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1.
World J Gastrointest Surg ; 16(7): 2167-2174, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39087123

RESUMO

BACKGROUND: In recent years, pure laparoscopic radical surgery for Bismuth-Corlette type III and IV hilar cholangiocarcinoma (HCCA) has been preliminarily explored and applied, but the surgical strategy and safety are still worthy of further improvement and attention. AIM: To summarize and share the application experience of the emerging strategy of "hepatic hilum area dissection priority, liver posterior separation first" in pure laparoscopic radical resection for patients with HCCA of Bismuth-Corlette types III and IV. METHODS: The clinical data and surgical videos of 6 patients with HCCA of Bismuth-Corlette types III and IV who underwent pure laparoscopic radical resection in our department from December 2021 to December 2023 were retrospectively analyzed. RESULTS: Among the 6 patients, 4 were males and 2 were females. The average age was 62.2 ± 11.0 years, and the median body mass index was 20.7 (19.2-24.1) kg/m2. The preoperative median total bilirubin was 57.7 (16.0-155.7) µmol/L. One patient had Bismuth-Corlette type IIIa, 4 patients had Bismuth-Corlette type IIIb, and 1 patient had Bismuth-Corlette type IV. All patients successfully underwent pure laparoscopic radical resection following the strategy of "hepatic hilum area dissection priority, liver posterior separation first". The operation time was 358.3 ± 85.0 minutes, and the intraoperative blood loss volume was 195.0 ± 108.4 mL. None of the patients received blood transfusions during the perioperative period. The median length of stay was 8.3 (7.0-10.0) days. Mild bile leakage occurred in 2 patients, and all patients were discharged without serious surgery-related complications. CONCLUSION: The emerging strategy of "hepatic hilum area dissection priority, liver posterior separation first" is safe and feasible in pure laparoscopic radical surgery for patients with HCCA of Bismuth-Corlette types III and IV. This strategy is helpful for promoting the modularization and process of pure laparoscopic radical surgery for complicated HCCA, shortens the learning curve, and is worthy of further clinical application.

2.
Anal Chem ; 96(29): 11881-11889, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38976239

RESUMO

Both solitary and tandem applications of residual chemical shift anisotropy (RCSA) and residual dipolar coupling (RDC) show great potential for the structural and configurational determination of organic molecules. A critical component of both RDC and RCSA methodologies is the alignment medium, whose availability is limited, especially for RCSA measurement. Moreover, reported RDC and RCSA acquisitions mainly rely on two experiments conducted under two different conditions, which are relatively time-consuming and easily cause experimental errors. Herein, a biphasic supramolecular lyotropic liquid crystalline (LLC) system was developed through the self-assembly of C21H43-CONH-V4K3-CONH2, which could act as an alignment medium for not only RDC but also RCSA extraction in DMSO-d6. Notably, the RCSA extraction was easily achieved via one-shot measurement from a single one-dimensional 13C NMR experiment, with no need for special instruments, devices, and correction. Relying on the biphasic LLC medium, meanwhile, RDC data were simply extracted from a single F1-coupled HSQC experiment, different from the standard protocol that requires two spectral acquisitions corresponding to the isotropic and anisotropic conditions. Collectively, the biphasic LLC medium is applicable for tandem RCSA and RDC measurements in one single sample, advancing the stereochemical elucidation of molecules of interest.

3.
Anal Chim Acta ; 1317: 342916, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39030013

RESUMO

BACKGROUND: Protein misfolding and aggregation can lead to various diseases. Recent studies have shed light on the aggregated protein in breast cancer pathology, which suggests that it is crucial to design chemical sensors that visualize protein aggregates in breast cancer, especially in clinical patient-derived samples. However, most reported sensors are constrained in cultured cell lines. RESULTS: In this work, we present the development of two isophorone-based crystallization-induced-emission fluorophores for detecting proteome aggregation in breast cancer cell line and tissues biopsied from diseased patients, designated as A1 and A2. These probes exhibited viscosity sensitivity and recovered their fluorescence strongly at crystalline state. Moreover, A1 and A2 exhibit selective binding capacity and strong fluorescence for various aggregated proteins. Utilizing these probes, we detect protein aggregation in stressed breast cancer cells, xenograft mouse model of human breast cancer and clinical patient-derived samples. Notably, the fluorescence intensity of both probes light up in tumor tissues. SIGNIFICANCE: The synthesized isophorone-based crystallization-induced-emission fluorophores, A1 and A2, enable sensitive detection of protein aggregation in breast cancer cells and tissues. In the future, aggregated proteins are expected to become indicators for early diagnosis and clinical disease monitoring of breast cancer.


