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1.
Nature ; 628(8006): 145-153, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38538785

RESUMO

As hippocampal neurons respond to diverse types of information1, a subset assembles into microcircuits representing a memory2. Those neurons typically undergo energy-intensive molecular adaptations, occasionally resulting in transient DNA damage3-5. Here we found discrete clusters of excitatory hippocampal CA1 neurons with persistent double-stranded DNA (dsDNA) breaks, nuclear envelope ruptures and perinuclear release of histone and dsDNA fragments hours after learning. Following these early events, some neurons acquired an inflammatory phenotype involving activation of TLR9 signalling and accumulation of centrosomal DNA damage repair complexes6. Neuron-specific knockdown of Tlr9 impaired memory while blunting contextual fear conditioning-induced changes of gene expression in specific clusters of excitatory CA1 neurons. Notably, TLR9 had an essential role in centrosome function, including DNA damage repair, ciliogenesis and build-up of perineuronal nets. We demonstrate a novel cascade of learning-induced molecular events in discrete neuronal clusters undergoing dsDNA damage and TLR9-mediated repair, resulting in their recruitment to memory circuits. With compromised TLR9 function, this fundamental memory mechanism becomes a gateway to genomic instability and cognitive impairments implicated in accelerated senescence, psychiatric disorders and neurodegenerative disorders. Maintaining the integrity of TLR9 inflammatory signalling thus emerges as a promising preventive strategy for neurocognitive deficits.


Assuntos
Região CA1 Hipocampal , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Inflamação , Memória , Receptor Toll-Like 9 , Animais , Feminino , Masculino , Camundongos , Envelhecimento/genética , Envelhecimento/patologia , Região CA1 Hipocampal/fisiologia , Centrossomo/metabolismo , Disfunção Cognitiva/genética , Condicionamento Clássico , Matriz Extracelular/metabolismo , Medo , Instabilidade Genômica/genética , Histonas/metabolismo , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Memória/fisiologia , Transtornos Mentais/genética , Doenças Neurodegenerativas/genética , Doenças Neuroinflamatórias/genética , Neurônios/metabolismo , Neurônios/patologia , Membrana Nuclear/patologia , Receptor Toll-Like 9/deficiência , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/imunologia , Receptor Toll-Like 9/metabolismo
2.
Sci Adv ; 10(13): eadl4842, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552028

RESUMO

The high-capacity advantage of lithium metal anode was compromised by common use of copper as the collector. Furthermore, lithium pulverization associated with "dead" Li accumulation and electrode cracking deteriorates the long-term cyclability of lithium metal batteries, especially under realistic test conditions. Here, we report an ultralight, integrated anode of polyimide-Ag/Li with dual anti-pulverization functionality. The silver layer was initially chemically bonded to the polyimide surface and then spontaneously diffused in Li solid solution and self-evolved into a fully lithiophilic Li-Ag phase, mitigating dendrites growth or dead Li. Further, the strong van der Waals interaction between the bottommost Li-Ag and polyimide affords electrode structural integrity and electrical continuity, thus circumventing electrode pulverization. Compared to the cutting-edge anode-free cells, the batteries pairing LiNi0.8Mn0.1Co0.1O2 with polyimide-Ag/Li afford a nearly 10% increase in specific energy, with safer characteristics and better cycling stability under realistic conditions of 1× excess Li and high areal-loading cathode (4 milliampere hour per square centimeter).

3.
Front Pharmacol ; 15: 1329307, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318141

RESUMO

With the increasing prevalence of multidrug-resistant Gram-negative bacterial pathogens worldwide, antimicrobial resistance has become a significant public health concern. Ceftazidime-avibactam (CAZ-AVI) exhibited excellent in vitro activity against many carbapenemase-producing pathogens, and was widely used for the treatment of various complicated infections. CAZ-AVI is well tolerated across all dosing regimens, and its associated acute kidney injury (AKI) in phase II/III clinical trials is rare. However, recent real-world studies have demonstrated that CAZ-AVI associated AKI was more frequent in real-world than in phase II and III clinical trials, particularly in patients receiving concomitant nephrotoxic agents, with critically ill patients being at a higher risk. Herein, we reviewed the safety data related to renal impairment of CAZ-AVI, and discussed its pharmacokinetic/pharmacodynamic targets and dosage adjustment in patients with impaired renal function. This review aimed to emphasize the importance for healthcare professionals to be aware of this adverse event of CAZ-AVI and provide practical insights into the dosage optimization in critically ill patients with renal dysfunction.

