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1.
J Colloid Interface Sci ; 677(Pt A): 655-664, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39116563

RESUMO

Germanium based nanomaterials are very promising as the anodes for the lithium ion batteries since their large specific capacity, excellent lithium diffusivity and high conductivity. However, their controllable preparation is still very difficult to achieve. Herein, we facilely prepare a unique carbon coating Ge nanospheres with a cubic hollow structure (Ge@C) via a hydrothermal synthesis and subsequent pyrolysis using low-cost GeO2 as precursors. The hollow Ge@C nanostructure not only provides abundant interior space to alleviate the huge volumetric expansion of Ge upon lithiation, but also facilitates the transmission of lithium ions and electrons. Moreover, experiment analyses and density functional theory (DFT) calculations unveil the excellent lithium adsorption ability, high exchange current density, low activation energy for lithium diffusion of the hollow Ge@C electrode, thus exhibiting significant lithium storage advantages with a large charge capacity (1483 mAh/g under 200 mA g-1), distinguished rate ability (710 mAh/g under 8000 mA g-1) as well as long-term cycling stability (1130 mAh/g after 900 cycles under 1000 mA g-1). Therefore, this work offers new paths for controllable synthesis and fabrication of high-performance Ge based lithium storage nanomaterials.

2.
IEEE Trans Cybern ; PP2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39352834

RESUMO

The present study proposes an adaptive fuzzy tracking control strategy for switched nonlinear systems, capable of effectively addressing false data injection (FDI) attacks and input saturation, while achieving flexible prescribed performance control as well as semi-global uniform ultimate boundness for the resultant system. Compared to the previous work, the provided control strategy exhibits two notable strengths: 1) it introduces a novel modified fixed-time pregiven performance function to effectively balance input saturation and output constraint and 2) the detrimental impacts resulting from FDI attacks are successfully mitigated by implementing the fuzzy logic systems approximation technique in the backstepping procedure. A set of switching fuzzy observers are established to estimate the unobservable states while a first-order differential filter is utilized to handle the complexity explosion problem. Finally, the mass-spring-damper system is given to substantiate the developed approach.

3.
Biomed Pharmacother ; 180: 117508, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39362068

RESUMO

Hepatocellular carcinoma (HCC) is a malignant tumor that arises from hepatocytes. Multiple signaling pathways play a regulatory role in the occurrence and development of HCC, with the Wnt signaling pathway being one of the primary regulatory pathways. In normal hepatocytes, the Wnt signaling pathway maintains cell regeneration and organ development. However, when aberrant activated, the Wnt pathway is closely associated with invasion, cancer stem cells(CSCs), drug resistance, and immune evasion in HCC. Among these factors, the development of drug resistance is one of the most important factors affecting the efficacy of HCC treatment. These mechanisms form the basis for tumor cell adaptation and evolution within the body, enabling continuous changes in tumor cells, resistance to drugs and immune system attacks, leading to metastasis and recurrence. In recent years, there have been numerous new discoveries regarding these mechanisms. An increasing number of drugs targeting the Wnt signaling pathway have been developed, with some already entering clinical trials. Therefore, this review encompasses the latest research on the role of the Wnt signaling pathway in the onset and progression of HCC, as well as advancements in its therapeutic strategies.

4.
Int J Biol Macromol ; 281(Pt 1): 136234, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39366602

RESUMO

Cytochrome P450s play a crucial role in the breakdown of external substances and perform important activities in the hormone system of insects. It has been understood that P450s were essential in the metabolism of ecdysteroids. CYP303A1 is a highly conserved CYP in most insects, but its specific physiological functions remain poorly understood in Nilaparvata lugens Stål. In this study, NlCYP303A1 was identified and highly expressed in the pre-molt stages, predominantly in the cuticle-producing tissues. Silencing of NlCYP303A1 caused a lethal phenotype with a molting defect. Moreover, the 20E titers, the expression levels of Halloween genes, and critical genes associated with the 20E signaling pathway in N. lugens nymphs were significantly decreased with the silencing NlCYP303A1. We further performed additional backfilling of 20E to rescue the RNAi effects on NlCYP303A1. The gene expression levels that were previously reduced caused by silencing NlCYP303A1 were significantly elevated. However, the molting defects of nymphs were not effectively improved. The results demonstrated NlCYP303A1 plays a crucial role in the molting and metamorphosis of N. lugens by regulating the 20E signaling pathway and cuticular formation, enhances the understanding of the functional role of CYP 2 clans, and identifies candidate gene for RNAi-based control of N. lugens.

