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1.
Org Lett ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633182

RESUMO

An efficient kinetic resolution of sulfinamides via an asymmetric N-allylic alkylation reaction was realized using hydroquinine as a catalyst under mild conditions. The kinetic resolution of a range of Morita-Baylis-Hillman adducts and N-aryl tert-butylsulfinamides was highly effective. In addition, the synthetic utility of the protocol was demonstrated by a scaled-up reaction. Density functional theory calculations provide convincing evidence for the interpretation of stereoselection.

2.
Entropy (Basel) ; 23(10)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34682052

RESUMO

Based on elastic mechanics, the fluid-structure coupling theory and the finite element method, a high-speed railway wheel-rail rolling-aerodynamic noise model is established to realize the combined simulation and prediction of the vibrations, rolling noise and aerodynamic noise in wheel-rail systems. The field test data of the Beijing-Shenyang line are considered to verify the model reliability. In addition, the directivity of each sound source at different frequencies is analyzed. Based on this analysis, noise reduction measures are proposed. At a low frequency of 300 Hz, the wheel-rail area mainly contributes to the aerodynamic noise, and as the frequency increases, the wheel-rail rolling noise becomes dominant. When the frequency is less than 1000 Hz, the radiated noise fluctuates around the cylindrical surface, and the directivity of the sound is ambiguous. When the frequency is in the middle- and high-frequency bands, exceeding 1000 Hz, both the rolling and total noise exhibit a notable directivity in the directions of 20-30° and 70-90°, and thus, noise reduction measures can be implemented in these directions.

3.
Nano Lett ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623162

RESUMO

The formation of membrane nanopores is one of the crucial activities of cells and has attracted considerable attention. However, the understanding of their types and mechanisms is still limited. Herein, we report a novel nanopore formation phenomenon achieved through the insertion of polymeric nanotoroids into the cellular membrane. As revealed by theoretical simulations, the nanotoroid can embed in the membrane, leaving a nanopore on the cell. The through-the-cavity wrapping of lipids is critical for the retention of the nanotoroid in the membrane, which is attributed to both a relatively large inner cavity of the nanotoroid and a moderate attraction between the nanotoroid and membrane lipids. Under the guidance of the simulation predictions, experiments using polypeptide toroids as pore-forming agents were performed, confirming the unique biophysical phenomenon. This work demonstrates a distinctive pore-forming pathway, deepens the understanding of the membrane nanopore phenomenon, and assists in the design of advanced pore-forming materials.

4.
J Hazard Mater ; 416: 126069, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492895

RESUMO

Concerns that airborne microplastics (MP) may be detrimental to human health are rising. However, research on the effects of MP on the respiratory system are limited. We tested the effect of MP exposure on both normal and asthmatic pulmonary physiology in mice. We show that MP exposure caused pulmonary inflammatory cell infiltration, bronchoalveolar macrophage aggregation, increased TNF-α level in bronchoalveolar lavage fluid (BALF), and increased plasma IgG1 production in normal mice. MP exposure also affected asthma symptoms by increasing mucus production and inflammatory cell infiltration with notable macrophage aggregation. Further, we found co-labeling of macrophage markers with MP incorporating fluorescence, which indicates phagocytosis of the MP by macrophages. A comparative transcriptomic analysis showed that MP exposure altered clusters of genes related to immune response, cellular stress response, and programmed cell death. A bioinformatics analysis further uncovered the molecular mechanism whereby MP stimulated production of tumor necrosis factor and immunoglobulins to activate a group of transmembrane B-cell antigens, leading to the modulation of cellular stress and programmed cell death in the asthma model. In summary, we show that MP exposure had detrimental effects on the respiratory system in both healthy and asthmatic mice, which calls for urgent discourse and action to mitigate environmental microplastic pollutants.