4.
Angew Chem Int Ed Engl ; 63(13): e202316837, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38315104

RESUMO

The interfacial processes, mainly the lithium (Li) plating/stripping and the evolution of the solid electrolyte interphase (SEI), are directly related to the performance of all-solid-state Li-metal batteries (ASSLBs). However, the complex processes at solid-solid interfaces are embedded under the solid-state electrolyte, making it challenging to analyze the dynamic processes in real time. Here, using in situ electrochemical atomic force microscopy and optical microscopy, we directly visualized the Li plating/stripping/replating behavior, and measured the morphological and mechanical properties of the on-site formed SEI at nanoscale. Li spheres plating/stripping/replating at the argyrodite solid electrolyte (Li6 PS5 Cl)/Li electrode interface is coupled with the formation/wrinkling/inflating of the SEI on its surface. Combined with in situ X-ray photoelectron spectroscopy, details of the stepwise formation and physicochemical properties of SEI on the Li spheres are obtained. It is shown that higher operation rates can decrease the uniformity of the Li+ -conducting networks in the SEI and worsen Li plating/stripping reversibility. By regulating the applied current rates, uniform nucleation and reversible plating/stripping processes can be achieved, leading to the extension of the cycling life. The in situ analysis of the on-site formed SEI at solid-solid interfaces provides the correlation between the interfacial evolution and the electrochemical performance in ASSLBs.

5.
BMC Psychol ; 12(1): 35, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238861

RESUMO

BACKGROUND: One noteworthy concern within the realm of education is the level of engagement demonstrated by students. Among the factor that can have a crucial role in this domain is teacher support, especially emotional support which has an impact on several aspects of learners' education. Furthermore, various studies have investigated the relationship between Emotional Intelligence (EI) and learners' engagement. METHODS: Accordingly, this study investigated the possible role of trait EI and the emotional support of teachers and how these constructs may work to associate learners' engagement. For this objective, a total of 309 Chinese students across different colleges and universities in 5 provinces of Beijing, Shanghai, Jiangsu, Hubei, and Shaanxi were enrolled. They were 126 females and 183 males, with ages ranging from 18 to 30 years old (Mean = 24.6). RESULTS: The results of this research through running Structural Equation Modeling (SEM) demonstrated that teachers' emotional support and trait EI both can associate students' learning engagement. The final measurement model shows that about 73% of changes in learners' engagement can be associated by their trait EI and teachers' emotional support. CONCLUSIONS: This study underscores the importance of emotional support from teachers and the trait of EI in relation to students' engagement in learning. Both factors were shown to play a significant role in associating student engagement. Moreover, this study could potentially have wider impacts on members of academic teams.


Assuntos
Aconselhamento , Pessoal de Educação , Inteligência Emocional , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , China , População do Leste Asiático , Aprendizagem
6.
Lancet Infect Dis ; 24(1): 65-74, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37708908

RESUMO

BACKGROUND: The 2022 global outbreak of mpox (formerly known as monkeypox) spread primarily among gay, bisexual, and other men who have sex with men (GBMSM), with the initial cluster being identified in England in May, 2022. Understanding its epidemiological characteristics and the reasons for its downturn in July, 2022, will help to control future outbreaks. METHODS: We collated data for all diagnosed mpox cases (3621) from England from May 1, 2022, to Nov 16, 2022. Data from 75 individuals with mpox allowed estimation of the incubation period, while data from 121 case-contact pairs were used to estimate the serial interval. Six methods, including a structured dynamic compartmental transmission model, were used to estimate the basic reproduction number (R0). The structured model assumed all male individuals with mpox were GBMSM, who were then stratified into subgroups for those at low risk and high risk for mpox. This best fitting model was used to estimate the reduction in transmissibility, and the effective infectious period (before isolating), that resulted in the outbreak downturn, and the effect of vaccination initiated from June 27, 2022. Bayesian methods were used for parameter estimation and model calibration. FINDINGS: Most cases occurred in men (3544 of 3621, 97·9%). The median incubation period for mpox was 6·90 days (95% credible interval [CrI] 4·08-20·21), and the serial interval was 8·82 days (5·22-25·81). R0 estimates ranged from 1·41 to 2·17. The structured transmission model estimated that 83·8% of infections (95% CrI 83·5-85·3) resulted from sexual partnerships with GBMSM individuals at high risk of mpox. The outbreak downturn probably resulted from a 44·5% reduction in the sexual partner rate among all GBMSM (24·9-55·8) and 20·0% reduction in the effective infectious period (4·1-33·9), preventing 165 896 infections (115 584-217 730). Vaccination marginally increased the number of infections prevented (166 081, 115 745-217 947), but minimised a resurgence in cases from January, 2023, and could have averted four times more infections if initiated earlier. Our findings were sensitive to assumptions regarding the vaccine's effectiveness and the GBMSM subgroup at high risk of mpox. INTERPRETATION: The mpox outbreak in England probably resulted from high sexual partner rates among some GBMSM, with reductions in partner rates reversing the outbreak, and with vaccination minimising future outbreaks. FUNDING: National Institute for Health Research (UK).