5.
Schizophrenia (Heidelb) ; 10(1): 78, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277614

RESUMO

Cognitive impairment is a core symptom of schizophrenia (SZ), with GABAergic dysfunction in the brain potentially serving as a critical pathological mechanism underlying this condition. Intracortical inhibition (ICI), which includes short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI), can be used to assess the inhibitory function of cortical GABAergic neurons. The aim of this study was to investigate the relationship between ICI and cognitive function, as well as psychopathological symptoms, in SZ patients. We recruited 130 SZ patients and 105 healthy controls (HCs). All subjects underwent paired-pulse transcranial magnetic stimulation (ppTMS) measurements, which included resting motor threshold (RMT), SICI and LICI. The cognitive function of all subjects was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). The psychopathological symptoms of the SZ group were assessed using the Positive and Negative Syndrome Scale (PANSS). We examined group differences in MCCB scores, RMT, SICI, and LICI. Within the SZ group, we assessed the relationship between ICI and cognitive function, as well as psychopathological symptoms. Two-way ANOVA, Mann-Whitney U test, Receiver operating characteristic (ROC) curves, and partial Spearman correlation analysis were performed. The SZ group showed a worse cognitive score in all 6 cognitive dimensions of the MCCB compared to the HC group (all p < 0.05). The SZ group had lower degree of SICI and LICI compared to the HC group (both p < 0.05). ROC curves analysis showed that SICI and LICI all displayed good performance in differentiating SZ patients and HCs (both p < 0.05), and SICI exhibited a better performance, yielding an area under the curve (AUC) of 0.856 (95% CI 0.807-0.904). Furthermore, in the SZ group, SICI demonstrated a significant negative correlation with PANSS positive score, negative score, general psychopathology score, and total score (all pBonferroni < 0.05), and LICI demonstrated a significant negative correlation with PANSS positive score, general psychopathology score and total score (all pBonferroni < 0.05). Additionally, in the SZ group, SICI demonstrated a significant positive correlation with speed of processing score, working memory score, verbal learning score, visual learning score, and reasoning and problem-solving score of the MCCB (all pBonferroni < 0.05), while LICI was only weakly positive correlated with speed of processing score of the MCCB (r = 0.247, p = 0.005, pBonferroni = 0.03). Our results demonstrate that the reduction of ICI could serve as a trait-dependent in-vivo biomarker of GABAergic deficits for SZ and related cognitive impairments.

6.
Genes Dis ; 11(6): 101123, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39281835

RESUMO

FK506-binding protein 9 (FKBP9) is involved in tumor malignancy by resistance to endoplasmic reticulum (ER) stress, and the up-regulation of FKBP9 is associated with patients' poor prognosis. The current knowledge of the molecular mechanisms is still limited. One previous study showed that FKBP9 could confer glioblastoma cell resistance to ER stress through ASK1-p38 signaling. However, the upstream regulatory mechanism of FKBP9 expression is still indistinct. In this study, we identified the FKBP9 binding proteins using co-immunoprecipitation followed by mass spectrometry. Results showed that FKBP9 interacted with the binding immunoglobulin protein (BiP). BiP bound directly to FKBP9 with high affinity. BiP prolonged the half-life of the FKBP9 protein and stabilized the FKBP9 protein. BiP and FKBP9 protein levels were positively correlated in patients with glioma, and patients with high expression of BiP and FKBP9 showed a worse prognosis. Further studies showed that FKBP9 knockout in genetically engineered mice inhibited intracranial glioblastoma formation and prolonged survival by decreasing cellular proliferation and ER stress-induced CHOP-related apoptosis. Moreover, normal cells may depend less on FKBP9, as shown by the absence of apoptosis upon FKBP9 knockdown in a non-transformed human cell line and overall normal development in homozygous knockout mice. These findings suggest an important role of BiP-regulated FKBP9-associated signaling in glioma progression and the BiP-FKBP9 axis may be a potential therapeutic target for glioma.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39287643

