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1.
Nat Immunol ; 16(11): 1142-52, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26414765

RESUMO

Mitochondria need to be juxtaposed to phagosomes for the synergistic production of ample reactive oxygen species (ROS) in phagocytes to kill pathogens. However, how phagosomes transmit signals to recruit mitochondria has remained unclear. Here we found that the kinases Mst1 and Mst2 functioned to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activated the GTPase Rac to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for the recruitment of mitochondria to phagosomes. Inactive forms of Rac, including the human Rac2(D57N) mutant, disrupted the TRAF6-ECSIT complex by sequestering TRAF6 and substantially diminished ROS production and enhanced susceptibility to bacterial infection. Our findings demonstrate that the TLR-Mst1-Mst2-Rac signaling axis is critical for effective phagosome-mitochondrion function and bactericidal activity.


Assuntos
Fagócitos/imunologia , Fagócitos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Infecções Bacterianas/etiologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/metabolismo , Atividade Bactericida do Sangue/imunologia , Linhagem Celular , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Antígenos de Histocompatibilidade Menor , Mitocôndrias/imunologia , Mitocôndrias/metabolismo , Mitocôndrias/microbiologia , Fagócitos/microbiologia , Fagossomos/imunologia , Fagossomos/metabolismo , Fagossomos/microbiologia , Proteína Quinase C-alfa/metabolismo , Proteínas Serina-Treonina Quinases/deficiência , Proteínas Serina-Treonina Quinases/genética , Sepse/etiologia , Sepse/imunologia , Sepse/metabolismo , Serina-Treonina Quinase 3 , Transdução de Sinais , Fator 6 Associado a Receptor de TNF , Receptores Toll-Like/metabolismo , Ubiquitinação , Proteínas rac de Ligação ao GTP/genética , Proteínas rac de Ligação ao GTP/metabolismo , Inibidor beta de Dissociação do Nucleotídeo Guanina rho/metabolismo
2.
J Immunol ; 212(3): 397-409, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38088801

RESUMO

SHP-1 (Src homology region 2 domain-containing phosphatase 1) is a well-known negative regulator of T cells, whereas its close homolog SHP-2 is the long-recognized main signaling mediator of the PD-1 inhibitory pathway. However, recent studies have challenged the requirement of SHP-2 in PD-1 signaling, and follow-up studies further questioned the alternative idea that SHP-1 may replace SHP-2 in its absence. In this study, we systematically investigate the role of SHP-1 alone or jointly with SHP-2 in CD8+ T cells in a series of gene knockout mice. We show that although SHP-1 negatively regulates CD8+ T cell effector function during acute lymphocytic choriomeningitis virus (LCMV) infection, it is dispensable for CD8+ T cell exhaustion during chronic LCMV infection. Moreover, in contrast to the mortality of PD-1 knockout mice upon chronic LCMV infection, mice double deficient for SHP-1 and SHP-2 in CD8+ T cells survived without immunopathology. Importantly, CD8+ T cells lacking both phosphatases still differentiate into exhausted cells and respond to PD-1 blockade. Finally, we found that SHP-1 and SHP-2 suppressed effector CD8+ T cell expansion at the early and late stages, respectively, during chronic LCMV infection.


Assuntos
Coriomeningite Linfocítica , Vírus da Coriomeningite Linfocítica , Animais , Camundongos , Linfócitos T CD8-Positivos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor de Morte Celular Programada 1/metabolismo , Exaustão das Células T
3.
EMBO Rep ; 24(1): e54935, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36314725

RESUMO

The centrosome, a non-membranous organelle, constrains various soluble molecules locally to execute its functions. As the centrosome is surrounded by various dense components, we hypothesized that it may be bordered by a putative diffusion barrier. After quantitatively measuring the trapping kinetics of soluble proteins of varying size at centrosomes by a chemically inducible diffusion trapping assay, we find that centrosomes are highly accessible to soluble molecules with a Stokes radius of less than 5.8 nm, whereas larger molecules rarely reach centrosomes, indicating the existence of a size-dependent diffusion barrier at centrosomes. The permeability of this barrier is tightly regulated by branched actin filaments outside of centrosomes and it decreases during anaphase when branched actin temporally increases. The actin-based diffusion barrier gates microtubule nucleation by interfering with γ-tubulin ring complex recruitment. We propose that actin filaments spatiotemporally constrain protein complexes at centrosomes in a size-dependent manner.


