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1.
Nature ; 609(7929): 1029-1037, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36104562

RESUMO

Advancing the spontaneous bottom-up construction of artificial cells with high organizational complexity and diverse functionality remains an unresolved issue at the interface between living and non-living matter1-4. Here, to address this challenge, we developed a living material assembly process based on the capture and on-site processing of spatially segregated bacterial colonies within individual coacervate microdroplets for the endogenous construction of membrane-bounded, molecularly crowded, and compositionally, structurally and morphologically complex synthetic cells. The bacteriogenic protocells inherit diverse biological components, exhibit multifunctional cytomimetic properties and can be endogenously remodelled to include a spatially partitioned DNA-histone nucleus-like condensate, membranized water vacuoles and a three-dimensional network of F-actin proto-cytoskeletal filaments. The ensemble is biochemically energized by ATP production derived from implanted live Escherichia coli cells to produce a cellular bionic system with amoeba-like external morphology and integrated life-like properties. Our results demonstrate a bacteriogenic strategy for the bottom-up construction of functional protoliving microdevices and provide opportunities for the fabrication of new synthetic cell modules and augmented living/synthetic cell constructs with potential applications in engineered synthetic biology and biotechnology.


Assuntos
Células Artificiais , Escherichia coli , Viabilidade Microbiana , Biologia Sintética , Citoesqueleto de Actina/química , Actinas/química , Trifosfato de Adenosina/metabolismo , Células Artificiais/química , Biotecnologia , Escherichia coli/citologia , Histonas/química , Vacúolos/química , Água/química
2.
Nano Lett ; 24(9): 2831-2838, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38385633

RESUMO

High-entropy borides hold potential as electrocatalysts for water oxidation. However, the synthesis of the tailored nanostructures remains a challenge due to the thermodynamic immiscibility of polymetallic components. Herein, a FeCoCuMnRuB nanobox decorated with a nanosheet array was synthesized for the first time by a "coordination-etch-reduction" method. The FeCoCuMnRuB nanobox has various structural characteristics to express the catalytic performance; meanwhile, it combines the high-entropy effect of multiple components with the electron trap effect induced by electron-deficient B, synergistically regulating its electronic structure. As a result, FeCoCuMnRuB nanobox exhibits enhanced OER activity with a low overpotential (η10 = 233 mV), high TOF value (0.0539 s-1), small Tafel slope (61 mV/dec), and a satisfactory stability for 200 h, outperforming the high-entropy alloy and low-entropy borides. This work develops a high entropy and electron-deficient B-driven strategy for motivating the catalytic performance of water oxidation, which broadens the structural diversity and category of high-entropy materials.

3.
Chaos ; 34(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38829794

RESUMO

The adaptation underlying many realistic processes plays a pivotal role in shaping the collective dynamics of diverse systems. Here, we untangle the generic conditions for synchronization transitions in a system of coupled phase oscillators incorporating the adaptive scheme encoded by the feedback between the coupling and the order parameter via a power-law function with different weights. We mathematically argue that, in the subcritical and supercritical correlation scenarios, there exists no critical adaptive fraction for synchronization transitions converting from the first (second)-order to the second (first)-order. In contrast to the synchronization transitions previously deemed, the explosive and continuous phase transitions take place in the corresponding regions as long as the adaptive fraction is nonzero, respectively. Nevertheless, we uncover that, at the critical correlation, the routes toward synchronization depend crucially on the relative adaptive weights. In particular, we unveil that the emergence of a range of interrelated scaling behaviors of the order parameter near criticality, manifesting the subcritical and supercritical bifurcations, are responsible for various observed phase transitions. Our work, thus, provides profound insights for understanding the dynamical nature of phase transitions, and for better controlling and manipulating synchronization transitions in networked systems with adaptation.