RESUMO

Accumulating evidence suggests a role for the tryptophan-kynurenine pathway (TKP) in the psychopathology of major depressive disorder (MDD). Abnormal inflammatory profile and production of TKP neurotoxic metabolites appear more pronounced in MDD with suicidality. Progress in understanding the neurobiology of MDD in adolescents lags significantly behind that in adults due to limited empirical evidence. Aims of this study was to investigate the association between inflammation, TKP, and suicidality in adolescent depression. Seventy-three adolescents with MDD were assessed for serum levels of interleukin (IL)-1ß, IL-6, IL-18, IL-10, tumor necrosis factor-α (TNF-α), tryptophan (TRP), kynurenine (KYN), 3-hydroxykynurenine (3-HK), and kynurenine acid (KA). Correlations between cytokines and TKP measures were examined. Patients were divided into high- (n = 42) and non-high-suicide-risk groups (n = 31), and serum levels of cytokines and TKP metabolites were compared. Significant negative correlations were found between TRP and IL-8 (r = - 0.27, P < 0.05) and IL-10 (r = - 0.23, P < 0.05), while a significant positive correlation was observed between 3-HK and IL-8 (r = 0.39, P < 0.01) in depressed adolescents. The KYN/TPR (index of indoleamine 2,3-dioxygenase, IDO) was positively correlated with IL-1ß (r = 0.34), IL-6 (r = 0.32), IL-10 (r = 0.38) and TNF-α (r = 0.35) levels (P < 0.01); and 3-HK/KYN (index of kynurenine3-monooxidase, KMO) was positively correlated with IL-8 level (r = 0.31, P < 0.01). Depressed adolescents at high suicide risk exhibited significantly higher levels of IL-1ß (Z = 2.726, P < 0.05), IL-10 (Z = 2.444, P < 0.05), and TNF-α (Z = 2.167, P < 0.05) and lower levels of 3-HK (Z = 2.126, P < 0.05) compared to their non-high suicide risk counterparts. Our findings indicated that serum inflammatory cytokines were robustly associated with IDO and KMO activity, along with significantly decreased serum level of TRP, increased level of 3-HK, and higher suicide risk in adolescent depression.

8.
J Integr Neurosci ; 23(9): 169, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39344228

RESUMO

Phagocytosis is the process by which certain cells or organelles internalise foreign substances by engulfing them and then digesting or disposing of them. Microglia are the main resident phagocytic cells in the brain. It is generally believed that microglia/macrophages play a role in guiding the brain's repair and functional recovery processes. However, the resident and invading immune cells of the central nervous system can also exacerbate tissue damage by stimulating inflammation and engulfing viable neurons. The functional consequences of microglial phagocytosis remain largely unexplored. Overall, phagocytosis is considered a beneficial phenomenon in acute brain injury because it eliminates dead cells and induces an anti-inflammatory response. Osteopontin (OPN) is a phosphorylated glycoprotein induced by injury in various tissues, including brain tissue. In acute brain injuries such as hemorrhagic stroke and ischemic stroke, OPN is generally believed to have anti-inflammatory effects. OPN can promote the reconstruction of the blood-brain barrier and up-regulate the scavenger receptor CD36. But in chronic diseases such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), OPN can cause microglia to engulf neurons and worsen disease progression. We explored the role of OPN in promoting microglial phagocytosis in nervous system disorders.