Assuntos
Microtúbulos , Tubulina (Proteína) , Tubulina (Proteína)/metabolismo , Microtúbulos/metabolismo , Actinas/metabolismo , Centrossomo/metabolismo , Citoesqueleto de Actina/metabolismo
4.
J Mol Cell Cardiol ; 190: 62-75, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38583797

RESUMO

Intimal hyperplasia is a complicated pathophysiological phenomenon attributable to in-stent restenosis, and the underlying mechanism remains unclear. Interleukin enhancer-binding factor 3 (ILF3), a double-stranded RNA-binding protein involved in regulating mRNA stability, has been recently demonstrated to assume a crucial role in cardiovascular disease; nevertheless, its impact on intimal hyperplasia remains unknown. In current study, we used samples of human restenotic arteries and rodent models of intimal hyperplasia, we found that vascular smooth muscle cell (VSMC) ILF3 expression was markedly elevated in human restenotic arteries and murine ligated carotid arteries. SMC-specific ILF3 knockout mice significantly suppressed injury induced neointimal formation. In vitro, platelet-derived growth factor type BB (PDGF-BB) treatment elevated the level of VSMC ILF3 in a dose- and time-dependent manner. ILF3 silencing markedly inhibited PDGF-BB-induced phenotype switching, proliferation, and migration in VSMCs. Transcriptome sequencing and RNA immunoprecipitation sequencing depicted that ILF3 maintained its stability upon binding to the mRNA of the high-mobility group box 1 protein (HMGB1), thereby exerting an inhibitory effect on the transcription of dual specificity phosphatase 16 (DUSP16) through enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3). Therefore, the results both in vitro and in vivo indicated that the loss of ILF3 in VSMC ameliorated neointimal hyperplasia by regulating the STAT3/DUSP16 axis through the degradation of HMGB1 mRNA. Our findings revealed that vascular injury activates VSMC ILF3, which in turn promotes intima formation. Consequently, targeting specific VSMC ILF3 may present a potential therapeutic strategy for ameliorating cardiovascular restenosis.


Assuntos
Proteína HMGB1 , Hiperplasia , Camundongos Knockout , Músculo Liso Vascular , Miócitos de Músculo Liso , Proteínas do Fator Nuclear 90 , Estabilidade de RNA , Fator de Transcrição STAT3 , Túnica Íntima , Animais , Humanos , Masculino , Camundongos , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Regulação da Expressão Gênica , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Neointima/metabolismo , Neointima/patologia , Proteínas do Fator Nuclear 90/metabolismo , Proteínas do Fator Nuclear 90/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Túnica Íntima/metabolismo , Túnica Íntima/patologia
5.
J Am Chem Soc ; 146(5): 3553-3563, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38285529