Assuntos
Neoplasias da Mama , Cristalização , Corantes Fluorescentes , Proteoma , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Animais , Feminino , Corantes Fluorescentes/química , Proteoma/análise , Proteoma/química , Camundongos , Agregados Proteicos , Linhagem Celular Tumoral , Camundongos Nus
4.
J Phys Chem A ; 128(30): 6167-6182, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39038260

RESUMO

The 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) flame retardants (DOPO-FRs) have attracted more and more attention in the flame-retardant industry due to their high efficiency, environmental protection, and good molecular design. During the flame-retardant process, the breakage of P-C bonds is very important to the flame-retardant effect. Through the comparison of different density functional theories (DFTs) on P-C BDEs, it was found that MN12-L has the highest calculation accuracy, and the root-mean-square error is the smallest with 1.85 kcal/mol. Therefore, MN12-L was selected to investigate P-C BDEs of different DOPO-FRs including thiophen-amine, benzo[d]thiazol-amine, triazol-amine, and aniline DOPO-FRs. By comparing the theoretical calculation of BDE with the experimental parameters of high limiting oxygen index (LOI) and vertical combustion test (UL-94 test), it was found that the P-C BDEs have a certain correlation with the flame-retardant effect. Finally, based on P-C BDEs, substituent effects, and effective flame-retardant fragments, a series of new DOPO-FRs were designed. The results showed that when only one DOPO fragment was contained, the effective fragments of flame retardants were ranked as furan > thiophene > triazole > imidazole. When bis-DOPO fragment was contained, the flame-retardant effect of diamino-triazole fragments was better than that of benzyldimethylamine fragments. In addition, when the substituents on the effective fragment have two EDGs, the flame-retardant effect is superimposed, which makes the flame-retardant performance more excellent.

5.
J Sep Sci ; 47(12): e2400247, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39031562

RESUMO

Glutathione (GSH) is an important antioxidant that is generated and degraded via the GSH cycle. Quantification of the main components in the GSH cycle is necessary to evaluate the process of GSH. In this study, a robust ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of 10 components (GSH; γ-glutamylcysteine; cysteinyl-glycine; n-acetylcysteine; homocysteine; cysteine; cystine; methionine; glutamate; pyroglutamic acid) in GSH cycle was developed. The approach was optimized in terms of derivative, chromatographic, and spectrometric conditions as well as sample preparation. The unstable thiol groups of GSH, γ-glutamylcysteine, cysteinyl-glycine, n-acetylcysteine, cysteine, and homocysteine were derivatized by n-ethylmaleimide. The derivatized and underivatized analytes were separated on an amino column with gradient elution. The method was further validated in terms of selectivity (no interference), linearity (R2 > 0.99), precision (% relative standard deviation [RSD%] range from 0.57 to 10.33), accuracy (% relative error [RE%] range from -3.42 to 10.92), stability (RSD% < 5.68, RE% range from -2.54 to 4.40), recovery (RSD% range from 1.87 to 7.87) and matrix effect (RSD% < 5.42). The validated method was applied to compare the components in the GSH cycle between normal and oxidative stress cells, which would be helpful in clarifying the effect of oxidative stress on the GSH cycle.


