Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.966
Filtrar
1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 125036, 2025 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-39197210

RESUMO

Sodium tripolyphosphate (STPP), as one of the many food additives, can cause gastrointestinal discomfort and a variety of adverse reactions when ingested by the human body, which is a great potential threat to human health. Therefore, it is necessary to develop a fast, sensitive and simple method to detect STPP in food. In this study, we synthesized a kind of nitrogen-doped carbon quantum dots (N-CQDs), and were surprised to find that the addition of STPP led to the gradual enhancement of the emission peaks of the N-CQDs, with a good linearity in the range of 0.067-1.96 µM and a low detection limit as low as 0.024 µM. Up to now, there is no report on the use of carbon quantum dots for the direct detection of STPP. Meanwhile, we found that the addition of Al3+ effectively bursts the fluorescence intensity of N-CQDs@STPP solution and has a good linear relationship in the range of 0.33-6.25 µM with a lower detection limit of 0.24 µM. To this end, we developed a fluorescent probe to detect STPP and Al3+. In addition, the probe was successfully applied to the detection of bread samples, which has great potential for practical application.


Assuntos
Carbono , Corantes Fluorescentes , Aditivos Alimentares , Limite de Detecção , Polifosfatos , Pontos Quânticos , Espectrometria de Fluorescência , Pontos Quânticos/química , Corantes Fluorescentes/química , Aditivos Alimentares/análise , Espectrometria de Fluorescência/métodos , Carbono/química , Polifosfatos/análise , Polifosfatos/química , Alumínio/análise , Nitrogênio/química , Pão/análise
2.
J Colloid Interface Sci ; 677(Pt A): 346-358, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39096703

RESUMO

HYPOTHESIS: Hexavalent chromium, recognized as one of the most toxic heavy metals, demands the development of advanced materials capable of both adsorption and photocatalysis for effective Cr (VI) removal. EXPERIMENTS: This study successfully synthesized a two-dimensional zinc porphyrin covalent organic framework (ZnPor-COF) via a solvent-based method. Performance evaluations have demonstrated that the ZnPor-COF possesses outstanding capabilities for the adsorptive and/or photocatalytic elimination of Cr (VI). Particularly noteworthy is the observation that when adsorption and photocatalysis are coupled, the ZnPor-COF attains an exceptional 99.7 % removal rate for a Cr (VI) concentration of 30 mg/L within just 60 min, with minimal susceptibility to coexisting ions. After five consecutive cycles, the material sustains a removal efficiency of 90 %, indicative of its robust cyclability. FINDINGS: Theoretical calculations, as well as experimental validations, have indicated that the integration of Zn ions into the porphyrin COF not only results in an expanded specific surface area and an increased count of adsorption sites but also significantly improves the COF's photosensitivity and the capability for charge carrier separation. Furthermore, the core of the synergistic effect between adsorption and photocatalysis lies in the ability of photocatalysis to substantially augment the adsorption process.

3.
Adv Mater ; : e2412541, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350447

RESUMO

Chemical synthesis of unconventional topologically close-packed intermetallic nanocrystals (NCs) remains a considerable challenge due to the limitation of large volume asymmetry between the components. Here, a series of unconventional intermetallic Frank-Kasper C15 phase Ir2M (M = rare earth metals La, Ce, Gd, Tb, Tm) NCs is successfully prepared via a molten-salt assisted reduction method as efficient electrocatalysts for hydrogen evolution reaction (HER). Compared to the disordered counterpart (A1-Ir2Ce), C15-Ir2Ce features higher Ir-Ce coordination number that leads to an electron-rich environment for Ir sites. The C15-Ir2Ce catalyst exhibits excellent and pH-universal HER activity and requires only 9, 16, and 27 mV overpotentials to attain 10 mA cm-2 in acidic, alkaline, and neutral electrolytes, respectively, representing one of the best HER electrocatalysts ever reported. In a proton exchange membrane water electrolyzer, the C15-Ir2Ce cathode achieves an industrial-scale current density of 1 A cm-2 with a remarkably low cell voltage of 1.7 V at 80 °C and can operate stably for 1000 h with a sluggish voltage decay rate of 50 µV h-1. Theoretical investigations reveal that the electron-rich Ir sites intensify the polarization of *H2O intermediate on C15-Ir2Ce, thus lowering the energy barrier of the water dissociation and facilitating the HER kinetics.

4.
Clin Transl Med ; 14(10): e70036, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39350478

RESUMO

Solid tumours exhibit a well-defined architecture, comprising a differentiated core and a dynamic border that interfaces with the surrounding tissue. This border, characterised by distinct cellular morphology and molecular composition, serves as a critical determinant of the tumour's invasive behaviour. Notably, the invasive border of the primary tumour represents the principal site for intravasation of metastatic cells. These cells, known as circulating tumour cells (CTCs), function as 'seeds' for distant dissemination and display remarkable heterogeneity. Advancements in spatial sequencing technology are progressively unveiling the spatial biological features of tumours. However, systematic investigations specifically targeting the characteristics of the tumour border remain scarce. In this comprehensive review, we illuminate key biological insights along the tumour body-border-haematogenous metastasis axis over the past five years. We delineate the distinctive landscape of tumour invasion boundaries and delve into the intricate heterogeneity and phenotype of CTCs, which orchestrate haematogenous metastasis. These insights have the potential to explain the basis of tumour invasion and distant metastasis, offering new perspectives for the development of more complex and precise clinical interventions and treatments.