Assuntos
Microglia , Osteopontina , Fagocitose , Osteopontina/metabolismo , Osteopontina/fisiologia , Microglia/metabolismo , Microglia/fisiologia , Fagocitose/fisiologia , Animais , Humanos , Doenças do Sistema Nervoso/metabolismo
9.
J Pain Res ; 17: 2903-2916, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247173

RESUMO

Purpose: Pain management for spinal facet joint (SFJ) and sacroiliac joint (SIJ) pain is challenging, often requiring interventions like radiofrequency ablation (RFA) or corticosteroid injections (CI). This study aims to assess and compare the effectiveness of CI and RFA in treating SFJ and SIJ pain. We combine these treatments due to their shared pathophysiology, similar therapeutic interventions, and the necessity for an integrated approach to spinal pain management. Patients and methods: Literature search from PubMed, Scopus, CENTRAL and Google Scholar for published studies upto 31st December 2023, and reporting data of patients who were treated using CI of RFA for SFJ and SIJ pain. Pooled standardized mean difference (SMD) with a 95% Confidence Interval (CI) was calculated. Results: Our meta-analysis incorporated thirteen studies. Overall, patients, treated with CI had a higher pain intensity score compared to patients treated with RFA (SMD=0.92; 95% CI: 0.19 to 1.65) at 3 months, and at 6 months (SMD=1.53; 95% CI: 0.66 to 2.40) after the treatment. No significant association was reported at 12 months (SMD=1.47; 95% CI: -0.03 to 2.97). Subgroup analysis based on joint types revealed increased pain intensity scores in patients who were treated with CI for SIJ (SMD=1.25; 95% CI: 0.39 to 2.11) and SFJ (SMD=1.33; 95% CI: 0.09 to 2.57) pain. A negative but not significant effect was detected in patients, treated with CI for cervical joint pain (SMD=-0.40; 95% CI: -0.90 to 0.10). Patients treated with CI exhibited higher functional disability score compared to patients treated with RFA at 3 months (SMD=1.28; 95% CI: 0.20 to 2.35) post-treatment. Conclusion: This study suggests that RFA may offer superior pain relief with longer duration compared to steroid injections for spinal facet and sacroiliac joint pain. Decision regarding specific interventions should be individualized and consider patient preferences, clinical context, and potential risks.

10.
Artigo em Inglês | MEDLINE | ID: mdl-39321016

RESUMO

Neural network adaptive iterative learning control (ILC) is developed in this article to treat strict-feedback nonlinear systems with unknown state delays and input saturation. These delays are treated by constructing the Lyapunov-Krasovskii (L-K) functions for each subsystem. A command filter is employed to avoid the derivative explosion caused by continuous differentiation of the virtual controller. Corresponding auxiliary systems are designed and integrated into the backstepping procedure to compensate input saturation and the unimplemented part of the filter. Hyperbolic tangent functions and radial basis function neural networks (RBF NNs) are employed to treat singularity and related unknown terms, respectively. The convergence of the resultant strict-feedback systems is ensured in the framework of composite energy function (CEF). Finally, a simulation example is adopted to substantiate the validity of the proposed algorithm.

11.
Natl Sci Rev ; 11(8): nwae213, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39183748

RESUMO

The prefrontal cortex (PFC) is essential for higher-level cognitive functions. How epigenetic dynamics participates in PFC development and aging is largely unknown. Here, we profiled epigenomic landscapes of rhesus monkey PFCs from prenatal to aging stages. The dynamics of chromatin states, including higher-order chromatin structure, chromatin interaction and histone modifications are coordinated to regulate stage-specific gene transcription, participating in distinct processes of neurodevelopment. Dramatic changes of epigenetic signals occur around the birth stage. Notably, genes involved in neuronal cell differentiation and layer specification are pre-configured by bivalent promoters. We identified a cis-regulatory module and the transcription factors (TFs) associated with basal radial glia development, which was associated with large brain size in primates. These TFs include GLI3, CREB5 and SOX9. Interestingly, the genes associated with the basal radial glia (bRG)-associated cis-element module, such as SRY and SOX9, are enriched in sex differentiation. Schizophrenia-associated single nucleotide polymorphisms are more enriched in super enhancers (SEs) than typical enhancers, suggesting that SEs play an important role in neural network wiring. A cis-regulatory element of DBN1 is identified, which is critical for neuronal cell proliferation and synaptic neuron differentiation. Notably, the loss of distal chromatin interaction and H3K27me3 signal are hallmarks of PFC aging, which are associated with abnormal expression of aging-related genes and transposon activation, respectively. Collectively, our findings shed light on epigenetic mechanisms underlying primate brain development and aging.