Assuntos
Asma , Microplásticos , Animais , Asma/induzido quimicamente , Líquido da Lavagem Broncoalveolar , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Plásticos
5.
Mater Sci Eng C Mater Biol Appl ; 128: 112347, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474897

RESUMO

Although the use of bioactive ions and proteins are crucial for bone defect repair, delivering them in a stable and controlled manner remains challenging. To achieve controlled delivery of osteogenic active factor, we developed a novel double network (DN) hydrogel capable of co-delivering Mg2+ ions and BMP2 in a controlled localized manner. This DN hydrogel was composed of poly (acrylamide) and chitosan, in which the poly (acrylamide) was cross-linked via covalent bond and the chitosan was grafted using bisphosphonate (BP) to form metal coordination bonds with Mg2+ ions. Due to this dynamic dissociation and re-association of the "BP-Mg2+" coordination bond, it was possible to deliver Mg2+ ions in a stable and controlled manner. Additionally, the obtained DN hydrogel exhibited an effective tensile strength (0.62 MPa), perfect stretchability (973% fracture strain), and good creep and recovery properties due to the dynamic cross-linking effect of "BP-Mg2+". Additionally, the hydrogel could synergistically promote the proliferation and differentiation of mouse embryo osteoblast precursor cells (MC3T3-E1 cells) in vitro via the BMP2/Wnt pathway. In the skull defect rat model, this positive delivery government of Mg2+ ions and BMP2 synergistically accelerated bone regeneration. In conclusion, this dynamic cross-linked hydrogel containing Mg2+ ions established a new platform for the sustained release of osteogenesis factor and accelerated the bone regeneration process.


Assuntos
Hidrogéis , Magnésio , Animais , Proteína Morfogenética Óssea 2 , Regeneração Óssea , Diferenciação Celular , Íons , Camundongos , Osteogênese , Ratos
6.
Nanoscale ; 13(33): 14016-14022, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34477682

RESUMO

Spiral nanostructures, mainly in the 2D form, have been observed in polymer self-assembly, while well-defined 3D spirals are rarely reported. Here we report that a binary system containing polypeptide-based block copolymers and homopolymers can self-assemble into well-defined spiral spheres (3D spirals), in which the homopolymers form the core and the copolymers form the spirals. Upon increasing the preparation temperature, meridian spheres were obtained. Mixing polypeptide block copolymers with opposite backbone chirality also leads to the formation of meridian spheres. In the meridian patterns, a tighter packing manner of the phenyl groups appended to the polypeptide blocks was observed, which is responsible for the spiral-to-meridian transitions. This work enriches the research of spiral assemblies and provides a facile route to switch chiral/achiral nanostructures by regulating the packing manner of the pendant groups.

7.
Front Cell Dev Biol ; 9: 730380, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485309

RESUMO

Runt-related transcription factors (RUNXs) can serve as both transcription activators and repressors during biological development, including immune cell maturation. RUNX factors have both tumor-promoting and tumor-suppressive roles in carcinogenesis. Immune cell infiltration and the tumor immune microenvironment have been found to be key regulators in breast cancer progression, treatment response, and patient outcome. However, the relationship between the RUNX family and immune cell infiltration in breast cancer remains unclear. We performed a comprehensive analysis to reveal the role of RUNX factors in breast cancer. Analysis of patient data in the Oncomine database showed that the transcriptional levels of RUNX proteins in breast cancer were elevated. Kaplan-Meier plotter (KM plotter) analysis showed that breast cancer patients with higher expression of RUNX proteins had better survival outcomes. Through analysis of the UALCAN database, we found that the transcriptional levels of RUNX factors were significantly correlated with some breast cancer patient characteristics. cBio Cancer Genomics Portal (cBioPortal) analysis showed the proportions of different RUNX genomic alterations in various subclasses of breast cancer. We also performed gene ontology (GO) and pathway analyses for the significantly differentially expressed genes that were correlated with RUNX factors in breast cancer. TIMER database analysis showed that immune cell infiltration in breast cancer could be affected by the transcriptional level, mutation, and gene copy number of RUNX proteins. Using the Gene Set Cancer Analysis (GSCA) database, we analyzed the effects of RUNX gene methylation on the level of immune cell infiltration in breast cancer. We found that the methylation level changes of RUNX2 and RUNX3 had opposite effects on immune cell infiltration in breast cancer. We also analyzed the relationship between the methylation level of RUNX genes and the TGF-ß signaling pathway using the TISIDB database. The results showed that the methylation levels of RUNX1 and RUNX3 were correlated with the expression of TGF-ß1. In summary, our analysis found that the RUNX family members can influence the infiltration of various immune cells in breast cancer depending on their expression level, mutation, gene copy number, and methylation. The RUNX family is an important regulator of immune cell infiltration in breast cancer and may serve as a potential prognostic biomarker.

