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1.
ACS Nano ; 2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39418110

RESUMEN

Activating the STING pathway in the cytosol of tumor-infiltrating antigen-presenting cells (APCs) represents a promising strategy to elicit potent antitumor immune responses for cancer therapy. However, STING agonists are mostly small hydrophilic molecules that suffer from rapid clearance and poor cytosolic delivery following systemic administration. While various nanoparticles have been developed to promote cytosolic delivery, they often exhibit premature drug release during circulation. Alternatively, stable nanoparticles with sustained release during circulation have poor cytosolic delivery. In this study, we have developed physically cross-linked hyaluronic acid (HA) and lipid hybrid nanoparticles containing cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), denoted as HLHC, to address these challenges. The HLH delivery system has sustained drug release due to multiple lipid layers physically cross-linked by HA. HLHC efficiently delivers cGAMP to the cytosol of APCs, inducing more IFNß than cGAMP and liposomal cGAMP. HLH also improves the drug circulation time and biodistribution to the tumor compared with the liposomal formulation and free drug. Strikingly, a single dose of HLHC, but not liposomal cGAMP or free cGAMP, elicits potent antitumor immunity and regresses established MC38 tumors. A single dose of HLHC even regresses established B16F10 tumors upon combination with αPD-L1. Moreover, cured animals were protected from rechallenge with the same tumor cells. HLHC represents an efficient strategy to address delivery challenges associated with STING agonists and may have broad applications for the delivery of drugs acting in the cytosol.

2.
J Agric Food Chem ; 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39415482

RESUMEN

Plant growth-promoting rhizobacteria (PGPR) can promote lateral root formation, while the underlying mechanisms are not fully understood. Here, we found that Pseudomonas chlororaphis subsp. aurantiaca inoculation enhanced auxin accumulation in lateral root primordia (LRP). Upon reaching LRPs, auxin activated the AUXIN RESPONSE FACTOR 7 and 19 (ARF7/19) and promoted lateral root formation in Arabidopsis. Moreover, we found that reactive oxygen species (ROS) is required for auxin-dependent lateral root emergence, and P. chlororaphis upregulated the expression of RESPIRATORY BURST OXIDASE D and F (RBOHD/F), leading to the accumulation of ROS in LRP. Although scavenging ROS or rbohd/f mutants exhibited decreased lateral roots after P. chlororaphis inoculation, the bacteria-triggered auxin signals were not altered. Conversely, the application of auxin or mutants defective in auxin signaling disturbed P. chlororaphis-derived ROS accumulation in lateral roots. Collectively, these results suggest that ARF7/19-dependent auxin signaling activates RBOHD/F to produce ROS, coordinately facilitating lateral root development after P. chlororaphis treatment.

3.
Eur J Clin Nutr ; 2024 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-39433856

RESUMEN

In recent years, the prevalence of metabolic diseases has increased significantly, posing a serious threat to global health. Chronic low-grade inflammation is implicated in the development of most metabolic diseases, such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia, and cardiovascular disease, serving as a link between diet and these conditions. Increasing attention has been directly toward dietary inflammatory patterns that may prevent or ameliorate metabolic diseases. The Dietary Inflammatory Index (DII) was developed to assess the inflammatory potential of dietary intake. Consequently, a growing body of research has examined the associations between the DII and the risk of several metabolic diseases. In this review, we explore the current scientific literature on the relationships between the DII, T2DM, obesity, and dyslipidemia. It summarizes recent findings and explore potential underlying mechanisms from two aspects: the interaction between diet and inflammation, and the link between inflammation and metabolic diseases. Furthermore, this review discusses the therapeutic strategies, including dietary modifications, prebiotics, and probiotics, and discusses the application of the DII in metabolic diseases, as well as future research directions.