Assuntos
Minorias Sexuais e de Gênero , Masculino , Humanos , Teorema de Bayes , Homossexualidade Masculina , Surtos de Doenças/prevenção & controle , Inglaterra/epidemiologia
7.
Discov Oncol ; 14(1): 225, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38063927

RESUMO

OBJECTIVE: To investigate the effect of COVID-19 infection on pancreatic cancer. METHODS: Based on the mRNA-Seq data of COVID-19 patients and pancreatic cancer (PC) patients in the GEO database, we used a support vector machine (SVM), LASSO-Cox regression analysis and random forest tree (RF) to screen the common signature genes of the two diseases and further investigate their effects and functional characteristics on PC, respectively. The above procedures were performed in R software. RESULTS: The proteins COL10A1/FAP/FN1 were found to be common signature genes for COVID-19 and PC, were significantly up-regulated in both diseases and showed good diagnostic efficacy for PC. The risk model based on COL10A1/FAP/FN1 showed good PC risk prediction ability and clinical application potential. Tumor typing based on COL10A1/FAP/FN1 expression levels effectively classified PC into different subtypes and showed significant differences between the two subtypes in terms of survival prognosis, immune levels, immune checkpoint expression levels, mutation status of common tumor mutation sites, and drug sensitivity analysis. While pathway analysis also revealed that FN1 as an extracellular matrix component may be involved in the biological process of PC by regulating the PI3K-AKT signaling axis. CONCLUSION: The upregulated expression of COL10A1/FAP/FN1, the characteristic genes of COVID-19, are potential diagnostic targets for PC, and the upregulated expression of FN1 may promote the progression of PC by activating the PI3K-AKT signaling pathway. The COL10A1/FAP/FN1-based typing provides a new typing approach for PC, and also provides a good reference and idea for the refinement of PC treatment and subsequent clinical research.

8.
BMC Cancer ; 23(1): 1185, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049741

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health concern, necessitating a deeper understanding of its prognosis and underlying mechanisms. This study aimed to investigate the mechanism and prognostic value of CD8+ T Cell exhaustion (CD8+ TEX)-related genes in HCC and construct a survival prognosis prediction model for patients with HCC. METHODS: CD8+ TEX-related genes associated with HCC prognosis were analysed and identified, and a prognostic prediction model was constructed using the 'least absolute shrinkage and selection operator' Cox regression model. Immunohistochemistry was used to verify the expression of the model genes in HCC tissues. A nomogram was constructed based on risk scores and clinical features, and its predictive efficacy was verified. The expression of STAM, ANXA5, and MAD2L2 in HCC cell lines was detected by western blotting; subsequently, these genes were knocked down in HCC cell lines by small interfering RNA, and their effects on the proliferation and migration of HCC cell lines were detected by colony formation assay, cck8, wound healing, and transwell assays. RESULTS: Six genes related to CD8+ TEX were included in the risk-prediction model. The prognosis of patients with HCC in the low-risk group was significantly better than that of those in the high-risk group. Cox regression analysis revealed that the risk score was an independent risk factor for the prognosis of patients with HCC. The differentially expressed genes in patients with high-risk HCC were mainly enriched in the nucleotide-binding oligomerization domain-containing protein-like receptor, hypoxia-inducible factor-1, and tumour programmed cell death protein (PD)-1/PD-L1 immune checkpoint pathways. The CD8+ TEX-related genes STAM, ANXA5, and MAD2L2 were knocked down in HCC cell lines to significantly inhibit cell proliferation and migration. The prediction results of the nomogram based on the risk score showed a good fit and application value. CONCLUSION: The prediction model based on CD8+ TEX-related genes can predict the prognosis of HCC and provide a theoretical basis for the early identification of patients with poor HCC prognosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Exaustão das Células T , Neoplasias Hepáticas/genética , Genes cdc , Anexina A5 , Linfócitos T CD8-Positivos , Prognóstico , Proteínas Mad2
9.
Dev Cell ; 58(23): 2700-2717.e12, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37963469