8.
J Periodontal Res ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34514591

RESUMO

OBJECTIVE: To evaluate the influence of diverse anti-rheumatic agents on the periodontal condition and to provide clinical medication guidance for patients with rheumatoid arthritis (RA) and periodontitis. BACKGROUND: In recent years, the correlation between RA and periodontitis has become a hot research topic, but no medication recommendations for patients with RA and periodontitis are available at present. METHODS: The protocol of this review was registered in advance with PROSPERO (CRD42021248827). Electronic search and manual searches up to March 20, 2021 were conducted. The inclusion criteria for the studies were as follows: included patients diagnosed with periodontitis and RA submitted to anti-rheumatic agent therapy; with a control group receiving no anti-rheumatic agent therapy; with outcomes including at least one periodontal parameter. Probing depth (PD) and clinical attachment loss (CAL) were pooled using weighted mean difference (WMD) and 95% confidence intervals (CI) while gingival index (GI)/modified gingival index (MGI) was analyzed by standardized mean difference (SMD) and 95% CI. RESULTS: One thousand four hundred and seventy-eight studies potentially related to the aim of this review were screened, but only 463 patients from 14 studies were included in the qualitative analysis, and 146 patients from 4 studies were included in the meta-analysis. Statistically significant reductions were observed among the subjects who received anti-rheumatic agents for PD [WMD = -0.20; 95% CI (-0.33, -0.07); effect p = .003; I2  = 50%; p = .11], CAL [WMD = -0.4; 95% CI (-0.66, -0.15); effect p = .002; I2  = 57%; p = .07] and GI/MGI [SMD = -0.61;95% CI (-0.94, -0.27; effect p = .0004; I2  = 26%; p = .25]. Consistent with the above results, this systematic review produced promising results that PD, CAL, GI/MGI, and bleeding on probing (BOP) decreased when patients with RA and periodontitis were treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), anti-B lymphocyte agents, anti-IL-6R agents, or JAK inhibitors. PD and CAL declined after the administration of anti-TNF-α agents; most studies reported decreased GI/MGI and BOP, while 2 studies reported increased GI/MGI and BOP. CONCLUSIONS: These results revealed that csDMARDs, anti-B lymphocyte agents, anti-IL-6R agents, anti-TNF-α agents, and JAK inhibitors had potential positive effects in improving the periodontal condition of patients with RA and periodontitis. However, future research is needed to elucidate whether anti-TNF-α agents have a side effect of increased gingival inflammation.

9.
J Am Chem Soc ; 143(36): 14684-14693, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34472352

RESUMO

Anchorage-dependent contact-inhibited growth usually refers to on-surface cell proliferation inhibited by the proximity of other cells. This phenomenon, prominent in nature, has yet to be achieved with polymeric micelles. Here, we report the control living supra-macromolecular self-assembly of elongated micelles with a liquid crystalline core onto a hydrophobic substrate via the synergetic interactions between the substrate and aggregates dispersed in solution. In this system, seed formation is a transient phenomenon induced by the adsorption and rearrangement of the core-swollen aggregates. The seeds then trigger the growth of elongated micelles onto the substrate in a living controllable manner until the contact with the substrate is disrupted. Brownian dynamic simulations show that this unique behavior is due to the fusion of the aggregates onto both ends of the anchored seeds. More important, the micelle length can be tuned by varying the substrate hydrophobicity, a key step toward the fabrication of intricate structures.