RESUMO

Flexible membranes with ultrathin thickness and excellent mechanical properties have shown great potential for broad uses in solid polymer electrolytes (SPEs), on-skin electronics, etc. However, an ultrathin membrane (<5 µm) is rarely reported in the above applications due to the inherent trade-off between thickness and antifailure ability. We discover a protic solvent penetration strategy to prepare ultrathin, ultrastrong layered films through a continuous interweaving of aramid nanofibers (ANFs) with the assistance of simultaneous protonation and penetration of a protic solvent. The thickness of a pure ANF film can be controlled below 5 µm, with a tensile strength of 556.6 MPa, allowing us to produce the thinnest SPE (3.4 µm). The resultant SPEs enable Li-S batteries to cycle over a thousand times at a high rate of 1C due to the small ionic impedance conferred by the ultrathin characteristic and regulated ionic transportation. Besides, a high loading of the sulfur cathode (4 mg cm-2) with good sulfur utilization was achieved at a mild temperature (35 °C), which is difficult to realize in previously reported solid-state Li-S batteries. Through a simple laminating process at the wet state, the thicker film (tens of micrometers) obtained exhibits mechanical properties comparable to those of thin films and possesses the capability to withstand high-velocity projectile impacts, indicating that our technique features a high degree of thickness controllability. We believe that it can serve as a valuable tool to assemble nanomaterials into ultrathin, ultrastrong membranes for various applications.

6.
Clin Immunol ; 263: 110232, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701960

RESUMO

IgA nephropathy (IgAN), which has been confirmed as a complement mediated autoimmune disease, is also one form of glomerulonephritis associated with COVID-19. Here, we aim to investigate the clinical and immunological characteristics of patients with IgAN after COVID-19. The level of plasma level of C5a (p < 0.001), soluble C5b-9 (p = 0.018), FHR5 (p < 0.001) were all significantly higher in Group CoV (33 patients with renal biopsy-proven IgAN experienced COVID-19) compared with Group non-CoV (44 patients with IgAN without COVID-19), respectively. Compared with Group non-CoV, the intensity of glomerular C4d (p = 0.017) and MAC deposition (p < 0.001) and Gd-IgA1 deposition (p = 0.005) were much stronger in Group CoV. Our finding revealed that for IgAN after COVID-19, mucosal immune responses to SARS-CoV-2 infection may result in the overactivation of systemic and renal local complement system, and increased glomerular deposition of Gd-IgA1, which may lead to renal dysfunction and promote renal progression in IgAN patients.


Assuntos
COVID-19 , Glomerulonefrite por IGA , SARS-CoV-2 , Humanos , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/sangue , COVID-19/imunologia , COVID-19/complicações , Feminino , Masculino , Adulto , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Ativação do Complemento/imunologia , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Glomérulos Renais/patologia , Glomérulos Renais/imunologia , Complemento C5a/imunologia , Complemento C5a/metabolismo
7.
Opt Express ; 32(8): 14090-14101, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859364

RESUMO

We propose what we believe to be a novel direct detection phase-sensitive optical time-domain reflectometry (Φ-OTDR) based on ultra-weak fiber Bragg grating (UWFBG) array to achieve distributed vibration measurements with exceptional sensitivity and remarkable stability. Our system employs a pulse modulator to generate a double pulse and achieves linear phase modulation of one pulse by one cycle through a phase modulator. The phase change can be quantitatively demodulated using our proposed N-step phase-shifted demodulation algorithm. This method effectively mitigates the influence of phase noise of the laser and the pulse modulator, while also eliminating fluctuations in the half-voltage of the phase modulator. Compared with the existing phase modulation methods, our method avoids stringent requirements for the stability and precision of phase modulation. Moreover, we propose a phase-shifted approximation method, breaking the limitation of sensing length on the traditional differential approximation method and improving the accuracy significantly. The technique's effectiveness is experimentally demonstrated on a 1 km UWFBG array with a reflectivity of -40 dB to -45 dB and a spatial resolution of 10 m. Vibrations with different amplitudes are measured quantitatively with good linearity. The low-frequency self-noise is greatly suppressed and the overall self-noise is -54.3 dB rad2/Hz.