4.
ACS Sens ; 9(10): 5578-5586, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39415079

RESUMEN

Herein, a label-free single-molecule electrical sensor was first proposed for the ultrasensitive and selective detection of iodide ions in human urine. Single-molecule conductance measurements in different halogen ion solutions via scanning tunneling microscopy break junction (STM-BJ) clearly revealed that I- ions strongly affect the stability and displacement distance (Δz) distribution of molecular junctions. Theoretical calculations prove that the specific adsorption of I- ions modifies the surface properties and weakens the molecular adsorption. Furthermore, the average conductance peak area versus the logarithm of the I- ion concentration has a very good linear relationship in the range of 5 × 10-6 to 5 × 10-10 M, with a correlation coefficient of 0.99. This quantitative analysis remains valid in the presence of interfering ions of SO42-, ClO4-, Br-, and Cl- as well as interfering molecules of ascorbic acid, uric acid, dopamine, and cysteine. A cross-comparison of the human urine detection results of this single-molecule electrical sensor with those of the clinical method of As3+-Ce4+ catalytic spectrophotometry revealed an average difference of 0.9%, which decreased the detection time of 2 h with the traditional method to approximately 15 min. This work proves the promising practical potential of the single-molecule electrical technique for relevant clinical analysis.


Asunto(s)
Yoduros , Humanos , Yoduros/orina , Yoduros/química , Límite de Detección , Técnicas Electroquímicas/métodos
5.
Environ Res ; 263(Pt 3): 120166, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39419259

RESUMEN

Nitrate pollution in groundwater is a global environmental issue that poses significant threats to human health and ecological security. This study focuses on elucidating the mechanisms of heterotrophic-autotrophic cooperative denitrification (HAD) by employing wheat straw and elemental sulfur as electron donors in varying proportions. The research initially underscores that heterotrophic denitrification (HD) accelerates the denitrification process due to its high-energy metabolism. However, as readily degradable organic matter diminished, reliance on more complex substrates such as lignocellulose posed a challenge to HD. This marks a pivotal transition towards autotrophic denitrification (AD), which, despite a slower initial rate, exhibits a more sustained denitrification performance. A low proportion of heterotrophic denitrification layer (e.g., 3:1) at the bottom facilitating efficient and sustainable denitrification. HD is capable of simultaneous removal of nitrates and nitrites, whereas AD demonstrates a higher affinity for nitrates, with nitrite accumulation reaching 100% at high influent nitrate concentrations (100 mg/L). HD not only provides the necessary alkaline environment for AD but also reduces sulfate production, whereas AD utilizes the residual organic carbon and ammonia produced by HD. The heterotrophic layer is characterized by a diverse community, whereas the autotrophic layer is predominantly composed of Thiobacillus. By delineating the interactive mechanisms and characteristics of HAD, this study highlights the importance of balancing heterotrophic and autotrophic activities for the effective remediation of groundwater nitrates.

6.
Int J Biol Macromol ; 280(Pt 2): 135792, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39304052

RESUMEN

Recently, the important role of fatty acid (FA) metabolism in cancers has been highlighted. Sirtuin 3 (SIRT3) is determined as an important regulator in the FA metabolism of cancer cells. We are going to verify whether and how lncRNA transmembrane phosphatase with tensin homology pseudogene 1 (TPTEP1) and SIRT3 may exert certain impact on the FA metabolism in triple-negative breast cancer (TNBC). Firstly, TPTEP1 was verified to be with low expression in TNBC cells. Moreover, down-regulation of TPTEP1 was caused by YY1 transcription factor. Functional assays determined the effects of TPTEP1 on the process of TNBC. The results disclosed that TPTEP1 up-regulation significantly repressed cell proliferation, migration, invasion, EMT and the reprogramming of FA metabolism in TNBC. Mechanism experiments detected the regulatory mechanism between TPTEP1 and SIRT3, which turned out that TPTEP1 positively regulated SIRT3 to affect FOXO3a and inhibit the Wnt/ß-catenin pathway via sponging miR-1343-3p. All in all, TPTEP1 functioned as a tumor suppressor to regulate TNBC progression via the miR-1343-3p/SIRT3/FOXO3a/Wnt/ß-catenin signaling.