RESUMO

How dedifferentiated stem-like tumor cells evade immunosurveillance remains poorly understood. We show that the lineage-plasticity regulator SOX9, which is upregulated in dedifferentiated tumor cells, limits the number of infiltrating T lymphocytes in premalignant lesions of mouse basal-like breast cancer. SOX9-mediated immunosuppression is required for the progression of in situ tumors to invasive carcinoma. SOX9 induces the expression of immune checkpoint B7x/B7-H4 through STAT3 activation and direct transcriptional regulation. B7x is upregulated in dedifferentiated tumor cells and protects them from immunosurveillance. B7x also protects mammary gland regeneration in immunocompetent mice. In advanced tumors, B7x targeting inhibits tumor growth and overcomes resistance to anti-PD-L1 immunotherapy. In human breast cancer, SOX9 and B7x expression are correlated and associated with reduced CD8+ T cell infiltration. This study, using mouse models, cell lines, and patient samples, identifies a dedifferentiation-associated immunosuppression mechanism and demonstrates the therapeutic potential of targeting the SOX9-B7x pathway in basal-like breast cancer.


Assuntos
Neoplasias da Mama , Animais , Feminino , Humanos , Camundongos , Linfócitos T CD8-Positivos , Terapia de Imunossupressão , Fatores de Transcrição SOX9 , Inibidor 1 da Ativação de Células T com Domínio V-Set/metabolismo
10.
Nat Commun ; 14(1): 7247, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37945604

RESUMO

Micron-sized Si anode promises a much higher theoretical capacity than the traditional graphite anode and more attractive application prospect compared to its nanoscale counterpart. However, its severe volume expansion during lithiation requires solid electrolyte interphase (SEI) with reinforced mechanical stability. Here, we propose a solvent-induced selective dissolution strategy to in situ regulate the mechanical properties of SEI. By introducing a high-donor-number solvent, gamma-butyrolactone, into conventional electrolytes, low-modulus components of the SEI, such as Li alkyl carbonates, can be selectively dissolved upon cycling, leaving a robust SEI mainly consisting of lithium fluoride and polycarbonates. With this strategy, raw micron-sized Si anode retains 87.5% capacity after 100 cycles at 0.5 C (1500 mA g-1, 25°C), which can be improved to >300 cycles with carbon-coated micron-sized Si anode. Furthermore, the Si||LiNi0.8Co0.1Mn0.1O2 battery using the raw micron-sized Si anode with the selectively dissolved SEI retains 83.7% capacity after 150 cycles at 0.5 C (90 mA g-1). The selective dissolution effect for tailoring the SEI, as well as the corresponding cycling life of the Si anodes, is positively related to the donor number of the solvents, which highlights designing high-donor-number electrolytes as a guideline to tailor the SEI for stabilizing volume-changing alloying-type anodes in high-energy rechargeable batteries.