8.
Biomacromolecules ; 25(4): 2438-2448, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38502912

RESUMO

The treatment of infected wounds faces substantial challenges due to the high incidence and serious infection-related complications. Natural-based hydrogel dressings with favorable antibacterial properties and strong applicability are urgently needed. Herein, we developed a composite hydrogel by constructing multiple networks and loading ciprofloxacin for infected wound healing. The hydrogel was synthesized via a Schiff base reaction between carboxymethyl chitosan and oxidized sodium alginate, followed by the polymerization of the acrylamide monomer. The resultant hydrogel dressing possessed a good self-healing ability, considerable compression strength, and reliable compression fatigue resistance. In vitro assessment showed that the composite hydrogel effectively eliminated bacteria and exhibited an excellent biocompatibility. In a model of Staphylococcus aureus-infected full-thickness wounds, wound healing was significantly accelerated without scars through the composite hydrogel by reducing wound inflammation. Overall, this study opens up a new way for developing multifunctional hydrogel wound dressings to treat wound infections.


Assuntos
Quitosana , Hidrogéis , Hidrogéis/farmacologia , Cicatrização , Antibacterianos/farmacologia , Ciprofloxacina , Bandagens
9.
Inorg Chem ; 63(19): 8925-8937, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38683480

RESUMO

The development of efficient urea oxidation reaction (UOR) catalysts helps UOR replace the oxygen evolution reaction (OER) in hydrogen production from water electrolysis. Here, we prepared Fe-doped Ni2P/NiSe2 composite catalyst (Fe-Ni2P/NiSe2-12) by using phosphating-selenizating and acid etching to increase the intrinsic activity and active areas. Spectral characterization and theoretical calculations demonstrated that electrons flowed through the Ni-P-Fe-interface-Ni-Se-Fe, thus conferring high UOR activity to Fe-Ni2P/NiSe2-12, which only needed 1.39 V vs RHE to produce the current density of 100 mA cm-2. Remarkably, this potential was 164 mV lower than that required for the OER under the same conditions. Furthermore, EIS demonstrated that UOR driven by the Fe-Ni2P/NiSe2-12 exhibited faster interfacial reactions, charge transfer, and current response compared to OER. Consequently, the Fe-Ni2P/NiSe2-12 catalyst can effectively prevent competition with OER and NSOR, making it suitable for efficient hydrogen production in UOR-assisted water electrolysis. Notably, when water electrolysis is operated at a current density of 40 mA cm-2, this UOR-assisted system can achieve a decrease of 140 mV in the potential compared to traditional water electrolysis. This study presents a novel strategy for UOR-assisted water splitting for energy-saving hydrogen production.

10.
Inorg Chem ; 63(8): 3702-3711, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38335057

RESUMO

A long-term goal of rechargeable zinc-air batteries (ZABs) has always been to design bifunctional electrocatalysts that are robust, effective, and affordable for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). It has become a feasible method to construct metal/metal oxide interfaces to achieve superior electrocatalytic performance for ORR and OER by enhanced charge transfer. In this study, Co/Co3O4 heterojunctions were successfully prepared and encased in porous N-doped mesoporous carbon (Co/Co3O4@NC) via a simple condensation-carbonization-etching method. The extensive specific surface area of Co/Co3O4@NC facilitates effective interaction between the electrolyte and the catalyst, thereby enabling sufficient exposure of active sites for the ORR and the OER, consequently enhancing the rate of transport of active species. The well-designed Co/Co3O4@NC delivers superior ORR catalytic activity with a half-wave potential of 0.82 V (vs RHE) and a low overpotential of 347 mV at 10 mA cm-2 for OER in alkaline solution. The power density of Co/Co3O4@NC-based alkaline aqueous ZAB (156.5 mW cm-2) is superior to the commercial Pt/C + IrO2-based alkaline aqueous ZAB, and the cycling stability of ZAB is up to 220 h. In addition, Co/Co3O4@NC-based ZAB shows a high power density (50.1 mW cm-2). The construction of metal/metal oxide heterojunction encased in N-doped mesoporous carbon provides a novel route for the design of bifunctional electrocatalysts for high-performance ZABs.