4.
Chaos ; 34(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38341762

RESUMO

Collective ordering behaviors are typical macroscopic manifestations embedded in complex systems and can be ubiquitously observed across various physical backgrounds. Elements in complex systems may self-organize via mutual or external couplings to achieve diverse spatiotemporal coordinations. The order parameter, as a powerful quantity in describing the transition to collective states, may emerge spontaneously from large numbers of degrees of freedom through competitions. In this minireview, we extensively discussed the collective dynamics of complex systems from the viewpoint of order-parameter dynamics. A synergetic theory is adopted as the foundation of order-parameter dynamics, and it focuses on the self-organization and collective behaviors of complex systems. At the onset of macroscopic transitions, slow modes are distinguished from fast modes and act as order parameters, whose evolution can be established in terms of the slaving principle. We explore order-parameter dynamics in both model-based and data-based scenarios. For situations where microscopic dynamics modeling is available, as prototype examples, synchronization of coupled phase oscillators, chimera states, and neuron network dynamics are analytically studied, and the order-parameter dynamics is constructed in terms of reduction procedures such as the Ott-Antonsen ansatz, the Lorentz ansatz, and so on. For complicated systems highly challenging to be well modeled, we proposed the eigen-microstate approach (EMP) to reconstruct the macroscopic order-parameter dynamics, where the spatiotemporal evolution brought by big data can be well decomposed into eigenmodes, and the macroscopic collective behavior can be traced by Bose-Einstein condensation-like transitions and the emergence of dominant eigenmodes. The EMP is successfully applied to some typical examples, such as phase transitions in the Ising model, climate dynamics in earth systems, fluctuation patterns in stock markets, and collective motion in living systems.

5.
Dig Endosc ; 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38433315

RESUMO

OBJECTIVES: This consensus was developed by the Asian EUS Group (AEG), who aimed to formulate a set of practice guidelines addressing various aspects of endoscopic ultrasound-guided tissue acquisition (EUS-TA). METHODS: The AEG initiated the development of consensus statements and formed an expert panel comprising surgeons, gastroenterologists, and pathologists. Three online consensus meetings were conducted to consolidate the statements and votes. The statements were presented and discussed in the first two consensus meetings and revised according to comments. Final voting was conducted at a third consensus meeting. The Grading of Recommendations, Assessment, Development, and Evaluation system was adopted to define the strength of the recommendations and quality of evidence. RESULTS: A total of 20 clinical questions and statements regarding EUS-TA were formulated. The committee recommended that fine-needle biopsy (FNB) needles be preferred over conventional fine-needle aspiration (FNA) needles for EUS-TA of subepithelial lesions. For solid pancreatic masses, rapid on-site evaluation is not routinely recommended when FNB needles are used. For dedicated FNB needles, fork-tip and Franseen-tip needles have essentially equivalent performance. CONCLUSION: This consensus provides guidance for EUS-TA, thereby enhancing the quality of EUS-TA.

6.
Nano Lett ; 23(12): 5859-5867, 2023 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-36971675

RESUMO

The so-called "hard-to-transfect cells" are well-known to present great challenges to intracellular delivery, but detailed understandings of the delivery behaviors are lacking. Recently, we discovered that vesicle trapping is a likely bottleneck of delivery into a type of hard-to-transfect cells, namely, bone-marrow-derived mesenchymal stem cells (BMSCs). Driven by this insight, herein, we screened various vesicle trapping-reducing methods on BMSCs. Most of these methods failed in BMSCs, although they worked well in HeLa cells. In stark contrast, coating nanoparticles with a specific form of poly(disulfide) (called PDS1) nearly completely circumvented vesicle trapping in BMSCs, by direct cell membrane penetration mediated by thiol-disulfide exchange. Further, in BMSCs, PDS1-coated nanoparticles dramatically enhanced the transfection efficiency of plasmids of fluorescent proteins and substantially improved osteoblastic differentiation. In addition, mechanistic studies suggested that higher cholesterol content in plasma membranes of BMSCs might be a molecular-level reason for the greater difficulty of vesicle escape in BMSCs.


Assuntos
Células da Medula Óssea , Desenvolvimento Industrial , Humanos , Células HeLa , Transfecção , Diferenciação Celular , Células Cultivadas
7.
J Am Chem Soc ; 145(27): 14727-14736, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37369121

RESUMO

The self-driven organization of model protocells into higher-order nested cytomimetic systems with coordinated structural and functional relationships offers a step toward the autonomic implementation of artificial multicellularity. Here, we describe an endosymbiotic-like pathway in which proteinosomes are captured within membranized alginate/silk fibroin coacervate vesicles by guest-mediated reconfiguration of the host protocells. We demonstrate that interchange of coacervate vesicle and droplet morphologies through proteinosome-mediated urease/glucose oxidase activity produces discrete nested communities capable of integrated catalytic activity and selective disintegration. The self-driving capacity is modulated by an internalized fuel-driven process using starch hydrolases sequestered within the host coacervate phase, and structural stabilization of the integrated protocell populations can be achieved by on-site enzyme-mediated matrix reinforcement involving dipeptide supramolecular assembly or tyramine-alginate covalent cross-linking. Our work highlights a semi-autonomous mechanism for constructing symbiotic cell-like nested communities and provides opportunities for the development of reconfigurable cytomimetic materials with structural, functional, and organizational complexity.