11.
Zhongguo Zhong Yao Za Zhi ; 48(15): 4237-4242, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37802792

RESUMO

This study aims to evaluate the effectiveness and economic efficiency of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of chronic rhinosinusitis(CRS). The randomized controlled trial(RCT) of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of CRS was searched against EMbase, PubMed, Cochrane Library, CNKI, VIP, SinoMed, and Wanfang. The efficacy, nasal mucociliary transport time, and safety of the therapy above in the treatment of CRS were analyzed with single-group rate and Meta-analysis, and the economy and sensitivity were evaluated from the perspective of payer. A total of 9 RCTs were included, including 1 145 patients. Meta-analysis showed that compared with Triamcinolone Acetonide Nasal Spray alone, Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of CRS patients increased the effective rate(RR=1.17, 95%CI[1.11, 1.24], P<0.000 01) and shortened the nasal mucociliary transport time(MD=-3.32, 95%CI[-5.86,-0.78], P=0.01), there was no significant difference in the incidence of adverse reactions between the two groups. The incremental cost-effectiveness analysis showed that the treatment costs of the control group and the observation group were 44.15 yuan and 1 044.96 yuan, respectively. In the Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray treatment group, 75.48 yuan was spent to improve the effective rate of CRS by 1%. The one-way sensitivity analysis indicated the days of treatment, the RR of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray, the price of unit preparation of Biyuan Tongqiao Granules, and the effective rate of Triamcinolone Acetonide Nasal Spray alone had great influence on the incremental cost-effectiveness ratio. In conclusion, Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray improves the therapeutic effect on CRS. The probabilistic sensitivity analysis showed that when the willingness to pay was greater than 7 920 yuan(less than 0.1 of GDP per capita 8 098 yuan), the combined therapy was economically superior to the control. Due to the limited number of articles published, it is necessary to carry out a real-world clinical trial of Biyuan Tongqiao Gra-nules and Triamcinolone Acetonide Nasal Spray in the treatment of CRS, so as to compare the cost-effectiveness of Biyuan Tongqiao Granules and Triamcinolone Acetonide Nasal Spray.


Assuntos
Sinusite , Triancinolona Acetonida , Humanos , Triancinolona Acetonida/uso terapêutico , Triancinolona Acetonida/efeitos adversos , Sprays Nasais , Análise de Custo-Efetividade , Sinusite/tratamento farmacológico , Doença Crônica
12.
Artigo em Inglês | MEDLINE | ID: mdl-37874752

RESUMO

Ionogels are increasingly used in flexible strain sensors, but it is still challenging to incorporate multifunctional properties such as flexibility, self-healing, adhesion, temperature resistance, and electrical conductivity. Herein, a facile and rapid one-step photoinitiated polymerization strategy is employed to prepare multifunctional ionogels by filling a hydrophobic and conductive ionic liquid into a flexible, hydrophobic fluoropolymer matrix. Thanks to the presence of abundant noncovalent interactions (hydrogen-bonding and ion-dipole interactions), the ionogels exhibit high transparency, excellent mechanical properties, self-healing ability, and adhesion. Moreover, rich C-F bonds in the fluoropolymer matrix can eliminate the interference of water molecules, resulting in excellent environmental tolerance such as high and low temperature resistance, waterproofness, and anticorrosion. Furthermore, the ionogel-based wearable strain sensor can sensitively detect and differentiate human movements and subtle muscle movements and serve as a Morse code signal transmitter for information transmission. The presented work provides an effective method to develop versatile flexible conductive ionogels for wearable devices and ionotronics.

13.
Front Oncol ; 13: 1206043, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37664040

RESUMO

Cancer secondary to dermatomyositis (DM) is defined as paraneoplastic dermatomyositis, which is one of the major subtypes of DM. However, cases of DM with intrahepatic cholangiocarcinoma (ICC) are rarely reported. In the course of our clinical work, we encountered a case of a middle-aged female patient who was diagnosed with DM for 7 years and then diagnosed with ICC, and we would like to share this case. In addition, in order to further investigate the deeper mechanism of ICC associated with DM, we also analyzed the dataset related to DM and ICC in the Gene Expression Omnibus (GEO) database based on the machine learning methods and found that poly(ADP-ribose) polymerase family member 12 (PARP12) and metallothionein 1M (MT1M) were closely associated with ICC secondary to DM. They are potentially important biomarkers for predicting the occurrence of ICC in patients with DM.

14.
Elife ; 122023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37665325

RESUMO

The telencephalon and eye in mammals are originated from adjacent fields at the anterior neural plate. Morphogenesis of these fields generates telencephalon, optic-stalk, optic-disc, and neuroretina along a spatial axis. How these telencephalic and ocular tissues are specified coordinately to ensure directional retinal ganglion cell (RGC) axon growth is unclear. Here, we report self-formation of human telencephalon-eye organoids comprising concentric zones of telencephalic, optic-stalk, optic-disc, and neuroretinal tissues along the center-periphery axis. Initially-differentiated RGCs grew axons towards and then along a path defined by adjacent PAX2+ VSX2+ optic-disc cells. Single-cell RNA sequencing of these organoids not only confirmed telencephalic and ocular identities but also identified expression signatures of early optic-disc, optic-stalk, and RGCs. These signatures were similar to those in human fetal retinas. Optic-disc cells in these organoids differentially expressed FGF8 and FGF9; FGFR inhibitions drastically decreased early RGC differentiation and directional axon growth. Through the RGC-specific cell-surface marker CNTN2 identified here, electrophysiologically excitable RGCs were isolated under a native condition. Our findings provide insight into the coordinated specification of early telencephalic and ocular tissues in humans and establish resources for studying RGC-related diseases such as glaucoma.