11.
Arch Insect Biochem Physiol ; 115(4): e22113, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628056

RESUMO

The efficiency of RNA interference (RNAi) has always limited the research on the phenotype innovation of Lepidoptera insects. Previous studies have found that double-stranded RNA-degrading enzyme (dsRNase) is an important factor in RNAi efficiency, but there have been no relevant reports in butterflies (Papilionoidea). Papilio xuthus is one of the important models in butterflies with an extensive experimental application value. To explore the effect of dsRNase in the RNAi efficiency on butterflies, six dsRNase genes (PxdsRNase 1-6) were identified in P. xuthus genome, and their dsRNA-degrading activities were subsequently detected by ex vivo assays. The result shows that the dsRNA-degrading ability of gut content (<1 h) was higher than hemolymph content (>12 h). We then investigated the expression patterns of these PxdsRNase genes during different tissues and developmental stages, and related RNAi experiments were carried out. Our results show that different PxdsRNase genes had different expression levels at different developmental stages and tissues. The expression of PxdsRNase2, PxdsRNase3, and PxdsRNase6 were upregulated significantly through dsGFP injection, and PxdsRNase genes can be silenced effectively by injecting their corresponding dsRNA. RNAi-of-RNAi studies with PxEbony, which acts as a reporter gene, observed that silencing PxdsRNase genes can increase RNAi efficiency significantly. These results confirm that silencing dsRNase genes can improve RNAi efficiency in P. xuthus significantly, providing a reference for the functional study of insects such as butterflies with low RNAi efficiency.


Assuntos
Borboletas , Animais , Borboletas/genética , Interferência de RNA , RNA de Cadeia Dupla , Insetos/genética , Inativação Gênica
12.
J Comput Assist Tomogr ; 48(4): 640-646, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38346810

RESUMO

OBJECTIVE: This study aimed to investigate whether virtual monoenergetic images (VMIs) can aid radiologists and surgeons in better identifying the arc of Riolan (AOR) and to determine the optimal kilo electron volt (keV) level. METHODS: Thirty-three patients were included. Conventional images (CIs) and VMI (40-100 keV) were reconstructed using arterial phase spectral-based images. The computed tomography (CT) attenuation and noise of the AOR, the CT attenuation of the erector spinal muscle, and the background noise on VMI and CI were measured, respectively. The signal-to-noise ratio, contrast-to-noise ratio (CNR), and signal intensity ratio were calculated. The image quality of the AOR was evaluated according to a 4-point Likert grade. RESULTS: The CT attenuation, noise, CNR, and signal intensity ratio of the AOR were significantly higher in VMI at 40 and 50 keV compared with CI ( P < 0.001); VMI at 40 keV was significantly higher than 50 keV ( P < 0.05). No significant difference in signal-to-noise ratio, background noise, and CT attenuation of the spinal erector muscle was observed between VMI and CI ( P > 0.05). virtual monoenergetic image at 40 keV produced the best subjective scores. CONCLUSIONS: Virtual monoenergetic image at 40 keV makes it easier to observe the AOR with optimized subjective and objective image quality. This may prompt radiologists and surgeons to actively search for it and encourage surgeons to preserve it during splenic flexure takedown.


Assuntos
Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Tomografia Computadorizada por Raios X/métodos , Idoso , Razão Sinal-Ruído , Baço/diagnóstico por imagem , Estudos Retrospectivos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso de 80 Anos ou mais
13.
BMC Med Imaging ; 24(1): 117, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773416