7.
Cancer Lett ; 605: 217278, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39332588

RESUMEN

As one of the important members of the family of chemokines and their receptors, the CXCL13/CXCR5 axis is involved in follicle formation in normal lymphoid tissues and the establishment of somatic cavity immunity under physiological conditions, as well as being associated with a wide range of infectious, autoimmune, and tumoral diseases. Here in this review, we focus on its role in tumors. Traditional studies have found the axis to be both pro- and anti-tumorigenic, involving a variety of immune cells, including the tumor cells themselves and those in the tumor microenvironment (TME), and the prognostic significance of this axis is clinical context-dependent. With the development of techniques at the single-cell level, we were able to explain in detail the status of the CXCL13/CXCR5 axis in the TME based on real clinical samples and found that it involves a range of crucial intrinsic anti-tumor immune processes in the TME and is therefore important in tumor immunotherapy. We summarize the cellular subsets, physiological functions, and prognostic significance associated with this axis in the most promising immune checkpoint inhibitor (ICI) therapies of the day and summarize possible therapeutic ideas based on this axis. As with any TME study, the most important takeaway is that the complexity of the CXCL13/CXCR5 axis in TME suggests the importance of personalized therapy in tumor therapy.

8.
Inflammation ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39088122

RESUMEN

The cGAS-STING-mediated antiviral response plays an important role in the defense against DNA virus infection. Tripartite motif protein 35 (TRIM35), an E3 ubiquitin ligase, was identified as a positive regulator of RLR-mediated antiviral signaling in our previous study, but the effect of TRIM35 on the cGAS-STING signaling pathway has not been elucidated. Herein, we showed that TRIM35 negatively regulates the cGAS-STING signaling pathway by directly targeting STING. TRIM35 overexpression significantly inhibited the cGAMP-triggered phosphorylation of TBK1 and IRF3, attenuating IFN-ß expression and the downstream antiviral response. Mechanistically, TRIM35 colocalized and directly interacted with STING in the cytoplasm. TRM35 removed K63-linked ubiquitin from STING through the C36 and C44 sites in the RING domain, which impaired the interaction of STING with TBK1 or IKKε. In addition, we demonstrated that the RING domain is a key region for the antiviral effects of TIRM35. These results collectively indicate that TRIM35 negatively regulates type I interferon (IFN-I) production by targeting and deubiquitinating STING. TRIM35 may be a potential therapeutic target for controlling viral infection.

9.
Nat Nanotechnol ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39209994

RESUMEN

In patients with glioblastoma (GBM), upregulated midkine (MDK) limits the survival benefits conferred by temozolomide (TMZ). RNA interference (RNAi) and CRISPR-Cas9 gene editing technology are attractive approaches for regulating MDK expression. However, delivering these biologics to GBM tissue is challenging. Here we demonstrate a polymer-locking fusogenic liposome (Plofsome) that can be transported across the blood-brain barrier (BBB) and deliver short interfering RNA or CRISPR-Cas9 ribonucleoprotein complexes into the cytoplasm of GBM cells. Plofsome is designed by integrating a 'lock' into the fusogenic liposome using a traceless reactive oxygen species (ROS)-cleavable linker so that fusion occurs only after crossing the BBB and entering the GBM tissue with high ROS levels. Our results showed that MDK suppression by Plofsomes significantly reduced TMZ resistance and inhibited GBM growth in orthotopic brain tumour models. Importantly, Plofsomes are effective only at tumour sites and not in normal tissues, which improves the safety of combined RNAi and CRISPR-Cas9 therapeutics.