12.
Front Immunol ; 15: 1455716, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39185414

RESUMO

Among primary liver cancers, hepatocellular carcinoma is the most common pathological type. Its onset is insidious, and most patients have no obvious discomfort in the early stage, so it is found late, and the opportunity for surgical radical treatment is lost, resulting in a poor prognosis. With the introduction of molecular-targeted drugs represented by sorafenib, patients with middle- and late-stage liver cancer have regained the light of day. However, their therapeutic efficacy is relatively low due to the limited target of drug action, toxic side effects, and other reasons. At this time, the emergence of immunotherapy represented by immune checkpoint inhibitors (ICIs) well breaks this embarrassing situation, which mainly achieves the anti-tumor purpose by improving the tumor immune microenvironment. Currently, ICI monotherapy, as well as combination therapy, has been widely used in the clinic, further prolonging the survival of patients with advanced hepatocellular carcinoma. This article reviews the development of monotherapy and combination therapy for ICIs in advanced hepatocellular carcinoma and the latest research progress.


Assuntos
Carcinoma Hepatocelular , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Animais , Imunoterapia/métodos , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento
13.
Ann Ital Chir ; 95(4): 575-582, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39186330

RESUMO

AIM: Elbow joint release surgery is commonly used to treat elbow joint stiffness. Though it can restore elbow joint mobility, some patients may still experience range of motion (ROM) loss after surgery. Therefore, this study aims to explore the factors influencing ROM loss after elbow joint release surgery in elderly patients with traumatic elbow stiffness. METHODS: This retrospective study included 122 elderly patients with traumatic elbow stiffness who underwent elbow joint release surgery at Hanzhong Central Hospital from January 2023 to April 2024. The patients with range of motion loss were included in the observation group (n = 41), and those without range of motion loss were placed in the control group (n = 81). The general data of the two groups were compared, and Logistic regression analysis was performed to identify factors influencing the loss of ROM after elbow joint release surgery in elderly patients with traumatic elbow stiffness. A risk prediction model was also established based on the identified risk factors. RESULTS: Multivariate Logistic regression analysis unveiled that high-energy injury (odds ratio (OR) = 4.632, 95% confidence interval (CI) = 1.363∼15.737), open injury (OR = 3.967, 95% CI = 1.308∼12.029), passive rehabilitation method (OR = 10.115, 95% CI = 1.113∼91.924), injury-to-release surgery time of ≥6 months (OR = 5.983, 95% CI = 1.677∼21.350), heterotopic ossification traumatic factors (OR = 5.409, 95% CI = 1.316∼22.224), and complex elbow joint damage (OR = 5.658, 95% CI = 1.457∼21.962) were all independent risk factors for ROM loss following elbow joint release surgery in elderly patients with traumatic elbow stiffness (p < 0.05). A risk prediction model was developed based on these factors, indicating a predictive sensitivity of 73.17%, a specificity of 69.14%, and an area under the curve (AUC) of 0.767. CONCLUSIONS: Clinically, the independent risk factors identified in this study should be closely monitored. Furthermore, treatment should be tailored based on the specific conditions of the patient, and high-risk factors should be effectively controlled to reduce the risk of ROM loss after elbow joint release surgery in traumatic elbow joint stiffness elderly patients.