RESUMO

BACKGROUND: Coronary inflammation induces changes in pericoronary adipose tissue (PCAT) can be detected by coronary computed tomography angiography (CCTA). Our aim was to investigate whether different PCAT radiomics model based on CCTA could improve the prediction of major adverse cardiovascular events (MACE) within 3 years. METHODS: This retrospective study included 141 consecutive patients with MACE and matched to patients with non-MACE (n = 141). Patients were randomly assigned into training and test datasets at a ratio of 8:2. After the robust radiomics features were selected by using the Spearman correlation analysis and the least absolute shrinkage and selection operator, radiomics models were built based on different machine learning algorithms. The clinical model was then calculated according to independent clinical risk factors. Finally, an overall model was established using the radiomics features and the clinical factors. Performance of the models was evaluated for discrimination degree, calibration degree, and clinical usefulness. RESULTS: The diagnostic performance of the PCAT model was superior to that of the RCA-model, LAD-model, and LCX-model alone, with AUCs of 0.723, 0.675, 0.664, and 0.623, respectively. The overall model showed superior diagnostic performance than that of the PCAT-model and Cli-model, with AUCs of 0.797, 0.723, and 0.706, respectively. Calibration curve showed good fitness of the overall model, and decision curve analyze demonstrated that the model provides greater clinical benefit. CONCLUSION: The CCTA-based PCAT radiomics features of three major coronary arteries have the potential to be used as a predictor for MACE. The overall model incorporating the radiomics features and clinical factors offered significantly higher discrimination ability for MACE than using radiomics or clinical factors alone.


Assuntos
Tecido Adiposo , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Humanos , Angiografia por Tomografia Computadorizada/métodos , Masculino , Feminino , Tecido Adiposo/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos de Casos e Controles , Angiografia Coronária/métodos , Aprendizado de Máquina , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Tecido Adiposo Epicárdico , Radiômica
14.
PLoS Genet ; 17(11): e1009854, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34723967

RESUMO

The forkhead box (Fox) family of transcription factors are highly conserved and play essential roles in a wide range of cellular and developmental processes. We report an individual with severe neurological symptoms including postnatal microcephaly, progressive brain atrophy and global developmental delay associated with a de novo missense variant (M280L) in the FOXR1 gene. At the protein level, M280L impaired FOXR1 expression and induced a nuclear aggregate phenotype due to protein misfolding and proteolysis. RNAseq and pathway analysis showed that FOXR1 acts as a transcriptional activator and repressor with central roles in heat shock response, chaperone cofactor-dependent protein refolding and cellular response to stress pathways. Indeed, FOXR1 expression is increased in response to cellular stress, a process in which it directly controls HSPA6, HSPA1A and DHRS2 transcripts. The M280L mutant compromises FOXR1's ability to respond to stress, in part due to impaired regulation of downstream target genes that are involved in the stress response pathway. Quantitative PCR of mouse embryo tissues show Foxr1 expression in the embryonic brain. Using CRISPR/Cas9 gene editing, we found that deletion of mouse Foxr1 leads to a severe survival deficit while surviving newborn Foxr1 knockout mice have reduced body weight. Further examination of newborn Foxr1 knockout brains revealed a decrease in cortical thickness and enlarged ventricles compared to littermate wild-type mice, suggesting that loss of Foxr1 leads to atypical brain development. Combined, these results suggest FOXR1 plays a role in cellular stress response pathways and is necessary for normal brain development.


Assuntos
Encéfalo/crescimento & desenvolvimento , Fatores de Transcrição Forkhead/fisiologia , Estresse Fisiológico , Animais , Feminino , Fatores de Transcrição Forkhead/genética , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Knockout , Mutação de Sentido Incorreto , Fenótipo
15.
J Am Chem Soc ; 145(44): 24260-24271, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37886822

RESUMO

Lithium metal batteries (LMBs) coupled with a high-voltage Ni-rich cathode are promising for meeting the increasing demand for high energy density. However, aggressive electrode chemistry imposes ultimate requirements on the electrolytes used. Among the various optimized electrolytes investigated, localized high-concentration electrolytes (LHCEs) have excellent reversibility against a lithium metal anode. However, because they consist of thermally and electrochemically unstable solvents, they have inferior stability at elevated temperatures and high cutoff voltages. Here we report a semisolvated sole-solvent electrolyte to construct a typical LHCE solvation structure but with significantly improved stability using one bifunctional solvent. The designed electrolyte exhibits exceptional stability against both electrodes with suppressed lithium dendrite growth, phase transition, microcracking, and transition metal dissolution. A Li||Ni0.8Co0.1Mn0.1O2 cell with this electrolyte operates stably over a wide temperature range from -20 to 60 °C and has a high capacity retention of 95.6% after the 100th cycle at 4.7 V, and ∼80% of the initial capacity is retained even after 180 cycles. This new electrolyte indicates a new path toward future electrolyte engineering and safe high-voltage LMBs.