Assuntos
Glutationa , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Glutationa/análise , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Homocisteína/análise , Cisteína/análise , Ácido Pirrolidonocarboxílico/análise , Ácido Pirrolidonocarboxílico/química , Ácido Pirrolidonocarboxílico/metabolismo , Dipeptídeos/análise , Acetilcisteína/análise , Acetilcisteína/química , Cistina/análise
6.
World J Gastrointest Oncol ; 16(7): 2867-2876, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39072175

RESUMO

Hepatocellular carcinoma (HCC) is a systemic disease with augmented malignant degree, high mortality and poor prognosis. Since the establishment of the immune mechanism of tumor therapy, people have realized that immunotherapy is an effective means for improvement of HCC patient prognosis. Oncolytic virus is a novel immunotherapy drug, which kills tumor cells and exempts normal cells by directly lysing tumor and inducing anti-tumor immune response, and it has been extensively examined as an HCC therapy. This editorial discusses oncolytic viruses for the treatment of HCC, emphasizing viral immunotherapy strategies and clinical applications related to HCC.

7.
J Clin Neurosci ; 126: 319-327, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39018828

RESUMO

BACKGROUND: Artificial lumbar disc replacement is an effective method for the treatment of lumbosacral degenerative diseases. An appropriate artificial intervertebral disc device is of great significance for the maintenance of spinal stability and activity. METHODS: Two finite element models of ProDisc-L prosthesis replacement and improved prosthesis replacement were constructed by using the finite element model of complete lumbar L1-L5 segment established by CT image data. The mechanical properties of the surgical models before and after improvement were analyzed and evaluated. RESULTS: The ProDisc-L group and the improved group showed similar lumbar's ROM and maintained a similar ROM with the normal lumbar spine. There was no significant change in the intervertebral disc's pressure between the adjacent segments of the two prosthesis groups compared with the normal group, but the stress value of the improved prosthesis group was slightly lower than that of the ProDisc-L group. In addition, the improved prosthesis replacement has more reasonable stress distribution. CONCLUSIONS: Compared with the ProDisc-L prosthesis, the improved prosthesis can reduce the pressure in the intervertebral disc of the adjacent segment, the contact stress of the facet joint and the artificial prosthesis, which provides reference for the subsequent design of the prosthesis structure.


Assuntos
Análise de Elementos Finitos , Vértebras Lombares , Substituição Total de Disco , Humanos , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Substituição Total de Disco/métodos , Substituição Total de Disco/instrumentação , Disco Intervertebral/cirurgia , Disco Intervertebral/diagnóstico por imagem , Fenômenos Biomecânicos/fisiologia , Amplitude de Movimento Articular/fisiologia , Desenho de Prótese , Próteses e Implantes , Masculino , Degeneração do Disco Intervertebral/cirurgia , Degeneração do Disco Intervertebral/diagnóstico por imagem
8.
Sci Rep ; 14(1): 16629, 2024 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025912

RESUMO

This study explores migrasomes' role in neuroblastoma, a common malignant tumor in children, and their potential impact on tumor formation. We analyzed neuroblastoma RNA-seq datasets from public databases, including GSE62564, GSE181559, target, and fwr144. Through data normalization and unsupervised classification using migrasome-specific molecular markers, Differentially Expressed Genes were identified, followed by functional enrichment analysis. Our novel migrasome-associated machine learning model, MigScore, was developed using ten algorithms and 101 combinations, validated on two single-cell datasets. This enabled immune infiltration assessment and drug compatibility prediction, highlighting the utility of MS275, a histone deacetylase inhibitor. Results showed a significant inverse relationship between MigScore and favorable clinical outcomes, elucidating the link between migrasome pathways and tumor immunogenicity. These findings suggest that migrasomes are crucial in neuroblastoma prognosis, leading to the possibility of personalized treatment strategies and improved outcomes.