Assuntos
Lesões no Cotovelo , Articulação do Cotovelo , Amplitude de Movimento Articular , Humanos , Estudos Retrospectivos , Articulação do Cotovelo/cirurgia , Articulação do Cotovelo/fisiopatologia , Idoso , Feminino , Masculino , Fatores de Risco , Complicações Pós-Operatórias/etiologia , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade
14.
Int J Surg ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39172720

RESUMO

BACKGROUND: The extensive utilization of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) has achieved significant advancements in the treatment of diverse solid tumors. The present meta-analysis aims to evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) plus PD-1 inhibitor for patients with locally advanced gastric cancer (LAGC). METHODS: An electronic search of PubMed, EmBase, and the Cochrane Library was performed to identify the clinical trials of NCT + PD-1 inhibitor vs. NCT in patients with LAGC. The retrieval period extended from the establishment of the corresponding database until April 2024, and meta-analysis was conducted using Stata (version 15) software. Subsequently, direct comparative analysis was used to compare pooled results of neoadjuvant immunochemotherapy (NICT) with NCT. RESULTS: After screening, 6 phase II/III randomized controlled trials (RCTs) and 9 retrospective studies with 2,953 patients were included. In meta-analysis, NICT group demonstrated a significantly higher rate of pathological complete response (pCR) (P<0.001) and R0 resection (P=0.001), and a lower 2-year recurrence rate (P=0.001) compared to the NCT group. The NICT group, however, exhibited a higher incidence of severe treatment-related adverse events (TRAEs) (P=0.044). Additionally, the NICT and NCT groups exhibited no statistical differences in terms of the number of harvested lymph nodes, the occurrence of total TRAEs and postoperative complications, as well as the duration of postoperative hospitalization. CONCLUSIONS: The combination of PD-1 inhibitor + NCT in LAGC patients enhances the likelihood of achieving radical surgery and improves prognosis, albeit to some extent increasing the risk of severe TRAEs. NICT is anticipated to emerge as the preferred neoadjuvant therapy option for patients diagnosed with LAGC.

15.
Cell Mol Life Sci ; 81(1): 371, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39196413

RESUMO

Current medical therapies for treating acute myeloid leukemia (AML) remain unmet, and AML patients may benefit from targeted immunotherapy approaches that focus on specific tumor antigens. GRP78, which is upregulated in various malignant tumors such as AML, is partially expressed as cell surface GRP78 (csGRP78) on the cell membrane, making it an ideal target for redirecting T cells, including T-cell engagers. However, considering the conventional approach of using two scFv segments to construct a bispecific T-cell engager (BiTE), we have undertaken the development of a novel BiTE that utilizes a cyclic peptide ligand to specifically target csGRP78, which we refer to as GRP78-CD3/BiTE. We studied the effects of GRP78-CD3/BiTE on treatments for AML in vitro and in vivo and assessed the pharmacokinetics of this engager. Our findings demonstrated that GRP78-CD3/BiTE could not only effectively mediate the cytotoxicity of T cells against csGRP78-expressing AML cells but also specifically eliminate primary AML tumor cells in vitro. Furthermore, GRP78-CD3/BiTE exhibited a longer half-life despite having a lower molecular weight than CD19-CD3/BiTE. In a xenograft mouse model of AML, treatment with GRP78-CD3/BiTE prolonged the survival time of the mice. Our findings demonstrate that GRP78-CD3/BiTE is effective and selective for eliminating csGRP78-expressing AML cells and suggest that this approach to targeted immunotherapy could lead to effective new treatments for AML.