Assuntos
Células Artificiais , Células Artificiais/química , Urease
8.
J Am Chem Soc ; 145(18): 10396-10403, 2023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-37104061

RESUMO

The design and construction of synthetic protocells capable of stimuli response and homeostatic regulation is an important challenge for synthetic protobiology. Here, we develop a step toward the construction of model protocells capable of a hypotonic stress-induced volume response that facilitates an increase in membrane permeability and the triggering of endogenous enzyme reactions. We describe a facile self-transformation process for constructing single- or multichambered molecularly crowded protocells based on the osmotic reconfiguration of lipid-coated coacervate droplets into multicompartmentalized coacervate vesicles. Hypotonic swelling broadens membrane permeability and increases transmembrane transport such that protease-based hydrolysis and enzyme cascades can be triggered and enhanced within the protocells by osmotically induced expansion. Specifically, we demonstrate how the enhanced production of nitric oxide (NO) within the swollen coacervate vesicles can be used to induce in vitro blood vessel vasodilation in thoracic artery rings. Our approach provides opportunities for designing reconfigurable model protocells capable of homeostatic volume regulation, dynamic structural reorganization, and adaptive functionality in response to changes in environment osmolarity, and could find applications in biomedicine, cellular diagnostics, and bioengineering.


Assuntos
Células Artificiais , Células Artificiais/química , Bioengenharia
9.
Diabet Med ; 40(7): e15031, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36537855

RESUMO

BACKGROUND: Diabetic foot ulcer (DFU) remains a serious chronic diabetic complication that can lead to disability. CircRNA-itchy E3 ubiquitin protein ligase (circ-ITCH) was observed to be down-regulated in diabetic retinopathy and diabetic nephropathy, and overexpression of circ-ITCH could inhibit the processes of these diseases. However, the detailed physiological and pathological functions of circ-ITCH in wound healing of DFU remain undetermined. METHODS: Exosomes derived from bone marrow stromal cells (BMSCs) were isolated and identified. Cell viability and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by cell counting kit-8 (CCK-8) and tube formation assays, respectively. The interplays of circ-ITCH, TATA-Box-binding protein associated factor 15 (TAF15) and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA were analysed by RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) combined immunofluorescent staining and RNA pull-down assays. qRT-PCR, western blot or immunohistochemistry (IHC) were used to measure the expression of circ-ITCH, TAF15, Nrf2, vascular endothelial growth factor (VEGFR) and ferroptosis-related makers. The mice DFU model was established to verify the in vitro results. RESULTS: Circ-ITCH was down-regulated in in vitro and in vivo models of DFU. Deferoxamine (DFO), an iron chelating agent, improved the viability and angiogenic ability of high glucose (HG)-treated HUVECs. Overexpression of circ-ITCH or co-cultured with exosomal circ-ITCH from BMSCs could alleviate HG-induced ferroptosis and improve the angiogenesis ability of HUVECs. Circ-ITCH in HUVECs recruited TAF15 protein to stabilize Nrf2 mRNA, thus activating the Nrf2 signalling pathway and suppressing ferroptosis. Exosomal circ-ITCH from BMSCs also accelerated the wound healing process by inhibiting ferroptosis in the DFU mice in a time-dependent manner. CONCLUSION: Exosomal circ-ITCH from BMSCs inhibited ferroptosis and improved the angiogenesis of HUVECs through activation of the Nrf2 signalling pathway by recruiting TAF15 protein, ultimately accelerating the wound healing process in DFU.