Assuntos
Aprendizado de Máquina , Neuroblastoma , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Neuroblastoma/mortalidade , Humanos , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Perfilação da Expressão Gênica , Algoritmos , Multiômica
9.
Free Radic Biol Med ; 223: 96-108, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39067624

RESUMO

The biological role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Apex1) in modulating systemic inflammation remains unclear. This study aimed to assess the impact of Apex1 deficiency on systemic inflammation triggered by lipopolysaccharide (LPS) in a murine model. The methods involved transcriptomic analysis and assessments of inflammatory responses in age-matched 8-week-old Apex1+/- and wild-type Apex1+/+ mice, generated using the CRISPR/Cas9 system. Apex1+/- mice displayed no overt changes in body weight, however, Apex1 protein expressions in tissues were significantly reduced compared to wild-type mice. Furthermore, in Apex1+/- mice transcriptomic analysis showed that genes associated with antioxidant pathways were downregulated, and levels of superoxide production, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malondialdehyde (MDA) were increased. Moreover, hematological analysis showed increased neutrophil levels and a twofold increase in the count of splenic lymphocyte antigen 6 family member G+ (Ly6G+) neutrophils in the Apex1+/- mice compared to those in Apex1+/+ mice. Furthermore, following LPS treatment, the levels of cytokines and chemokines, including interleukin-1ß, interleukin-10, tumor necrosis factor-α, and monocyte chemoattractant protein 1, increased in the Apex1+/- mice. The Kaplan-Meier curve showed a significant reduction in the survival rates of Apex1+/- mice treated with LPS compared to those of Apex1+/+ mice. The hepatic and lung injury scores and Ly6G+ neutrophil infiltration levels also increased in Apex1+/- mice after LPS treatment. These results showed that Apex1 deficiency exacerbated the LPS-induced tissue damage in the lung and liver. These findings illustrate that in vivo Apex1 deficiency exacerbates LPS-induced systemic inflammation, tissue damage, and mortality in a murine model, highlighting the crucial role of Apex1 in mitigating inflammatory responses and maintaining a holistic physiological equilibrium.

10.
J Dairy Sci ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38825103

RESUMO

Traditional fermented milks are produced through an inoculation process that involves the deliberate introduction of microorganisms that have been adapted and perpetuated across successive generations. However, the changes in the microbiota of traditional fermented milk during long-term inoculation fermentation in a laboratory environment remain unclear. In this study, we collected 5 samples of traditional fermented milk samples from 5 different counties in Tibet (3 kurut products) and Xinjiang (2 tarag products) of China, which served as starter cultures for a 9-mo continuous inoculation fermentation experiment. We analyzed the inter- and intra-population variations in the microbial communities of the collected samples, representing their macrodiversity and microdiversity, using shotgun metagenomic sequencing. Across all samples, we obtained a total of 186 high-quality metagenomic-assembled genomes, including 7 genera and 13 species with a relative abundance of more than 1%. The majority of these genomes were annotated as Lactobacillus helveticus (60.46%), Enterococcus durans (9.52%), and Limosilactobacillus fermentum (6.23%). We observed significant differences in species composition and abundance among the 5 initial inoculants. During the long-term inoculation fermentation, we found an overall increasing trend in species diversity, composition, and abundances of carbohydrate metabolism module-encoding genes in the fermented milk bacterial metagenome, while the fermented milk virome exhibited a relatively narrow range of variation. Lactobacillus helveticus, a dominant species in traditional fermented milk, displayed high stability during the long-term inoculation fermentation. Our study provides valuable insights for the industrial production of traditional fermented milk.

11.
Biology (Basel) ; 13(6)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38927318

RESUMO

Tea saponins have high surface-active and biological activities and are widely used in chemicals, food, pharmaceuticals, and pesticides. Tea saponins are usually extracted using ethanol or water, but both methods have their disadvantages, including a negative impact on the environment, high energy consumption, and low purity. In this study, we explored an effective process for extracting tea saponins from tea meal using deep eutectic solvents combined with ultrasonic extraction and enzymatic techniques. The experimental results showed that a high extraction efficiency of 20.93 ± 0.48% could be achieved in 20 min using an ultrasonic power of 40% and a binary DES consisting of betaine and ethylene glycol (with a molar ratio of 1:3) at a material-liquid ratio of 1:35 and that the purity of the tea saponins after purification by a large-pore adsorption resin reached 95.94%, which was higher than that of commercially available standard tea saponin samples. In addition, the extracted tea saponins were evaluated for their antioxidant and bacteriostatic activities using chemical and biological methods; the results showed that the tea saponins extracted using these methods possessed antioxidant properties and displayed significant antibacterial activity. Therefore, the present study developed a method for using deep eutectic solvents as an environmentally friendly technological solution for obtaining high-purity tea saponins from tea meal oil. This is expected to replace the current organic solvent and water extraction process and has great potential for industrial development and a number of possible applications.