Assuntos
Glaucoma , Células Ganglionares da Retina , Animais , Humanos , Retina , Axônios , Telencéfalo , Mamíferos
15.
Funct Integr Genomics ; 23(4): 312, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37775648

RESUMO

Recent advances in immunotherapeutic approaches have the potential to bring new hope to the treatment of pancreatic cancer. The tumor microenvironment contributes significantly to tumor development and progression. In this study, miR-429 overexpression was found to inhibit proliferation, invasion, and clonogenicity while promoting apoptosis in HepG2 cells. Furthermore, co-culture of miR-429-overpressing or silenced HepG2 cells with PBMCs showed that miR-429 induced CD4+ and CD8+ T cell infiltration, decreased the numbers of Tregs, inhibited CD8+ T cell apoptosis and exhaustion, and enhanced CD8+ T cell functions in PBMCs. miR-429 was found to prevent an immunosuppressive HCC microenvironment by targeting and suppressing PD-L1. In a C57BL/6 mouse subcutaneous xenograft tumor model, overexpression of miR-429 reduced tumorigenesis and both tumor volumes and weights were decreased relative to controls. In addition, CD4+ and CD8+ T cells were increased, Tregs were reduced, and CD8+ T cell apoptosis and depletion were reduced in the tumor tissues induced by miR-429-overexpressing HepG2 cells.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Animais , Humanos , Camundongos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamento farmacológico , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Microambiente Tumoral
16.
J Cell Mol Med ; 27(17): 2467-2481, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37594177

RESUMO

Prematurely-born infants cared for in the neonatal units suffer from memory and learning deficits. Prematurity diminishes neurogenesis and synaptogenesis in the hippocampal dentate gyrus (DG). This dysmaturation of neurons is attributed to elevated PSD95, NMDR2A, and IGF1 levels. Since oestrogen treatment plays key roles in the development and plasticity of DG, we hypothesized that 17ß-estradiol (E2) treatment would ameliorate neurogenesis and synaptogenesis in the DG, reversing cognitive deficits in premature newborns. Additionally, E2-induced recovery would be mediated by IGF1 signalling. These hypotheses were tested in a rabbit model of prematurity and nonmaternal care, in which premature kits were gavage-fed and reared by laboratory personnel. We compared E2- and vehicle-treated preterm kits for morphological, molecular, and behavioural parameters. We also treated kits with oestrogen degrader, RAD1901, and assessed IGF1 signalling. We found that E2 treatment increased the number of Tbr2+ and DCX+ neuronal progenitors and increased the density of glutamatergic synapses in the DG. E2 treatment restored PSD95 and NMDAR2A levels and cognitive function in preterm kits. Transcriptomic analyses showed that E2 treatment contributed to recovery by influencing interactions between IGF1R and neurodegenerative, as well as glutamatergic genes. ERα expression was reduced on completion of E2 treatment at D7, followed by D30 elevation. E2-induced fluctuation in ERα levels was associated with a reciprocal elevation in IGF1/2 expression at D7 and reduction at D30. ERα degradation by RAD1901 treatment enhanced IGF1 levels, suggesting ERα inhibits IGF1 expression. E2 treatment alleviates the prematurity-induced maldevelopment of DG and cognitive dysfunctions by regulating ERα and IGF1 levels.


