): 2736-2752, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38309290

RESUMO

Circular RNA (circRNA) is a novel type of RNA that plays an important role in the occurrence and development of many malignant tumors. However, the potential regulatory role and molecular mechanisms of circRNAs in cervical cancer (CC) are still not clear. Here, we explored circRNAs associated with CC from the Gene Expression Omnibus (GEO) datasets GSE113696 and GSE102686. We initially identified circ_0039787, which is derived from exons 2 to 3 of the C16orf70 gene. We observed that circ_0039787 is mainly located in the cytoplasm and is more stable than its linear counterpart, C16orf70. circ_0039787 is significantly upregulated in CC tissues and cells. In addition, functional gain and loss experiments demonstrated that circ_0039787 promotes the proliferation, migration, and invasion of CC cells in vitro and the growth of CC tumors in vivo. Mechanistically, circ_0039787 promotes CC tumor progression by competitively absorbing miR-877-5p to alleviate the inhibitory effect of miR-877-5p on Kirsten Rat Sarcoma viral oncogene homolog (KRAS) expression. Overall, our results suggest that circ_0039787 could serve as a promising diagnostic biomarker and potential therapeutic target for CC patients.


Assuntos
MicroRNAs , Neoplasias do Colo do Útero , Feminino , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias do Colo do Útero/patologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Carcinogênese/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética
19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(1): 183-189, 2024 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-38322527

RESUMO

Objective: To develop a catalytic hairpin assembly (CHA)-based fluorescent assay for the detection of the target RNA of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), so as to realize the rapid nucleic acid testing of SARS-CoV-2. Methods: A 24-nt segment of the SARS-CoV-2 nucleocapsid protein gene (N gene, NC_045512.2) was chosen as the target RNA and the hairpin motif 1 (H1) and hairpin motif 2 (H2) were designed based on the principle of CHA reaction. The H1 motif was labelled with a fluorophore group as well as a quencher group. When the target RNA was added to the hairpin motifs, CHA reaction was triggered at room temperature (25 ℃), which led to the amplification of fluorescence signal, thereby enabling the rapid detection of the target RNA. After the optimization of the hairpin motifs and the experimental conditions, the sensitivity and the specificity of the testing method were measured to evaluate its performance. Results: We successfully constructed a CHA-based fluorescent assay specifically for the target RNA of SARS-CoV-2. With this method, testing could be completed at room temperature within 30 min. This testing method exhibited excellent specificity and could be used to accurately distinguish the perfectly-matched target RNA from the target RNA with single-base mutations. In addition, the testing method demonstrated good sensitivity, with a detection limit of 50 pmol/L. Conclusion: The proposed assay enables the simple and rapid detection of the SARS-CoV-2 target RNA with excellent sensitivity and specificity, showing great promise for further optimization and subsequent clinical application for the rapid detection of SARS-CoV-2 nucleic acid.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Sensibilidade e Especificidade , RNA , Técnicas de Amplificação de Ácido Nucleico/métodos
20.
Diabetes Metab Syndr Obes ; 17: 633-646, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38343583

RESUMO

Objective: Gestational diabetes mellitus (GDM) is a condition of glucose intolerance, which may be accompanied with inflammation. The levels of hematological parameters during pregnancy can reflect inflammatory conditions in pregnant women. This study aims to describe the dynamic change of blood cell parameters from the first trimester (6-12 weeks of gestation) to the second trimester (24-28 weeks of gestation) and to investigate the associations of these biomarkers with the risk of GDM. Methods: This study was a prospective double-center study conducted in Beijing, China (clinical trial number: NCT03246295). Hematological parameters were tested four times during the follow-up. Logistic regression analysis and Receiver Operating Characteristic (ROC) curve analysis were used to explore the association and predictive ability of hematological parameters for GDM. Results: There were 258 of 1027 pregnant women in our study developed GDM. Among the 1027 pregnant women, white blood cells (WBC) gradually increased, and red blood cells (RBC), hemoglobin (HGB), and platelet (PLT) tended to decrease from the first trimester to second trimester. After adjusting for confounding factors, higher levels of RBC, HGB, and PLT in both early and middle pregnancy were positively associated with GDM risk, whereas the level of WBC was associated with GDM risk only in early pregnancy. WBC, RBC, HGB, and PLT in early and middle pregnancy were all correlated with fasting insulin (FINS) in early pregnancy. Conclusion: Higher levels of hematological parameters in early and middle pregnancy were associated with glucose metabolism in early pregnancy and the subsequent risk of GDM.

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