Assuntos
Anticorpos Biespecíficos , Chaperona BiP do Retículo Endoplasmático , Leucemia Mieloide Aguda , Linfócitos T , Humanos , Animais , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/tratamento farmacológico , Camundongos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Anticorpos Biespecíficos/imunologia , Anticorpos Biespecíficos/farmacologia , Complexo CD3/imunologia , Proteínas de Choque Térmico/imunologia , Proteínas de Choque Térmico/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Ligantes , Feminino , Camundongos SCID , Imunoterapia/métodos , Camundongos Endogâmicos NOD
16.
Angew Chem Int Ed Engl ; : e202412057, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39132838

RESUMO

Activating anionic redox reaction (ARR) has attracted a great interest in Li/Na-ion batteries owing to the fascinating extra-capacity at high operating voltages. However, ARR has rarely been reported in aqueous zinc-ion batteries (AZIBs) and its possibility in the popular MnO2-based cathodes has not been explored. Herein, the novel manganese deficient MnO2 micro-nano spheres with interlayer "Ca2+-pillars" (CaMnO-140) are prepared via a low-temperature (140 °C) hydrothermal method, where the Mn vacancies can trigger ARR by creating non-bonding O 2p states, the pre-intercalated Ca2+ can reinforce the layered structure and suppress the lattice oxygen release by forming Ca-O configurations. The tailored CaMnO-140 cathode demonstrates an unprecedentedly high rate capability (485.4 mAh g-1 at 0.1 A g-1 with 154.5 mAh g-1 at 10 A g-1) and a marvelous long-term cycling durability (90.6% capacity retention over 5000 cycles) in AZIBs. The reversible oxygen redox chemistry accompanied by CF3SO3- (from the electrolyte) uptake/release, and the manganese redox accompanied by H+/Zn2+ co-insertion/extraction, are elucidated by advanced synchrotron characterizations and theoretical computations. Finally, pouch-type CaMnO-140//Zn batteries manifest bright application prospects with high energy, long life, wide-temperature adaptability, and high operating safety. This study provides new perspectives for developing high-energy cathodes for AZIBs by initiating anionic redox chemistry.

17.
Mol Neurobiol ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164481

RESUMO

Contactin-associated protein1 (Caspr1) plays an important role in the formation and stability of myelinated axons. In Caspr1 mutant mice, autophagy-related structures accumulate in neurons, causing axonal degeneration; however, the mechanism by which Caspr1 regulates autophagy remains unknown. To illustrate the mechanism of Caspr1 in autophagy process, we demonstrated that Caspr1 knockout in primary neurons from mice along with human cell lines, HEK-293 and HeLa, induced autophagy by downregulating the PI3K/AKT/mTOR signaling pathway to promote the conversion of microtubule-associated protein light chain 3 I (LC3-I) to LC3-II. In contrast, Caspr1 overexpression in cells contributed to the upregulation of this signaling pathway. We also demonstrated that Caspr1 knockout led to increased LC3-I protein expression in mice. In addition, Caspr1 could inhibit the expression of autophagy-related 4B cysteine peptidase (ATG4B) protein by directly binding to ATG4B in overexpressed Caspr1 cells. Intriguingly, we found an accumulation of ATG4B in the Golgi apparatuses of cells overexpressing Caspr1; therefore, we speculate that Caspr1 may restrict ATG4 secretion from the Golgi apparatus to the cytoplasm. Collectively, our results indicate that Caspr1 may regulate autophagy by modulating the PI3K/AKT/mTOR signaling pathway and the levels of ATG4 protein, both in vitro and in vivo. Thus, Caspr1 can be a potential therapeutic target in axonal damage and demyelinating diseases.