12.
Pol Arch Intern Med ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934851

RESUMO

INTRODUCTION: The role of iron homeostasis has become increasingly recognized as a key factor in determining the prognosis of patients with heart failure (HF). Disruptions in iron balance, encompassing deficiency and overload, can affect patient prognosis, therefore, these indicators are considered of significant implications for treatment and management strategies. OBJECTIVES: The current study intends to delve into the association between iron homeostasis-related indicators and long-term mortality as well as first-admission mortality in individuals with HF. PATIENTS AND METHODS: Data on 3483 HF patients from the MIMIC IV database were retrospectively analyzed. The relationship between iron homeostasis-related indicators (ferritin, serum iron, transferrin, and total iron binding capacity [TIBC]) and the prognosis of HF patients was discerned utilizing the Cox proportional hazards model and Kaplan-Meier survival analysis. Additionally, the predictive capability of these indicators for patient prognosis was assessed using receiver operating characteristic curve (ROC). RESULTS: Fourth quartile levels of ferritin and serum iron were obviously associated with poor long-term outcomes in HF patients. Conversely, fourth quartile levels of transferrin and TIBC served as protective factors and were associated with a better prognosis. Additionally, iron homeostasis indicators exhibited a certain predictive value for both long-term mortality and first-admission mortality in HF patients. CONCLUSIONS: This study underscores the significant association between iron homeostasis indicators and the prognosis of HF patients, providing valuable insights for risk stratification and clinical decision-making for this population. Future studies should focus on the dynamic fluctuations in patients' iron homeostasis and explore intervention measures to improve the prognosis of HF patients.

13.
Sci Rep ; 14(1): 13108, 2024 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849383

RESUMO

LHPP has been shown to be a new tumor suppressor, and has a tendency to be under-expressed in a variety of cancers. Oncolytic virotheray is a promising therapeutics for lung cancer in recent decade years. Here we successfully constructed a new recombinant oncolytic adenovirus GD55-LHPP and investigated the effect of GD55-LHPP on the growth of lung cancer cells in vitro and in vivo. The results showed that LHPP had lower expression in either lung cancer cells or clinical lung cancer tissues compared with normal cells or tissues, and GD55-LHPP effectively mediated LHPP expression in lung cancer cells. GD55-LHPP could effectively inhibit the proliferation of lung cancer cell lines and rarely affected normal cell growth. Mechanically, the oncolytic adenovirus GD55-LHPP was able to induce stronger apoptosis of lung cancer cells compared with GD55 through the activation of caspase signal pathway. Notably, GD55-LHPP also activated autophagy-related signal pathway. Further, GD55-LHPP efficiently inhibited tumor growth in lung cancer xenograft in mice and prolonged animal survival rate compared with the control GD55 or PBS. In conclusion, the novel construct GD55-LHPP provides a valuable strategy for lung cancer-targeted therapy and develop the role of tumor suppress gene LHPP in lung cancer gene therapy.


Assuntos
Adenoviridae , Apoptose , Neoplasias Pulmonares , Terapia Viral Oncolítica , Vírus Oncolíticos , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Humanos , Animais , Terapia Viral Oncolítica/métodos , Adenoviridae/genética , Vírus Oncolíticos/genética , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , Camundongos Nus , Feminino , Autofagia
14.
Pathol Res Pract ; 260: 155378, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38850880