Assuntos
Diabetes Mellitus , Pé Diabético , Ferroptose , Células-Tronco Mesenquimais , Humanos , Camundongos , Animais , Pé Diabético/terapia , Pé Diabético/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Fator A de Crescimento do Endotélio Vascular , Hibridização in Situ Fluorescente , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Cicatrização , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Modelos Animais de Doenças , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , RNA Mensageiro/metabolismo , Diabetes Mellitus/metabolismo
10.
Dig Dis Sci ; 68(5): 1835-1846, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36459293

RESUMO

BACKGROUND/AIMS: Mesenchymal stem cells (MSCs) are a type of adult pluripotent stem cell that has anti-inflammatory and immunomodulatory effects, and whose conditioned medium (CM) has also been found to be effective. We used MSC and CM enemas to investigate their ameliorative effects in a mouse model of colitis. METHODS: We employed MSCs, CM, and MSCs + ML385 (an inhibitor of Nrf2) in dextran sodium sulfate (DSS)-induced colitis. Mice were sacrificed on day 8, and the effects of MSC or CM treatment on the levels of inflammation and oxidative stress in colonic epithelial cells were evaluated by histological analyses. RESULTS: MSCs inhibited inflammatory cell infiltration and proinflammatory cytokine expression in the colon. In addition, MSCs reduced extracellular matrix deposition and maintained the mechanical barrier and permeability of colonic epithelial cells. Mechanistically, MSCs activated Nrf2, which then increased HO-1 and NQO-1 levels and downregulated the expression of Keap1 to suppress reactive oxygen species production and MDA generation, accompanied by increases in components of the enzymatic antioxidant system, including SOD, CAT, GSH-Px, and T-AOC. However, after administering an Nrf2 inhibitor (ML385) to block the Nrf2/Keap1/ARE pathway, we failed to observe protective effects of MSCs in mice with colitis. CM alone also produced some of the therapeutic benefits of MSCs but was not as effective as MSCs. CONCLUSIONS: Our data confirmed that MSCs and CM can effectively improve intestinal mucosal repair in experimental colitis and that MSCs can improve this condition by activating the Nrf2/Keap1/ARE pathway.


Assuntos
Colite , Células-Tronco Mesenquimais , Camundongos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Colite/induzido quimicamente , Colite/terapia , Colite/metabolismo , Transdução de Sinais , Células-Tronco Mesenquimais/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
11.
Curr Microbiol ; 80(4): 113, 2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36823402

RESUMO

A novel Gram-staining negative, aerobic, rod-shaped bacterium, designated strain YIM DDC1T, was isolated from an estuary sediment sample of Dongda River flowing into Dianchi lake in Yunnan, southwest China. The strain displayed growth at 10-40 °C (optimum of 28 °C), pH 5.0-9.0 (optimum of 7.0-8.0) and in presence of 0-3% (w/v) NaCl (optimum of 0-1%). Strain YIM DDC1T comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and two unidentified aminolipids as the predominant polar lipids; the ubiquinone 10 as the major respiratory quinone; and summed feature 8 (C18:1ω6c and/or C18:1ω7c), summed feature 3 (C16:1ω7c and/or C16:1ω6c) and C18:1 2-OH as the major cellular fatty acids. Analysis of 16S rRNA showed that YIM DDC1T represents a member of the genus Azospirillum, and was closely related to A. brasilense ATCC 29145 T (98.9%), A. baldaniorum Sp245T (98.2%), A. argentinense Az39T (98.2%) and A. formosense CC-Nfb-7 T (98.2%). The draft genome size was 7.15 Mbp with a 68.4% G + C content. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain YIM DDC1T and the aforementioned closely related strains exhibited similarity in the range of 93.8-93.5% and 53.7-52.7%, respectively. nif gene cluster (nifHDK) and denitrification genes ((napA, nirS, nirK, norBC and nosZ) detected in the genome indicated its potential nitrogen fixation and full-fledged denitrifying function. Based on combined genotypic and phenotypic data, strain YIM DDC1T represents a novel species of the genus Azospirillum, for which the name Azospirillum aestuarii sp. nov. is proposed. The type strain is YIM DDC1T (= KCTC 42887 T = CGMCC 1.17325 T).