10.
J Am Chem Soc ; 143(39): 16095-16104, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34558894

RESUMO

Breaking the symmetry of a crystal structure can enable even-order nonlinear activities, including second-harmonic generation (SHG). The emerging chiral hybrid organic-inorganic metal halides feature unique optical and electronic properties and flexible crystal structures, making them a class of promising nonlinear optical materials. However, their nonlinear response performances are currently inferior to traditional nonlinear crystals, because of the lack of research on resonant enhancement and third-harmonic generation (THG). Herein, we designed chiral hybrid bismuth halides with naturally nonsymmetrical structure to enable SHG. Simultaneously, these chiral compounds preserve 1D crystal structures to create strong free exciton, broad self-trapped exciton (STE), and discrete band energy levels, which facilitate the resonant enhancement of SHG and THG susceptibilities. These new chiral films showcase superior effective SHG susceptibility (χ(2) ∼ 130.5 pm V-1 at an interesting wavelength of 1550 nm), exceeding that of the reference, a commercial LiNbO3 (χ(2) ∼ 83.4 pm V-1) single-crystal film. Furthermore, their THG intensities are even higher than their SHG intensities, with effective THG susceptibility (χ(3)) being ∼9.0 × 106 pm2 V-2 at 1550 nm (37 times that of the reference monolayer WS2). Their high SHG and THG performances indicate the promising future of these 1D chiral hybrid bismuth halides toward nonlinear optical applications.

11.
Comput Math Methods Med ; 2021: 5990999, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557257

RESUMO

Artificial Intelligence (AI) is the domain of computer science that focuses on the development of machines that operate like humans. In the field of AI, medical disease detection is an instantly growing domain of research. In the past years, numerous endeavours have been made for the improvements of medical disease detection, because the errors and problems in medical disease detection cause serious wrong medical treatment. Meta-heuristic techniques have been frequently utilized for the detection of medical diseases and promise better accuracy of perception and prediction of diseases in the domain of biomedical. Particle Swarm Optimization (PSO) is a swarm-based intelligent stochastic search technique encouraged from the intrinsic manner of bee swarm during the searching of their food source. Consequently, for the versatility of numerical experimentation, PSO has been mostly applied to address the diverse kinds of optimization problems. However, the PSO techniques are frequently adopted for the detection of diseases but there is still a gap in the comparative survey. This paper presents an insight into the diagnosis of medical diseases in health care using various PSO approaches. This study presents to deliver a systematic literature review of current PSO approaches for knowledge discovery in the field of disease detection. The systematic analysis discloses the potential research areas of PSO strategies as well as the research gaps, although, the main goal is to provide the directions for future enhancement and development in this area. This paper gives a systematic survey of this conceptual model for the advanced research, which has been explored in the specified literature to date. This review comprehends the fundamental concepts, theoretical foundations, and conventional application fields. It is predicted that our study will be beneficial for the researchers to review the PSO algorithms in-depth for disease detection. Several challenges that can be undertaken to move the field forward are discussed according to the current state of the PSO strategies in health care.

12.
J Sci Food Agric ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523722

RESUMO

BACKGROUND: Recent studies demonstrate that fish byproducts can be used as sources of bioactive peptides for functional foods. Sturgeon skin contains abundant proteins but it has commonly been discarded during sturgeon processing. The objective of the present work was to identify and characterize the bioactive peptides from protein hydrolysates of sturgeon skin. RESULTS: Sturgeon skin protein extract (SKPE) hydrolyzed by flavourzyme for 60 min exhibited high antioxidant activity, dipeptidyl peptidase IV (DPP-IV) and angiotensin converting enzyme (ACE) inhibitory activity. The sequences of peptides from flavourzyme hydrolysates were identified using high-performance liquid chromatography-tandem mass spectrometry. Gly-Asp-Arg-Gly-Glu-Ser-Gly-Pro-Ala (P1) showed the highest DPPH radical scavenging activity (DPPH IC50  = 1.93 mmol L-1 ). Gly-Pro-Ala-Gly-Glu-Arg-Gly-Glu-Gly-Gly-Pro-Arg (P11) (DPP-IV IC50  = 2.14 mmol L-1 ) and Ser-Pro-Gly-Pro-Asp-Gly-Lys-Thr-Gly-Pro-Arg (P12) (DPP-IV IC50  = 2.61 mmol L-1 ) exhibited the strongest DPP-IV inhibitory activity. Gly-Pro-Pro-Gly-Ala-Asp-Gly-Gln-Ala-Gly-Ala-Lys (P6) displayed the highest ACE inhibitory activity (ACE IC50  = 3.77 mmol L-1 ). The molecular docking analysis revealed that DPP-IV inhibition of P11 and P12 are mainly attributed to hydrogen bonds and hydrophobic interactions, whereas ACE inhibition of P6 is mainly attributed to strong hydrogen bonds. CONCLUSIONS: These results indicate that SKPE hydrolysates generated by flavourzyme are potential sources of bioactive peptides that could be used in the health food industry. © 2021 Society of Chemical Industry.