Assuntos
Receptor alfa de Estrogênio , Estrogênios , Animais , Coelhos , Tetra-Hidronaftalenos , Receptores de Estrogênio , Proteína 4 Homóloga a Disks-Large/genética , Giro Denteado
17.
J Exp Med ; 220(10)2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37549024

RESUMO

The neuro-immune regulation is associated with homeostasis of the intestine. Intestinal group 3 innate lymphoid cells (ILC3s) are tissue-resident lymphocytes whose functions are affected by the intestine niche. However, how a gut neuronal signal coordinates the immune response of ILC3s is largely unknown. Here, we found that cyclic adenosine monophosphate (cAMP) signaling exacerbated the inflammatory response and attenuated the expression level of the transcription factor forkhead box O1 (FOXO1) in ILC3s. Deficiency of FOXO1 drove the hyperactivation of ILC3s and resulted in gut inflammation independently of T cells. Mechanistically, FOXO1 promoted the transcription of neuropeptide receptor VIPR2 and inhibited the transcription of adrenoceptor ADRA2A in ILC3s. FOXO1-related regulation of VIPR2 and ADRA2A signaling balanced the activation of ILC3s under steady condition or during colitis. Moreover, chronic stress elevated cAMP level and downregulated FOXO1 level, exacerbating intestinal inflammation. Our findings reveal that FOXO1 balances the activation of ILC3s via VIP and adrenergic signaling and regulates intestinal homeostasis.


Assuntos
Imunidade Inata , Linfócitos , Humanos , Transdução de Sinais , Inflamação/metabolismo , Homeostase , Proteína Forkhead Box O1/metabolismo
18.
Angew Chem Int Ed Engl ; 62(33): e202305988, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37339945

RESUMO

Ether solvents with superior reductive stability promise excellent interphasial stability with high-capacity anodes while the limited oxidative resistance hinders their high-voltage operation. Extending the intrinsic electrochemical stability of ether-based electrolytes to construct stable-cycling high-energy-density lithium-ion batteries is challenging but rewarding. Herein, the anion-solvent interactions were concerned as the key point to optimize the anodic stability of the ether-based electrolytes and an optimized interphase was realized on both pure-SiOx anodes and LiNi0.8 Mn0.1 Co0.1 O2 cathodes. Specifically, the small-anion-size LiNO3 and tetrahydrofuran with high dipole moment to dielectric constant ratio realized strengthened anion-solvent interactions, which enhance the oxidative stability of the electrolyte. The designed ether-based electrolyte enabled a stable cycling performance over 500 cycles in pure-SiOx ||LiNi0.8 Mn0.1 Co0.1 O2 full cell, demonstrating its superior practical prospects. This work provides new insight into the design of new electrolytes for emerging high-energy density lithium-ion batteries through the regulation of interactions between species in electrolytes.

20.
BMC Neurol ; 23(1): 219, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291501

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of computed tomography (CT)-guided microwave ablation combined with vertebral augmentation under real-time temperature monitoring in the treatment of painful osteogenic spinal metastases. METHODS: This retrospective study included 38 patients with 63 osteogenic metastatic spinal lesions treated using CT-guided microwave ablation and vertebral augmentation under real-time temperature monitoring. Visual analog scale scores, daily morphine consumption, and Oswestry Disability Index scores were used to evaluate efficacy of the treatment. RESULTS: Microwave ablation combined with vertebral augmentation reduced the mean visual analog scale scores from 6.40 ± 1.90 preoperatively to 3.32 ± 0.96 at 24 h, 2.24 ± 0.91 at 1 week, 1.92 ± 1.32 at 4 weeks, 1.79 ± 1.45 at 12 weeks, and 1.39 ± 1.12 at 24 weeks postoperatively (all p < 0.001). The mean preoperative daily morphine consumption was 108.95 ± 56.41 mg, which decreased to 50.13 ± 25.46 mg at 24 h, 31.18 ± 18.58 mg at 1 week, 22.50 ± 16.63 mg at 4 weeks, 21.71 ± 17.68 mg at 12 weeks, and 17.27 ± 16.82 mg at 24 weeks postoperatively (all p < 0.001). During the follow-up period, the Oswestry Disability Index scores significantly reduced (p < 0.001). Bone cement leakage occurred in 25 vertebral bodies, with an incidence of 39.7% (25/63). CONCLUSIONS: The results indicate that microwave ablation combined with vertebral augmentation under real-time temperature monitoring is a feasible, effective, and safe treatment for painful osteoblast spinal metastases.


Assuntos
Fraturas da Coluna Vertebral , Neoplasias da Coluna Vertebral , Humanos , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/secundário , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Temperatura , Resultado do Tratamento , Medição da Dor , Dor , Morfina/uso terapêutico
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