10.
Pharmacol Res ; 208: 107357, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39159732

RESUMEN

Aberrant energy metabolism in the brain is a common pathological feature in the preclinical Alzheimer's Disease (AD). Recent studies have reported the early elevations of glycolysis-involved enzymes in AD brain and cerebrospinal fluid according to a large-scale proteomic analysis. It's well-known that astrocytes exhibit strong glycolytic metabolic ability and play a key role in the regulation of brain homeostasis. However, its relationship with glycolytic changes and cognitive deficits in early AD patients is unclear. Here, we investigated the mechanisms by which astrocyte glycolysis is involved in early AD and its potential as a therapeutic target. Our results suggest that Aß-activated microglia can induce glycolytic-enhanced astrocytes in vitro, and that these processes are dependent on the activation of the AKT-mTOR-HIF-1α pathway. In early AD models, the increase in L-lactate produced by enhanced glycolysis of astrocytes leads to spatial cognitive impairment by disrupting synaptic plasticity and accelerating Aß aggregation. Furthermore, we find rapamycin, the mTOR inhibitor, can rescue the impaired spatial memory and Aß burden by inhibiting the glycolysis-derived L-lactate in the early AD models. In conclusion, we highlight that astrocytic glycolysis plays a critical role in the early onset of AD and that the modulation of glycolysis-derived L-lactate by rapamycin provides a new strategy for the treatment of AD.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Astrocitos , Glucólisis , Ácido Láctico , Animales , Femenino , Masculino , Ratones , Ratas , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Glucólisis/efectos de los fármacos , Ácido Láctico/metabolismo , Trastornos de la Memoria/metabolismo , Ratones Endogámicos C57BL , Microglía/metabolismo , Microglía/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo
11.
Int J Biol Macromol ; 278(Pt 2): 134770, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39151862

RESUMEN

Lightweight, flexible, efficient and easy-to-manufacture electromagnetic interference (EMI) shielding materials are in urgent demand in the communications industry, artificial intelligence and wearable electronics. Based on the large size difference between one-dimensional carboxymethyl cellulose nanofibers (CMC) and large-diameter silver nanowires (AgNWs), layered AgNWs/CMC nanocomposite films with large effective thickness, and high conductivity were first prepared by a simple one-step vacuum filtration self-assembly technique. The unique layered structure of the AgNWs/CMC nanocomposite film significantly enhances the conductive pathways within the film, endowing it excellent EMI shielding performance. The results show that the conductivity of the ultra-thin film with a thickness of 20 µm is 3.72 × 106 S/m, and the EMI SE in the X-band is 87.7 dB, which can effectively shield electromagnetic signals in mobile communications. Furthermore, the AgNWs/CMCs nanocomposite films exhibit excellent thermal management performance, which can be heated to 100-180 °C within 10 s at a low voltage of 1.5 V. In particular, this nanocomposite film with a new layered structure provides a noval preparation idea for future EMI shielding materials and wearable heating devices.


Asunto(s)
Carboximetilcelulosa de Sodio , Nanocompuestos , Nanofibras , Nanocables , Plata , Plata/química , Nanocompuestos/química , Nanocables/química , Nanofibras/química , Carboximetilcelulosa de Sodio/química , Conductividad Eléctrica , Fenómenos Electromagnéticos
12.
Phys Chem Chem Phys ; 26(34): 22491-22497, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39145725

RESUMEN

Enhanced dielectric constant and high breakdown strength offers immense promise for excellent energy storage performance, which is of critical significance in modern electronics and power systems. However, polymer nanocomposites with traditional routes have to balance between dielectric constant and breakdown strength, hence hindering substantive increases in energy density. Herein, a sandwiched polymer nanocomposite film has been constructed to take full advantage of the individual component layers. BaTiO3 nanoparticles are coated with a fluoropolymer to form core-shell structures and then introduced into a polymer as the top and the bottom layers of a sandwich film for enhancing polarization. Moreover, boron nitride nanosheets (BNNSs) in the middle layer of the sandwich film exert positive effects on the inhibition of current leakage for high breakdown resistance. The breakdown strength increases from 480 MV m-1 of the neat polymer to 580 MV m-1 of the sandwiched film. Additionally, the film exhibits a higher dielectric constant in comparison with the neat polymer. The sandwiched film displays a superior energy density (15.75 J cm-3), which is about 1.9 times that of the neat polymer. This work proposes a feasible route to achieve excellent energy storage of polymer dielectrics by synergistically introducing insulating fillers and additional dipoles in a sandwiched polymer nanocomposite film.