13.
Materials (Basel) ; 14(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576610

RESUMO

In this paper, a full-cycle interactive progressive (FIP) method that integrates topology optimization, parametric optimization, and experimental analysis to determine the optimal energy absorption properties in the design of chiral mechanical metamaterials is proposed. The FIP method has improved ability and efficiency compared with traditional design methods due to strengthening the overall design, introducing surrogate models, and its consideration of the application conditions. Here, the FIP design was applied in the design of mechanical metamaterials with optimized energy absorption properties, and a chiral mechanical metamaterial with good energy absorption and impact resistance was obtained based on the rotation mechanism of metamaterials with a negative Poisson's ratio. The relationship among the size parameters, applied boundary conditions, and energy absorption properties were studied. An impact compression experiment using a self-made Fiber Bragg Grating sensor was carried out on the chiral mechanical metamaterial. In light of the large deviation of the experimental and simulation data, a feedback adjustment was carried out by adjusting the structural parameters to further improve the mechanical properties of the chiral mechanical metamaterial. Finally, human-computer interaction, self-innovation, and a breakthrough in the design limits of the optimized model were achieved. The results illustrate the effectiveness of the FIP design method in improving the energy absorption properties in the design of chiral mechanical metamaterials.

14.
Int J Oral Sci ; 13(1): 28, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34475379

RESUMO

Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis, has been shown to accelerate the progression of atherosclerosis (AS). However, the definite mechanisms remain elusive. Emerging evidence supports an association between mitochondrial dysfunction and AS. In our study, the impact of P. gingivalis on mitochondrial dysfunction and the potential mechanism were investigated. The mitochondrial morphology of EA.hy926 cells infected with P. gingivalis was assessed by transmission electron microscopy, mitochondrial staining, and quantitative analysis of the mitochondrial network. Fluorescence staining and flow cytometry analysis were performed to determine mitochondrial reactive oxygen species (mtROS) and mitochondrial membrane potential (MMP) levels. Cellular ATP production was examined by a luminescence assay kit. The expression of key fusion and fission proteins was evaluated by western blot and immunofluorescence. Mdivi-1, a specific Drp1 inhibitor, was used to elucidate the role of Drp1 in mitochondrial dysfunction. Our findings showed that P. gingivalis infection induced mitochondrial fragmentation, increased the mtROS levels, and decreased the MMP and ATP concentration in vascular endothelial cells. We observed upregulation of Drp1 (Ser616) phosphorylation and translocation of Drp1 to mitochondria. Mdivi-1 blocked the mitochondrial fragmentation and dysfunction induced by P. gingivalis. Collectively, these results revealed that P. gingivalis infection promoted mitochondrial fragmentation and dysfunction, which was dependent on Drp1. Mitochondrial dysfunction may represent the mechanism by which P. gingivalis exacerbates atherosclerotic lesions.