Assuntos
Azospirillum , Fosfolipídeos , Fosfolipídeos/química , Rios/microbiologia , Azospirillum/genética , Estuários , RNA Ribossômico 16S/genética , China , Ácidos Graxos/química , DNA , Filogenia , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA
12.
J Cell Mol Med ; 26(7): 2076-2088, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35152537

RESUMO

Doxorubicin (Dox) is a broad-spectrum antitumour agent; however, its clinical application is impeded due to the cumulative cardiotoxicity. The present study aims to investigate the role and underlying mechanisms of microRNA-495-3p (miR-495-3p) in Dox-induced cardiotoxicity. Herein, we found that cardiac miR-495-3p expression was significantly decreased in Dox-treated hearts, and that the miR-495-3p agomir could prevent oxidative stress, cell apoptosis, cardiac mass loss, fibrosis and cardiac dysfunction upon Dox stimulation. In contrast, the miR-495-3p antagomir dramatically aggravated Dox-induced cardiotoxicity in mice. Besides, we found that the miR-495-3p agomir attenuated, while the miR-495-3p antagomir exacerbated Dox-induced oxidative stress and cellular injury in vitro. Mechanistically, we demonstrated that miR-495-3p directly bound to the 3'-untranslational region of phosphate and tension homology deleted on chromosome ten (PTEN), downregulated PTEN expression and subsequently activated protein kinase B (PKB/AKT) pathway, and that PTEN overexpression or AKT inhibition completely abolished the cardioprotective effects of the miR-495-3p agomir. Our study for the first time identify miR-495-3p as an endogenous protectant against Dox-induced cardiotoxicity through activating AKT pathway in vivo and in vitro.


Assuntos
Cardiotoxicidade , MicroRNAs , Animais , Apoptose/genética , Cardiotoxicidade/patologia , Doxorrubicina/toxicidade , Camundongos , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/metabolismo
13.
J Am Chem Soc ; 144(9): 3855-3862, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35192333

RESUMO

Controlling the dynamics of mixed communities of cell-like entities (protocells) provides a step toward the development of higher-order cytomimetic behaviors in artificial cell consortia. In this paper, we develop a caged protocell model with a molecularly crowded coacervate interior surrounded by a non-cross-linked gold (Au)/poly(ethylene glycol) (PEG) nanoparticle-jammed stimuli-responsive membrane. The jammed membrane is unlocked by either exogenous light-mediated Au/PEG dissociation at the Au surface or endogenous enzyme-mediated cleavage of a ketal linkage on the PEG backbone. The membrane assembly/disassembly process is used for the controlled and selective uptake of guest protocells into the caged coacervate microdroplets as a path toward an all-water model of triggerable transmembrane uptake in synthetic protocell communities. Active capture of the guest protocells stems from the high sequestration potential of the coacervate interior such that tailoring the surface properties of the guest protocells provides a rudimentary system of protocell sorting. Our results highlight the potential for programming surface-contact interactions between artificial membrane-bounded compartments and could have implications for the development of protocell networks, storage and delivery microsystems, and microreactor technologies.


Assuntos
Células Artificiais , Nanopartículas , Células Artificiais/metabolismo
14.
J Transl Med ; 20(1): 337, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902881

RESUMO

BACKGROUND: Asprosin, a newly discovered adipokine, is a C-terminal cleavage product of profibrillin. Asprosin has been reported to participate in lipid metabolism and cardiovascular disease, but its role in atherogenesis remains elusive. METHODS: Asprosin was overexpressed in THP-1 macrophage-derived foam cells and apoE-/- mice using the lentiviral vector. The expression of relevant molecules was determined by qRT-PCR and/or western blot. The intracellular lipid accumulation was evaluated by high-performance liquid chromatography and Oil red O staining. HE and Oil red O staining was employed to assess plaque burden in vivo. Reverse cholesterol transport (RCT) efficiency was measured using [3H]-labeled cholesterol. RESULTS: Exposure of THP-1 macrophages to oxidized low-density lipoprotein down-regulated asprosin expression. Lentivirus-mediated overexpression of asprosin promoted cholesterol efflux and inhibited lipid accumulation in THP-1 macrophage-derived foam cells. Mechanistic analysis revealed that asprosin overexpression activated p38 and stimulated the phosphorylation of ETS-like transcription factor (Elk-1) at Ser383, leading to Elk-1 nuclear translocation and the transcriptional activation of ATP binding cassette transporters A1 (ABCA1) and ABCG1. Injection of lentiviral vector expressing asprosin diminished atherosclerotic lesion area, increased plaque stability, improved plasma lipid profiles and facilitated RCT in apoE-/- mice. Asprosin overexpression also increased the phosphorylation of p38 and Elk-1 as well as up-regulated the expression of ABCA1 and ABCG1 in the aortas. CONCLUSION: Asprosin inhibits lipid accumulation in macrophages and decreases atherosclerotic burden in apoE-/- mice by up-regulating ABCA1 and ABCG1 expression via activation of the p38/Elk-1 signaling pathway.