13.
Eur J Radiol ; 179: 111664, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39121745

RESUMEN

OBJECTIVES: To investigate whether high concentration iodinated contrast media (CM), compared with low concentration CM, could reduce pain and discomfort levels in patients who had level II and III venous conditions. METHODS: This prospective, single-center study enrolled patients who had level II and III venous conditions and underwent abdominal contrast-enhanced CT scan between July 2021 and February 2022. The venous condition to establish peripheral venous access for CM injection was graded using the Intravenous Access Scoring system, of which level II and III indicated poor venous condition and difficult venous access. Patients received iomeprol 400 in high concentration group and ioversol 320 in low group at an identical iodine delivery rate of 1.12 gI/s. The primary outcomes were pain and comfort levels. The secondary outcomes included adverse events and image quality. Patients rated pain intensity via Numerical Rating Scale and comfort level via Visual Analogue Scale with higher scores indicating higher levels of pain and discomfort. Quantitative and qualitative image assessment were compared between two groups. Continuous variables were compared using Student's t test or Mann-Whitney U test. Categorical variables were compared using χ2 test, χ2 test for trend or Fisher's exact test. RESULTS: A total of 206 patients (mean age, 60.13 ± 12.14 years; 81 males) were included with 99 in the high concentration group and 107 in the low concentration group. The high group had significantly lower pain scores (median 1 [IQR: 0-2] vs 2 (IQR 2-4), p < 0.001) and comfort scores (1 [IQR: 0-3] vs 3 [IQR: 2-5], p < 0.001) than the low group. Incidence of CM extravasation did not significantly differ (1.0 % vs 4.5 %, p = 0.214). No hypersensitivity reaction was observed. Qualitative assessment showed higher clarity scores of intrahepatic hepatic artery and portal vein in the high group. Quantitative assessment results were comparable between two groups. CONCLUSION: High concentration iodinated CM could lower pain intensity and improve comfort levels without comprising image quality of CT scan. High concentration CM is a preferable choice in patients with poor venous conditions during contrast-enhanced CT scan.


Asunto(s)
Medios de Contraste , Yopamidol , Dimensión del Dolor , Tomografía Computarizada por Rayos X , Humanos , Medios de Contraste/efectos adversos , Medios de Contraste/administración & dosificación , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía Computarizada por Rayos X/métodos , Yopamidol/análogos & derivados , Yopamidol/administración & dosificación , Yopamidol/efectos adversos , Ácidos Triyodobenzoicos/efectos adversos , Ácidos Triyodobenzoicos/administración & dosificación , Anciano , Radiografía Abdominal/métodos , Dolor Abdominal/diagnóstico por imagen , Dolor Abdominal/prevención & control , Dolor Abdominal/inducido químicamente
14.
Int J Biol Macromol ; 279(Pt 2): 135193, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39216584

RESUMEN

The Myeloblastosis (MYB) transcription factor (TF) family is one of the largest transcription factor families in plants and plays an important role in various physiological processes. At present, there are few reports on birch (Betula platyphylla Suk.) of R2R3-MYB-TFs, and most BpMYBs still need to be characterized. In this study, 111 R2R3-MYB-TFs with conserved R2 and R3 MYB domains were identified. Phylogenetic tree analysis showed that the MYB family members of Arabidopsis thaliana and birch were divided into 23 and 21 subgroups, respectively. The latter exhibited an uneven distribution across 14 chromosomes. There were five tandem duplication events and 17 segmental duplication events between BpMYBs, and repeat events play an important role in the expansion of the family. In addition, the promoter region of MYBs was rich in various cis-acting elements, and MYB-TFs were involved in plant growth and development, light responses, biotic stress, and abiotic stress. RNA-sequencing (RNA-seq) and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results revealed that most R2R3-MYB-TFs in birch responded to salt stress. In particular, the expression of BpMYBs in the S20 subfamily was significantly induced by salt, drought, abscisic acid, and methyl jasmonate stresses. Based on the weighted co-expression network analysis of physiological and RNA-seq data of birch under salt stress, a key MYB-TF BpMYB95 (BPChr12G24087), was identified in response to salt stress, and its expression level was induced by salt stress. BpMYB95 is a nuclear localization protein with transcriptional activation activity in yeast and overexpression of this gene significantly enhanced salt tolerance in Saccharomyces cerevisiae. The qRT-PCR and histochemical staining results showed that BpMYB95 exhibited the highest expression in the roots, young leaves, and petioles of birch plants. Overexpression of BpMYB95 significantly improved salt-induced browning and wilting symptoms in birch leaves and alleviated the degree of PSII photoinhibition caused by salt stress in birch seedlings. In conclusion, most R2R3-MYB-TFs found in birch were involved in the salt stress response mechanisms. Among these, BpMYB95 was a key regulatory factor that significantly enhanced salt tolerance in birch. The findings of this study provide valuable genetic resources for the development of salt-tolerant birch varieties.