RESUMO

Understanding the underlying mechanisms of breast cancer metastasis is of vital importance for developing treatment approaches. This review emphasizes contemporary breakthrough studies with special focus on breast cancer brain metastasis. Acquired mutational changes in metastatic lesions are often distinct from the primary tumor, suggesting altered mutagenesis pathways. The concept of micrometastases and heterogeneity within the tumors unravels novel therapeutic targets at genomic and molecular levels through epigenetic and proteomic profiling. Several pre-clinical studies have identified mechanisms involving the immune system, where tumor associated macrophages are key players. Expression of cell proteins like Syndecan1, fatty acid-binding protein 7 and tropomyosin kinase receptor B have been implicated in aiding the transmigration of breast cancer cells to the brain. Changes in the proteomic landscape of the blood-brain-barrier show altered permeability characteristics, supporting entry of cancer cells. Findings from laboratory studies pave the path for the emergence of new biomarkers, especially blood-based miRNA and circulating tumor cell markers for prognostic staging. The constantly evolving therapeutics call for clinical trials backing supportive evidence of efficacies of both novel and existing approaches. The challenge lying ahead is discovering innovative techniques to replace use of human samples and optimize small-scale patient recruitment in trials.

15.
Cell ; 187(12): 2969-2989.e24, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38776919

RESUMO

The gut fungal community represents an essential element of human health, yet its functional and metabolic potential remains insufficiently elucidated, largely due to the limited availability of reference genomes. To address this gap, we presented the cultivated gut fungi (CGF) catalog, encompassing 760 fungal genomes derived from the feces of healthy individuals. This catalog comprises 206 species spanning 48 families, including 69 species previously unidentified. We explored the functional and metabolic attributes of the CGF species and utilized this catalog to construct a phylogenetic representation of the gut mycobiome by analyzing over 11,000 fecal metagenomes from Chinese and non-Chinese populations. Moreover, we identified significant common disease-related variations in gut mycobiome composition and corroborated the associations between fungal signatures and inflammatory bowel disease (IBD) through animal experimentation. These resources and findings substantially enrich our understanding of the biological diversity and disease relevance of the human gut mycobiome.


Assuntos
Fungos , Microbioma Gastrointestinal , Micobioma , Animais , Humanos , Masculino , Camundongos , Fezes/microbiologia , Fungos/genética , Fungos/classificação , Fungos/isolamento & purificação , Genoma Fúngico/genética , Genômica , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/genética , Metagenoma , Filogenia , Feminino , Adulto , Pessoa de Meia-Idade
16.
iScience ; 27(6): 109902, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38812540

RESUMO

Patients with triple-negative breast cancer (TNBC) frequently experience resistance to chemotherapy, leading to recurrence. The approach of optimizing anti-tumoral immunological effect is promising in overcoming such resistance, given the heterogeneity and lack of biomarkers in TNBC. In this study, we focused on YTHDF2, an N6-methyladenosine (m6A) RNA-reader protein, in macrophages, one of the most abundant intra-tumoral immune cells. Using single-cell sequencing and ex vivo experiments, we discovered that YTHDF2 significantly promotes pro-tumoral phenotype polarization of macrophages and is closely associated with down-regulated antigen-presentation signaling to other immune cells in TNBC. The in vitro deprivation of YTHDF2 favors anti-tumoral effect. Expressions of multiple transcription factors, especially SPI1, were consistently observed in YTHDF2-high macrophages, providing potential therapeutic targets for new strategies. In conclusion, YTHDF2 in macrophages appears to promote pro-tumoral effects while suppressing immune activity, indicating the treatment targeting YTHDF2 or its transcription factors could be a promising strategy for chemoresistant TNBC.

17.
Micromachines (Basel) ; 15(5)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38793128

RESUMO

Continuous monitoring of vital signs based on advanced sensing technologies has attracted extensive attention due to the ravages of COVID-19. A maintenance-free and low-cost passive wireless sensing system based on surface acoustic wave (SAW) device can be used to continuously monitor temperature. However, the current SAW-based passive sensing system is mostly designed at a low frequency around 433 MHz, which leads to the relatively large size of SAW devices and antenna, hindering their application in wearable devices. In this paper, SAW devices with a resonant frequency distributed in the 870 MHz to 960 MHz range are rationally designed and fabricated. Based on the finite-element method (FEM) and coupling-of-modes (COM) model, the device parameters, including interdigital transducer (IDT) pairs, aperture size, and reflector pairs, are systematically optimized, and the theoretical and experimental results show high consistency. Finally, SAW temperature sensors with a quality factor greater than 2200 are obtained for real-time temperature monitoring ranging from 20 to 50 °C. Benefitting from the higher operating frequency, the size of the sensing system can be reduced for human body temperature monitoring, showing its potential to be used as a wearable monitoring device in the future.