16.
J Am Chem Soc ; 145(51): 28224-28232, 2023 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-38108623

RESUMO

By recombining natural cell signaling systems and further reprogramming cell functions, use of genetically engineered cells and bacteria as therapies is an innovative emerging concept. However, the inherent properties and structures of the natural signal sensing and response pathways constrain further development. We present a universal DNA-based sensing toolbox on the cell surface to endow new signal sensing abilities for cells, control cell states, and reprogram multiple cell functions. The sensing toolbox contains a triangular-prismatic-shaped DNA origami framework and a sensing core anchored inside the internal confined space to enhance the specificity and efficacy of the toolbox. As a proof of principle, the sensing toolbox uses the customizable sensing core with signal sensing switches and converters to recognize unconventional signal inputs, deliver functional components to cells, and then control cell responses, including specific tumor cell death, immune cell disinhibition and adhesion, and bacterial expression. This work expands the diversity of cell sensing signals and reprograms biological functions by constructing nanomechanical-natural hybrid cells, providing new strategies for engineering cells and bacteria in diagnosis and treatment applications.


Assuntos
DNA , Transdução de Sinais , Engenharia Genética , Bactérias/genética , Percepção de Quorum
17.
Apoptosis ; 28(11-12): 1646-1665, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37702860

RESUMO

Macrophages represent the first lines of innate defense against pathogenic infections and are poised to undergo multiple forms of regulated cell death (RCD) upon infections or toxic stimuli, leading to multiple organ injury. Triptolide, an active compound isolated from Tripterygium wilfordii Hook F., possesses various pharmacological activities including anti-tumor and anti-inflammatory effects, but its applications have been hampered by toxic adverse effects. It remains unknown whether and how triptolide induces different forms of RCD in macrophages. In this study, we showed that triptolide exhibited significant cytotoxicity on cultured macrophages in vitro, which was associated with multiple forms of lytic cell death that could not be fully suppressed by any one specific inhibitor for a single form of RCD. Consistently, triptolide induced the simultaneous activation of pyroptotic, apoptotic and necroptotic hallmarks, which was accompanied by the co-localization of ASC specks respectively with RIPK3 or caspase-8 as well as their interaction with each other, indicating the formation of PANoptosome and thus the induction of PANoptosis. Triptolide-induced PANoptosis was associated with mitochondrial dysfunction and ROS production. PANoptosis was also induced by triptolide in mouse peritoneal macrophages in vivo. Furthermore, triptolide caused kidney and liver injury, which was associated with systemic inflammatory responses and the activation of hallmarks for PANoptosis in vivo. Collectively, our data reveal that triptolide induces PANoptosis in macrophages in vitro and exhibits nephrotoxicity and hepatotoxicity associated with induction of PANoptosis in vivo, suggesting a new avenue to alleviate triptolide's toxicity by harnessing PANoptosis.