Assuntos
Aterosclerose , Placa Aterosclerótica , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Apolipoproteínas E/metabolismo , Aterosclerose/patologia , Colesterol/metabolismo , Macrófagos/metabolismo , Camundongos , Placa Aterosclerótica/patologia
15.
Cytokine ; 155: 155912, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35598525

RESUMO

Both inflammatory response and oxidative stress are regarded as two critical contributors to atherosclerosis. Kcnq1 overlapping transcript 1 (KCNQ1OT1) is an imprinted antisense long non-coding RNA in the kcnq1 locus. Our previous study has demonstrated that KCNQ1OT1 aggravates atherosclerosis by promoting macrophage lipid accumulation. However, its role in atherogenesis remains to be elucidated. This study aimed to observe the impact of KCNQ1OT1 on oxidized low-density lipoprotein (ox-LDL)-induced inflammatory response and oxidative stress and to explore the underlying mechanism. We found that ox-LDL up-regulated KCNQ1OT1 expression in THP-1 macrophages. Knockdown of KCNQ1OT1 increased miR-137 levels, decreased tumor necrosis factor-α-induced protein 1 (TNFAIP1) expression, and inhibited inflammatory response and alleviated oxidative stress in ox-LDL-treated THP-1 macrophages. A ceRNA regulatory network was identified among KCNQ1OT1, miR-137 and TNFAIP1. The inhibitory effect of KCNQ1OT1 knockdown on inflammatory response and oxidative stress was significantly reversed by miR-137 prevention or TNFAIP1 overexpression. In summary, these findings suggest that silencing of KCNQ1OT1 suppresses inflammatory response and oxidative stress induced by ox-LDL through the miR-137/TNFAIP1 pathway in THP-1 macrophages, thereby providing novel mechanistical insights into its pro-atherosclerotic action.


Assuntos
Aterosclerose , MicroRNAs , RNA Longo não Codificante , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose , Aterosclerose/metabolismo , Humanos , Canal de Potássio KCNQ1/metabolismo , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Estresse Oxidativo/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Células THP-1 , Fator de Necrose Tumoral alfa/metabolismo
16.
Stat Med ; 41(4): 665-680, 2022 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-34773277

RESUMO

The medium-throughput mRNA abundance platform NanoString nCounter has gained great popularity in the past decade, due to its high sensitivity and technical reproducibility as well as remarkable applicability to ubiquitous formalin fixed paraffin embedded (FFPE) tissue samples. Based on RCRnorm developed for normalizing NanoString nCounter data and Bayesian LASSO for variable selection, we propose a fully integrated Bayesian method, called RCRdiff, to detect differentially expressed (DE) genes between different groups of tissue samples (eg, normal and cancer). Unlike existing methods that often require normalization performed beforehand, RCRdiff directly handles raw read counts and jointly models the behaviors of different types of internal controls along with DE and non-DE gene patterns. Doing so would avoid efficiency loss caused by ignoring estimation uncertainty from the normalization step in a sequential approach and thus can offer more reliable statistical inference. We also propose clustering-based strategies for DE gene selection, which do not require any external dataset and are free of any arbitrary cutoff. Empirical evidence of the attractiveness of RCRdiff is demonstrated via extensive simulation and data examples.


Assuntos
Perfilação da Expressão Gênica , Teorema de Bayes , Perfilação da Expressão Gênica/métodos , Humanos , Reprodutibilidade dos Testes
17.
BMC Musculoskelet Disord ; 23(1): 751, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35927661