Asunto(s)
Betula , Regulación de la Expresión Génica de las Plantas , Filogenia , Proteínas de Plantas , Tolerancia a la Sal , Factores de Transcripción , Betula/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Tolerancia a la Sal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genoma de Planta , Estrés Fisiológico/genética , Estrés Salino/genética , Plantas Modificadas Genéticamente/genética
15.
Nanomaterials (Basel) ; 14(13)2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38998761

RESUMEN

Sulfurized polyacrylonitrile (SPAN) is a promising cathode material for lithium-sulfur batteries owing to its reversible solid-solid conversion for high-energy-density batteries. However, the sluggish reaction kinetics of SPAN cathodes significantly limit their output capacity, especially at high cycling rates. Herein, a CNT-interpenetrating hierarchically porous SPAN electrode is developed by a simple phase-separation method. Flexible self-supporting SPAN cathodes with fast electron/ion pathways are synthesized without additional binders, and exceptional high-rate cycling performances are obtained even with substantial sulfur loading. For batteries assembled with this special cathode, an impressive initial discharge capacity of 1090 mAh g-1 and a retained capacity of 800 mAh g-1 are obtained after 1000 cycles at 1 C with a sulfur loading of 1.5 mg cm-2. Furthermore, by incorporating V2O5 anchored carbon fiber as an interlayer with adsorption and catalysis function, a high initial capacity of 614.8 mAh g-1 and a notable sustained capacity of 500 mAh g-1 after 500 cycles at 5 C are achieved, with an ultralow decay rate of 0.037% per cycle with a sulfur loading of 1.5 mg cm-2. The feasible construction of flexible SPAN electrodes with enhanced cycling performance enlists the current processing as a promising strategy for novel high-rate lithium-sulfur batteries and other emerging battery electrodes.