18.
Sci Rep ; 14(1): 18440, 2024 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-39117844

RESUMO

Camellia oleifera, a significant woody edible oil species, was examined using 48 germplasm resources from high-altitude regions in East Guizhou Province, China, to analyze fruit quality. The analysis aimed to identify high-performance germplasm, providing theoretical and research foundations for selecting and cross-breeding superior C. oleifera varieties in these regions. Fifteen primary traits of mature fruits were measured and analyzed, including four phenotypic traits (single fruit weight, transverse diameter, longitudinal diameter, peel thickness) and eleven quality traits (fresh seed yield rate, dry seed yield rate, dry kernel yield rate, seed kernel oil content, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, α-linolenic acid, cis-11-eicosenoic acid). A comprehensive evaluation employing cluster and principal component analyses (PCA) was conducted. The cluster analysis categorized the germplasms into five groups at a squared Euclidean distance of 14, with the first category comprising 17 germplasms, the second 28, and the third, fourth, and fifth each containing one. PCA reduced the 15 traits to five principal components (PCs), with PC1 having the highest eigenvalue of 3.57 and a contribution rate of 23.8%, mainly representing phenotypic traits. PC2, contributing 20.44%, represented linoleic acid, while PC3, PC4, and PC5, with contribution rates of 12.99%, 9.13%, and 7.45% respectively, predominantly represented seed kernel oil content, fresh seed yield, and palmitoleic acid. Employing a weighted sum method, a comprehensive evaluation function was developed to calculate total scores for each superior individual, forming the basis for rankings and selections. Notable variability was detected in single fruit weight, peel thickness, and fresh and dry seed yields, while oleic acid exhibited the lowest coefficient of variation. Dry seed yield showed a robust positive correlation with seed kernel oil content and the concentrations of palmitic and linoleic acids, whereas seed kernel oil content was inversely correlated with cis-11-eicosenoic acid levels. Five PCs with eigenvalues > 1 were identified, highlighting the top ten superior individuals: QD (Qian Dong: the code of eastern Guizhou Province)-33 > QD-34 > QD-48 > QD-38 > QD-27 > QD-15 > QD-35 > QD-5 > QD-14 > QD-36. Thus, the 48 C. oleifera germplasms from East Guizhou's high-altitude areas demonstrate significant potential for enhancing traits such as single fruit weight, peel thickness, and fresh and dry seed yields. Specifically, QD-33, QD-34, and QD-48 exhibited superior comprehensive performance, designating them as prime candidates for variety selection and breeding.


Assuntos
Altitude , Camellia , Frutas , Camellia/genética , Camellia/crescimento & desenvolvimento , China , Frutas/genética , Frutas/crescimento & desenvolvimento , Sementes , Fenótipo , Análise de Componente Principal , Óleos de Plantas/análise
19.
Adv Mater ; 36(36): e2402971, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39011789

RESUMO

For multicenter-catalyzed reactions, it is important to accurately construct heterogeneous catalysts containing multiple active centers with high activity and low cost, which is more challenging compared to homogeneous catalysts because of the low activity and spatial confinement of active centers in the loaded state. Herein, a convenient protein confinement strategy is reported to locate Pd and Cu single atoms in crowding state on carbon coated alumina for promoting Sonogashira reaction, the most powerful method for constructing the acetylenic moiety in molecules. The single-atomic Pd and Cu centers take advantage in not only the maximized atomic utilization for low cost, but also the much-enhanced performance by facilitating the activation of aryl halides and alkynes. Their locally crowded dispersion brings them closer to each other, which facilitates the transmetallation process of acetylide intermediates between them. Thus, the Sonogashira reaction is drove smoothly by the obtained catalyst with a turnover frequency value of 313 h-1, much more efficiently than that by commercial Pd/C and CuI catalyst, conventional Pd and Cu nanocatalysts, and mixed Pd and Cu single-atom catalyst. The obtained catalyst also exhibits the outstanding durability in the recycling test.

20.
IEEE Trans Cybern ; PP2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012746

RESUMO

This article introduces an adaptive dynamic event-triggered technique for addressing the output tracking control problem of uncertain switched nonlinear systems with prescribed performance. First, a switching dynamic event-triggered mechanism (SDETM) is established to alleviate network burden and conserve computational resources. A notable aspect is the inclusion of asynchronous switching between the switching subsystems and controllers. Second, a state-dependent switching law ensuring a dwell-time constraint is designed, which avoids the frequent switching phenomenon within any finite time interval. Third, an SDETM and an adaptive dynamic event-triggered controller are developed to confine the output tracking error within predefined decaying boundaries, while ensuring that all the signals of the closed-loop switched system remain within bounded regions. Finally, the validity and applicability of the developed control scheme are demonstrated through a one-link manipulator example.

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