18.
J Phys Chem Lett ; 15(22): 5848-5853, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38795047

RESUMO

Lead-free double perovskites offer enhanced stability and lower toxicity compared to their lead-based counterparts. Dual B-site cations can introduce elemental and structural diversity into double perovskite materials, enabling fine-tuning of the optical properties. However, the study of the nonlinear optical (NLO) properties of lead-free double perovskites is still nascent, hindering their relevant potential applications. Based on this, this work synthesizes a series of Cs2AgIn1-xBixCl6 (x = 0, 0.1, 0.25, 0.75, 1) single crystals, with the aim to explore the impact of composition on their NLO properties. Interestingly, Cs2AgInCl6 shows surface defect-induced second harmonic generation. With increasing Bi3+ concentration, the multiphoton absorption coefficients of Cs2AgIn1-xBixCl6 single crystals increase as a result of increasing state density. This work is helpful to understand well the NLO properties of lead-free double perovskites, laying a foundation for the development of related applications.

19.
Nature ; 630(8017): 695-703, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692285

RESUMO

The body-brain axis is emerging as a principal conductor of organismal physiology. It senses and controls organ function1,2, metabolism3 and nutritional state4-6. Here we show that a peripheral immune insult strongly activates the body-brain axis to regulate immune responses. We demonstrate that pro-inflammatory and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to inform the brain of an emerging inflammatory response. In turn, the brain tightly modulates the course of the peripheral immune response. Genetic silencing of this body-brain circuit produced unregulated and out-of-control inflammatory responses. By contrast, activating, rather than silencing, this circuit affords neural control of immune responses. We used single-cell RNA sequencing, combined with functional imaging, to identify the circuit components of this neuroimmune axis, and showed that its selective manipulation can effectively suppress the pro-inflammatory response while enhancing an anti-inflammatory state. The brain-evoked transformation of the course of an immune response offers new possibilities in the modulation of a wide range of immune disorders, from autoimmune diseases to cytokine storm and shock.


Assuntos
Encéfalo , Citocinas , Inflamação , Neuroimunomodulação , Animais , Feminino , Masculino , Camundongos , Encéfalo/citologia , Encéfalo/imunologia , Encéfalo/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Neuroimunomodulação/imunologia , Neuroimunomodulação/fisiologia , Neurônios/fisiologia , Nervo Vago/citologia , Nervo Vago/fisiologia , Análise da Expressão Gênica de Célula Única
20.
Bioorg Chem ; 148: 107491, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38788365

RESUMO

As a consequence of somatosensory nervous system injury or disease, neuropathic pain is commonly associated with chemotherapies, known as chemotherapy-induced peripheral neuropathy (CIPN). However, the mechanisms underlying CIPN-induced proteome aggregation in neuronal cells remain elusive due to limited detection tools. Herein, we present series sensors for fluorescence imaging (AggStain) and proteomics analysis (AggLink) to visualize and capture aggregated proteome in CIPN neuronal cell model. The environment-sensitive AggStain imaging sensor selectively binds and detects protein aggregation with 12.3 fold fluorescence enhancement. Further, the covalent AggLink proteomic sensor captures cellular aggregated proteins and profiles their composition via LC-MS/MS analysis. This integrative sensor platform reveals the presence of proteome aggregation in CIPN cell model and highlights its potential for broader applications in assessing proteome stability under various cellular stress conditions.


Assuntos
Antineoplásicos , Doenças do Sistema Nervoso Periférico , Proteoma , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/metabolismo , Humanos , Proteoma/análise , Proteoma/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Estrutura Molecular , Agregados Proteicos/efeitos dos fármacos , Imagem Óptica , Relação Dose-Resposta a Droga , Proteômica , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia
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