16.
BMC Cancer ; 24(1): 850, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39020297

RESUMEN

BACKGROUND: This study was designed to evaluate the effect of progesterone receptor (PR) status on the prognosis of advanced estrogen receptor (ER)-high human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients receiving CDK4/6 inhibitor combined with endocrine as first-line therapy. METHODS: Advanced ER-high HER2-negative breast cancer patients who were admitted to Harbin Medical University Cancer Hospital and received cyclin-dependent kinase (CDK)4/6 inhibitor combined with endocrine as first-line therapy were included for analysis. Patients were divided into PR-high group (11-100%), PR-low group (1-10%), and PR-negative group (< 1%) according to the expression of PR. Chi-square test was used to analyze the correlation of variables between groups. COX regression analysis were used to analyze the risk factors of survival. Kaplan-Meier survival curve was used to analyze the differences of progression-free survival (PFS) and overall survival (OS) between groups. RESULTS: Among the 152 patients, 72 were PR-high, 32 were PR-low, and 48 were PR-negative. Compared with PR-negative group, the proportions of disease-free survival (DFS) ≥ 5 years and Ki-67 index ≤ 30% in PR-low group and PR-high group were significant higher. PR-negative patients were more likely to occur first-line progression of disease within 24 months (POD24) than PR-high(P = 0.026). Univariate and multivariate analysis showed that PR-negative and first-line POD24 occurrence were risk factors for survival. Survival curve analysis showed that compared with PR-high group, the PFS and OS were significantly lower in PR-negative group (P = 0.001, P = 0.036, respectively). Patients with first-line POD24 had shorter OS in the overall population as well as in subgroups stratified by PR status. CONCLUSIONS: PR-negative and first-line POD24 occurrence were risk factors of advanced ER-high HER2-negative breast cancer patients receiving CDK4/6 inhibitor combined with endocrine as first-line therapy. PR-negative patients had shortest PFS and OS. Regardless of PR status, first-line POD24 occurrence predicted shorter OS.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Receptor ErbB-2 , Receptores de Estrógenos , Receptores de Progesterona , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Persona de Mediana Edad , Receptores de Estrógenos/metabolismo , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Pronóstico , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Inhibidores de Proteínas Quinasas/uso terapéutico , Estimación de Kaplan-Meier , Estudios Retrospectivos , Antineoplásicos Hormonales/uso terapéutico
17.
Adv Mater ; 36(36): e2407751, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39011791

RESUMEN

In the pursuit of artificial neural systems, the integration of multimodal plasticity, memory retention, and perceptual functions stands as a paramount objective in achieving neuromorphic perceptual components inspired by the human brain, to emulating the neurological excitability tuning observed in human visual and respiratory collaborations. Here, an artificial visual-respiratory synapse is presented with monolayer oxidized MXene (VRSOM) exhibiting synergistic light and atmospheric plasticity. The VRSOM enables to realize facile modulation of synaptic behaviors, encompassing postsynaptic current, sustained photoconductivity, stable facilitation/depression properties, and "learning-experience" behavior. These performances rely on the privileged photocarrier trapping characteristics and the hydroxyl-preferential selectivity inherent of oxidized vacancies. Moreover, environment recognitions and multimodal neural network image identifications are achieved through multisensory integration, underscoring the potential of the VRSOM in reproducing human-like perceptual attributes. The VRSOM platform holds significant promise for hardware output of human-like mixed-modal interactions and paves the way for perceiving multisensory neural behaviors in artificial interactive devices.


Asunto(s)
Sinapsis , Sinapsis/fisiología , Humanos , Oxidación-Reducción , Materiales Biomiméticos/química , Redes Neurales de la Computación , Respiración
18.
Plant Signal Behav ; 19(1): 2371694, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38916149

RESUMEN

MYB transcription factor is one of the largest families in plants. There are more and more studies on plants responding to abiotic stress through MYB transcription factors, but the mechanism of some family members responding to salt stress is unclear. In this study, physiological and transcriptome techniques were used to analyze the effects of the R2R3-MYB transcription factor AtMYB72 on the growth and development, physiological function, and key gene response of Arabidopsis thaliana. Phenotypic observation showed that the damage of overexpression strain was more serious than that of Col-0 after salt treatment, while the mutant strain showed less salt injury symptoms. Under salt stress, the decrease of chlorophyll content, the degree of photoinhibition of photosystem II (PSII) and photosystem I (PSI) and the degree of oxidative damage of overexpressed lines were significantly higher than those of Col-0. Transcriptome data showed that the number of differentially expressed genes (DEGs) induced by salt stress in overexpressed lines was significantly higher than that in Col-0. GO enrichment analysis showed that the response of AtMYB72 to salt stress was mainly by affecting gene expression in cell wall ectoplast, photosystem I and photosystem II, and other biological processes related to photosynthesis. Compared with Col-0, the overexpression of AtMYB72 under salt stress further inhibited the synthesis of chlorophyll a (Chla) and down-regulated most of the genes related to photosynthesis, which made the photosynthetic system more sensitive to salt stress. AtMYB72 also caused the outbreak of reactive oxygen species and the accumulation of malondialdehyde under salt stress, which decreased the activity and gene expression of key enzymes in SOD, POD, and AsA-GSH cycle, thus destroying the ability of antioxidant system to maintain redox balance. AtMYB72 negatively regulates the accumulation of osmotic regulatory substances such as soluble sugar (SS) and soluble protein (SP) in A. thaliana leaves under salt stress, which enhances the sensitivity of Arabidopsis leaves to salt. To sum up, MYB72 negatively regulates the salt tolerance of A. thaliana by destroying the light energy capture, electron transport, and antioxidant capacity of Arabidopsis.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Estrés Oxidativo , Fotosíntesis , Hojas de la Planta , Estrés Salino , Arabidopsis/genética , Arabidopsis/efectos de los fármacos , Arabidopsis/fisiología , Arabidopsis/metabolismo , Fotosíntesis/efectos de los fármacos , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Estrés Salino/genética , Estrés Oxidativo/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Complejo de Proteína del Fotosistema II/metabolismo , Complejo de Proteína del Fotosistema I/metabolismo , Clorofila/metabolismo
19.
Neuropharmacology ; 257: 110034, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38878858