Assuntos
Dinâmica Mitocondrial , Porphyromonas gingivalis , Células Endoteliais , Mitocôndrias
15.
Onco Targets Ther ; 14: 4545-4550, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34466000

RESUMO

Background: Myelomatous pleural effusion (MPE), as a presentation of extramedullary infiltration of multiple myeloma (MM), is rare and currently associated with poor outcomes without effective therapy. The potential value of cytokine detection in pleural effusion to MPE has not been reported to date. Case Presentation: We herein report a case of refractory and relapsed multiple myeloma that developed bilateral MPE due to disease progression caused by intolerance to various chemotherapy regimens. Cytomorphology and flow cytometry were adopted for diagnosis confirmation. Chemotherapy containing immunomodulators combined with thoracic catheterization drainage was applied to the patient, showing a certain therapeutic effect. During the course of disease, the change of cytokine profile in pleural effusion was monitored by cytometric bead array (CBA) technology, revealing that cytokines related to tumor load such as interleukin 6 (IL-6) and interleukin 10 (IL-10) in pleural effusion decreased with the improvement of disease, while other cytokines such as interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 17A (IL-17A), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), granzyme A, granzyme B, perforin and granulysin increased with the improvement of disease. Conclusion: There is a prospect that cytokine level in pleural effusion may indicate treatment response of MPE, and in light of this case, immunomodulators may be utilized in treating patients suffering MPE. Due to limitations of our single case, we urge more groups to evaluate the potential role of cytokine profile in MPE.

16.
Small ; : e2102340, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561947

RESUMO

Solution-processed colloidal quantum dots (CQDs) are promising candidates for the third-generation photovoltaics due to their low cost and spectral tunability. The development of CQD solar cells mainly relies on high-quality CQD ink, smooth and dense film, and charge-extraction-favored device architectures. In particular, advances in the processing of CQDs are essential for high-quality QD solids. The phase transfer exchange (PTE), in contrast with traditional solid-state ligand exchange, has demonstrated to be the most promising approach for high-quality QD solids in terms of charge transport and defect passivation. As a result, the efficiencies of Pb chalcogenide CQD solar cells have been rapidly improved to 14.0%. In this review, the development of the PTE method is briefly reviewed for lead chalcogenide CQD ink preparation, film assembly, and device construction. Particularly, the key roles of lead halides and additional additives are emphasized for defect passivation and charge transport improvement. In the end, several potential directions for future research are proposed.

17.
Adv Mater ; 33(38): e2101903, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34342910

RESUMO

Flat panel displays enjoy 100 billion-dollar markets with significant penetration in daily life, which require efficient, color-saturated blue, green, and red light-emitting diodes (LEDs). The recently emerged halide perovskites have demonstrated low-cost and outstanding performance for potential LED applications. However, the performance of blue perovskite LEDs (PeLEDs) lags far behind red and green cousins, particularly for color coordinates approaching (0.131, 0.046) that fulfill the Rec. 2020 specification for blue emitters. Here, a high-efficiency, lead-free perovskite, CsEuBr3 , is reported that exhibits bright blue exciton emission centered at 448 nm with a color coordinates of (0.15, 0.04), contributed from Eu-5d→Eu-4f/Br-4p transition with an optical band gap of 2.85 eV. Further optical characterizations reveal its short excited-state lifetime of 151 ns, excellent exciton diffusion diffusivity of 0.0227 cm2 s-1 , and high quantum yield of ≈69%. Inspired by these findings, deep-blue PeLEDs based on all-vacuum processing methods, which have been demonstrated as the most successful approach for the organic LED industry, are constructed. The devices show a maximum external quantum efficiency of 6.5% with an operating half-lifetime of 50 mins at an initial brightness of 15.9 cd m-2 . It is anticipated that this work will inspire further research on lanthanide-based perovskites for next-generation LED applications.

18.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(3): 225-229, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34374231

RESUMO

Objective: To investigate the relationship between mitochondrial DNA (mtDNA) variation and high altitude essential hypertension(HAEH) in the Chinese Tajik population. Methods: Fifty-three patients with HAEH and 46 healthy subjects were enrolled from the Chinese Tajik population. The mtDNA fragments were amplificated by polymerase chain reaction, and products were sequenced to acquire full sequence of mtDNA. The mtDNA sequences of all subjects were compared to the Cambridge sequence to explore mtDNA variations and analyze difference between HAEH and healthy controls. Online softwares were applied to predict function changes caused by positive associated mtDNA variations. Results: Compared to the control group, the frequency of haplogroup U4b was significant higher in HAEH group(P=0.023,OR=7.062,CI(95%)=1.306-38.182), and the frequencies of 8 mutations from haplogroup U4b showed a significant difference between the HAEH group and control group (all with P values below 0.05). The mt DNA15693T>C mutation was the only missense mutation, which affected amino acid 316 in mitochondrial cytochrome b (MTCYB) by changing it from methionine to threonine. Bioinformatics analysis indicated that the mutation in MTCYB may play a biological role through affecting the second structure of protein. Conclusion: MtDNA subhaplogroup U4b is a genetic factor for HAEH in the Chinese Tajik population, and mtDNA15693T>C mutation may be an important molecular mechanism of HAEH.