Assuntos
Diterpenos , Fenantrenos , Camundongos , Animais , Apoptose , Macrófagos/metabolismo , Diterpenos/efeitos adversos , Diterpenos/metabolismo , Fenantrenos/toxicidade , Fenantrenos/metabolismo , Compostos de Epóxi/toxicidade , Compostos de Epóxi/metabolismo
18.
J Neuroinflammation ; 20(1): 81, 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36944965

RESUMO

BACKGROUND: Long-term smoking is a risk factor for chronic pain, and chronic nicotine exposure induces pain-like effects in rodents. The anterior cingulate cortex (ACC) has been demonstrated to be associated with pain and substance abuse. This study aims to investigate whether ACC microglia are altered in response to chronic nicotine exposure and their interaction with ACC neurons and subsequent nicotine-induced allodynia in mice. METHODS: We utilized a mouse model that was fed nicotine water for 28 days. Brain slices of the ACC were collected for morphological analysis to evaluate the impacts of chronic nicotine on microglia. In vivo calcium imaging and whole-cell patch clamp were used to record the excitability of ACC glutamatergic neurons. RESULTS: Compared to the vehicle control, the branch endpoints and the length of ACC microglial processes decreased in nicotine-treated mice, coinciding with the hyperactivity of glutamatergic neurons in the ACC. Inhibition of ACC glutamatergic neurons alleviated nicotine-induced allodynia and reduced microglial activation. On the other hand, reactive microglia sustain ACC neuronal excitability in response to chronic nicotine, and pharmacological inhibition of microglia by minocycline or liposome-clodronate reduces nicotine-induced allodynia. The neuron-microglia interaction in chronic nicotine-induced allodynia is mediated by increased expression of neuronal CX3CL1, which activates microglia by acting on CX3CR1 receptors on microglial cells. CONCLUSION: Together, these findings underlie a critical role of ACC microglia in the maintenance of ACC neuronal hyperactivity and resulting nociceptive hypersensitivity in chronic nicotine-treated mice.


Assuntos
Hiperalgesia , Neuralgia , Nicotina , Animais , Camundongos , Giro do Cíngulo/metabolismo , Hiperalgesia/induzido quimicamente , Microglia/metabolismo , Neuralgia/metabolismo , Neurônios/metabolismo , Nicotina/toxicidade
19.
Opt Lett ; 48(8): 2090-2093, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37058649

RESUMO

We demonstrate a stable homodyne phase demodulation method with a double pulse based on an ultra-weak fiber Bragg grating (UWFBG) array. The technique divides one of the probe pulses into three sections and introduces successive 2π/3 phase differences into each section. By using a simple direct detection scheme, it can achieve distributed and quantitative vibration measurement along the UWFBG array. Compared to the traditional homodyne demodulation technique, the proposed technique is more stable and easier to accomplish. Moreover, the reflected light from the UWFBGs can provide a signal that is modulated uniformly by the dynamic strain and multiple results for averaging, resulting in a higher signal-to-noise ratio (SNR). We experimentally demonstrate the technique's effectiveness by monitoring different vibrations. The SNR for measuring a generic 100 Hz, 0.08 rad vibration in a 3 km UWFBG array with a reflectivity of -40 to -45 dB is estimated to be ∼44.92 dB.

20.
Chemistry ; 29(48): e202301121, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37300353

RESUMO

Lithium-sulfur (Li-S) batteries are a promising energy storage technology due to their tempting high theoretical capacity and energy density. Nevertheless, the wastage of active materials that originates from the shuttling effect of polysulfides still hinders advancement of Li-S batteries. The effective design of cathode materials is extremely pivotal to solve this thorny problem. Herein, surface engineering in covalent organic polymers (COPs) has been performed to investigate the influence of pore wall polarity on the performance of COP-based cathodes used for Li-S batteries. With the assistance of experimental investigation and theoretical calculations, performance improvement by increasing pore surface polarity and a synergy effect of the polarized functionalities, along with nano-confinement effect of the COPs, are disclosed, to which the improved performance of Li-S batteries including outstanding Coulombic efficiency (99.0 %) and extremely low capacity decay (0.08 % over 425 cycles at 1.0 C) is attributed. This work not only enlightens the designable synthesis and applications of covalent polymers as polar sulfur hosts with high utilization of active materials, but also provides a feasible guide for the design of effective cathode materials for future advanced Li-S batteries.

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