RESUMEN

Clinical surgery can lead to severe neuroinflammation and cognitive dysfunctions. It has been reported that astrocytes mediate memory formation and postoperative cognitive dysfunction (POCD), however, the thalamic mechanism of astrocytes in mediating POCD remains unknown. Here, we report that reactive astrocytes in zona incerta (ZI) mediate surgery-induced recognition memory impairment in male mice. Immunostaining results showed that astrocytes are activated with GABA transporter-3 (GAT-3) being down-expressed, and neurons were suppressed in the ZI. Besides, our work revealed that reactive astrocytes caused increased tonic current in ZI neurons. Up-regulating the expression of GAT-3 in astrocytes ameliorates surgery-induced recognition memory impairment. Together, our work demonstrates that the reactive astrocytes in the ZI play a crucial role in surgery-induced memory impairment, which provides a new target for the treatment of surgery-induced neural dysfunctions.


Asunto(s)
Astrocitos , Proteínas Transportadoras de GABA en la Membrana Plasmática , Trastornos de la Memoria , Regulación hacia Arriba , Zona Incerta , Animales , Masculino , Proteínas Transportadoras de GABA en la Membrana Plasmática/metabolismo , Trastornos de la Memoria/metabolismo , Ratones , Regulación hacia Arriba/efectos de los fármacos , Astrocitos/metabolismo , Zona Incerta/metabolismo , Ratones Endogámicos C57BL , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/prevención & control , Reconocimiento en Psicología/efectos de los fármacos , Reconocimiento en Psicología/fisiología
20.
Fundam Res ; 4(1): 131-139, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38933849

RESUMEN

Solar-driven CO2-to-fuel conversion assisted by another major greenhouse gas CH4 is promising to concurrently tackle energy shortage and global warming problems. However, current techniques still suffer from drawbacks of low efficiency, poor stability, and low selectivity. Here, a novel nanocomposite composed of interconnected Ni/MgAlO x nanoflakes grown on SiO2 particles with excellent spatial confinement of active sites is proposed for direct solar-driven CO2-to-fuel conversion. An ultrahigh light-to-fuel efficiency up to 35.7%, high production rates of H2 (136.6 mmol min-1g- 1) and CO (148.2 mmol min-1g-1), excellent selectivity (H2/CO ratio of 0.92), and good stability are reported simultaneously. These outstanding performances are attributed to strong metal-support interactions, improved CO2 absorption and activation, and decreased apparent activation energy under direct light illumination. MgAlO x @SiO2 support helps to lower the activation energy of CH* oxidation to CHO* and improve the dissociation of CH4 to CH3* as confirmed by DFT calculations. Moreover, the lattice oxygen of MgAlO x participates in the reaction and contributes to the removal of carbon deposition. This work provides promising routes for the conversion of greenhouse gasses into industrially valuable syngas with high efficiency, high selectivity, and benign sustainability.

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