RESUMO

BACKGROUND: Lateral column lengthening calcaneal osteotomy is a powerful procedure for correcting forefoot abduction in flatfoot deformity. However, it involves the risk of damaging articular facets of the subtalar joint. The optimal method to avoid violating the subtalar joint during lateral column lengthening remained controversial in published reports, implying that the subtalar joint might present anatomical variations among different nationalities. Therefore, the objective of this study was to perform an anatomical study by targeting the healthy Chinese population for the purpose of identifying the optimal procedure for lateral column lengthening calcaneal osteotomy according to anatomical patterns of the subtalar joint. METHODS: A total of 72 ft from 70 fresh frozen cadavers were obtained from the Department of Anatomy of Central South University. For each foot, soft tissues were surgically removed from the bones, and the calcaneus was completely separated from other bones to recognize the anatomical features of the calcaneus. The distance between the calcaneocuboid joint and the articular facet of the subtalar joint was measured by digital calipers for further analysis. RESULTS: Out of the 72 ft, 36.1% had separated anterior and middle facets in the calcaneus, and 63.8% had partly or completely fused anterior and middle facets. In the calcanei with discrete facets, the mean distance from the calcaneocuboid joint to the proximal margin of the anterior facet was 12.75 ± 2.10 mm, and the mean width of the separation between the anterior and middle facets was 2.43 ± 1.41 mm. In the calcanei with partly or completely fused anterior and middle facets, the mean width of the narrowest part of the tarsal sinus was 5.81 ± 0.62 mm and 6.25 ± 0.35 mm, respectively. CONCLUSIONS: The anatomy of the subtalar joint presents significant individual variations in the Chinese population. Calcanei with partly or completely fused anterior and middle facets were observed in nearly two thirds of individuals. Since the modified Evans procedure might potentially incur damage to the subtalar joint facets, the Hintermann procedure or other modified extra-articular lateral column lengthening procedures may be more applicable to the Chinese population.


Assuntos
Calcâneo , Pé Chato , Articulação Talocalcânea , Calcâneo/cirurgia , China , Pé Chato/diagnóstico por imagem , Pé Chato/cirurgia , Humanos , Osteotomia/métodos , Articulação Talocalcânea/cirurgia
18.
Chaos ; 32(5): 053120, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35649978

RESUMO

We study synchronization in large populations of coupled phase oscillators with time delays and higher-order interactions. With each of these effects individually giving rise to bistability between incoherence and synchronization via subcriticality at the onset of synchronization and the development of a saddle node, we find that their combination yields another mechanism behind bistability, where supercriticality at onset may be maintained; instead, the formation of two saddle nodes creates tiered synchronization, i.e., bistability between a weakly synchronized state and a strongly synchronized state. We demonstrate these findings by first deriving the low dimensional dynamics of the system and examining the system bifurcations using a stability and steady-state analysis.

19.
Chaos ; 32(6): 063106, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35778151

RESUMO

We consider a variant of the mean-field model of coupled phase oscillators with uniform distribution of natural frequencies. By establishing correlations between the quenched disorder of intrinsic frequencies and coupling strength with both in- and out-coupling heterogeneities, we reveal a generic criterion for the onset of partial locking that takes place in a domain with the coexistence of phase-locked oscillators and drifters. The critical points manifesting the instability of the stationary states are obtained analytically. In particular, the bifurcation mechanism of the equilibrium states is uncovered by the use of frequency-dependent version of the Ott-Antonsen reduction consistently with the analysis based on the self-consistent approach. We demonstrate that both the manner of coupling heterogeneity and correlation exponent have influence on the emergent patterns of partial locking. Our research could find applicability in better understanding the phase transitions and related collective phenomena involving synchronization control in networked systems.

20.
Foot Ankle Surg ; 28(8): 1452-1457, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36041988

RESUMO

BACKGROUND: It remains unclear whether to perform a bone graft is necessary during posterior arthroscopic subtalar arthrodesis. The present research aimed to comparatively analyze the outcomes of arthroscopic subtalar arthrodesis through a 3-portal posterior approach with or without bone graft. METHODS: A total of 93 patients with subtalar arthritis who underwent posterior arthroscopic subtalar arthrodesis were retrospectively examined. The patients were divided into two groups according to whether they received bone graft or not. The clinical outcomes were compared for analysis. RESULTS: Among the 93 patients included, 53 received bone graft and 40 did not. The union rate and time to osseous fusion suggested no significant difference between the two groups. The improvement of clinical outcomes were comparable between the two groups at the final follow-up. CONCLUSIONS: In the present study, bone graft could not effectively reduce the risk of nonunion and improve the outcome.


Assuntos
Artrite , Articulação Talocalcânea , Humanos , Articulação Talocalcânea/cirurgia , Estudos Retrospectivos , Artrodese , Artrite/cirurgia , Transplante Ósseo , Resultado do Tratamento
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