Assuntos
DNA Mitocondrial , Predisposição Genética para Doença , Altitude , Grupo com Ancestrais do Continente Asiático/genética , China , DNA Mitocondrial/genética , Hipertensão Essencial/genética , Haplótipos , Humanos , Mutação
19.
J Am Chem Soc ; 143(34): 13675-13685, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34410121

RESUMO

Polymer-based room-temperature phosphorescence (RTP) materials with high flexibility and large-area producibility are highly promising for applications in organic electronics. However, achieving such photophysical materials is challenging because of difficulties in populating and stabilizing susceptible triplet excited states at room temperature. Herein large-area, flexible, transparent, and long-lived RTP systems prepared by doping rationally selected organic chromophores in a poly(vinyl alcohol) (PVA) matrix were realized through a hydrogen-bonding and coassembly strategy. In particular, the 3,6-diphenyl-9H-carbazole (DPCz)-doped PVA film shows long-lived phosphorescence emission (up to 2044.86 ms) and a remarkable duration of afterglow (over 20 s) under ambient conditions. Meanwhile, the 7H-dibenzo[c,g]carbazole (DBCz)-doped PVA film exhibits high absolute luminance of 158.4 mcd m2 after the ultraviolet excitation source is removed. The RTP results not only from suppressing the nonradiative decay by abundant hydrogen-bonding interactions in the PVA matrix but also from minimizing the energy gap (ΔEST) between the singlet state and the triplet state through the coassembly effect. On account of the outstanding mechanical properties and the afterglow performance of these RTP materials, they were applied in the fabrication of flexible 3D objects with repeatable folding and curling properties. Importantly, the multichannel afterglow light-emitting diode arrays were established under ambient conditions. The present long-lived phosphorescent systems demonstrate a bright opportunity for the production of large-area, flexible, and transparent emitting materials.

20.
Sci Transl Med ; 13(603)2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290057

RESUMO

Inflammatory bowel disease (IBD) affects 0.3% of the global population, yet the etiology remains poorly understood. Anti-inflammation therapy has shown great success, but only 60% of patients with IBD benefit from it, indicating that new targets are needed. Here, we report the discovery of an intrinsic counter regulatory mechanism in colitis pathogenesis that may be targeted for IBD treatment. In response to microbial invasion, resident Vimentin+ stromal cells, connective tissue cells genetically marked by Twist2, are activated during the propagation phase of the disease, but not during initiation and resolution phases, and become a primary source of prostaglandin E2 (PGE2). PGE2 induction requires a nuclear factor κB-independent, TLR4-p38MAPK-Cox2 pathway activation. Ablation of each of the pathway genes, but not Rela or Tgfb1, in Twist2 cells enhanced M1 macrophage polarization and granulocyte/T helper 1 (TH1)/TH17 infiltration and aggravated colitis development. PGE2 administration ameliorated colitis in mouse models with defective PGE2 production but not in animals with normal PGE2 induction. Analysis of clinical samples and public domain data revealed increased expression of Cox2, the rate-limiting enzyme of PGE2 biosynthesis, in inflamed tissues, and especially in colon Vimentin+Twist2+ stromal cells, in about 60% of patients with active Crohn's disease or ulcerative colitis. Moreover, Cox2 protein expression was negatively correlated with disease severity, suggesting an involvement of stromal cells in IBD pathogenesis. Thus, the study uncovers an active immune pathway in colitic inflammation that may be targeted to treat patients with IBD with defects in PGE2 production.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Animais , Colo , Humanos , Imunidade Inata , Camundongos , Células Estromais
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