Assuntos
Invasividade Neoplásica , Metástase Neoplásica , Células Neoplásicas Circulantes , Análise de Célula Única , Humanos , Metástase Neoplásica/genética , Análise de Célula Única/métodos , Invasividade Neoplásica/genética , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/genética
6.
Hemasphere ; 8(10): e70007, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39380843

RESUMO

Severe cytokine release syndrome (sCRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have limited the widespread use of chimeric antigen receptor T (CAR T)-cell therapy. We designed a novel anti-CD19 CAR (ssCART-19) with a small hairpin RNA (shRNA) element to silence the interleukin-6 (IL-6) gene, hypothesizing it could reduce sCRS and ICANS by alleviating monocyte activation and proinflammatory cytokine release. In a post hoc analysis of two clinical trials, we compared ssCART-19 with common CAR T-cells (cCART-19) in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Among 87 patients, 47 received ssCART-19 and 40 received cCART-19. Grade ≥3 CRS occurred in 14.89% (7/47) of the ssCART-19 group versus 37.5% (15/40) in the cCART-19 group (p = 0.036). ICANS occurred in 4.26% (2/47) of the ssCART-19 group (all grade 1) compared to 15% (2/40) of the cCART-19 group. Patients in the ssCART-19 group showed comparable rates of treatment response (calculated with rates of complete remission and incomplete hematological recovery) were 91.49% (43/47) for ssCART-19 and 85% (34/40) for cCART-19 (p = 0.999). With a median follow-up of 21.9 months, cumulative nonrelapse mortality was 10.4% for ssCART-19 and 13.6% for cCART-19 (p = 0.33). Median overall survival was 37.17 months for ssCART-19 and 32.93 months for cCART-19 (p = 0.40). Median progression-free survival was 24.17 months for ssCART-19 and 9.33 months for cCART-19 (p = 0.23). These data support the safety and efficacy of ssCART-19 for r/r B-ALL, suggesting its potential as a promising therapy.

7.
Cardiology ; : 1-26, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39383845

RESUMO

INTRODUCTION: The effect of T lymphocytes on atrial fibrillation (AF) is still unclear. We aimed to assess the associations between the T lymphocyte subgroup distribution and incident AF and AF prognosis. METHODS: Consecutive patients were enrolled from June 2020 to October 2021. Their T-cell subgroups, including CD3, CD4, and CD8 T cells, and the CD4/CD8 ratio (CDR) were measured. We assessed the relationships between the CDR and composite endpoints, including hospitalization due to heart failure, stroke or systemic embolism, and cardiovascular mortality rates. RESULTS: A total of 45905 patients, among whom 818 had AF, were enrolled. The proportions of the T lymphocyte subgroups CD3 (OR 0.9995; 95% CI 0.9993-0.9997, P < 0.001), CD4 (OR 0.9995; 95% CI 0.9991-0.9998, P = 0.004), and CD8 (OR 0.9988; 95% CI 0.9984-0.9992, P < 0.001) and the CDR (OR 1.2714; 95% CI 1.1355-1.4165, P < 0.001) were correlated with AF incidence. The CDR was associated with AF incidence (OR 1.1998; 95% CI 1.0746-1.3336, P<0.001) after adjustment. High CDR was associated with a higher rate of hospitalization due to heart failure (HR 3.45; 95% CI 1.71-6.96, P < 0.001), stroke or systemic embolism (HR 2.54; 95% CI 1.32-4.91, P = 0.005), and cardiovascular mortality (HR 2.25; 95% CI 1.05-4.84, P = 0.038). There was no significant difference in all-cause mortality between CDR strata (HR 1.61; 95% CI 0.90-2.87, P = 0.111). CONCLUSION: Elevated CDR was positively associated with the incidence and prognosis of AF. This finding may help improve the prevention and treatment of AF.

8.
Front Psychiatry ; 15: 1428425, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39371911

RESUMO

Background: Major depressive disorder (MDD) is associated with deficits in cognitive function, thought to be related to underlying decreased hedonic experiences. Further research is needed to fully elucidate the role of functional brain activity in this relationship. In this study, we investigated the neurofunctional correlate of the interplay between cognitive function and hedonic experiences in medication-free MDD using functional near-infrared spectroscopy (fNIRS). Methods: We examine differences of brain activation corresponding to the verbal fluency test (VFT) between MDD patients and healthy controls (HCs). Fifty-six MDD patients and 35 HCs underwent fMRI scanning while performing the VFT. In exploratory analyses, cognitive performance, as assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB), four dimensions of hedonic processing (desire, motivation, effort, and consummatory pleasure) measured by the Dimensional Anhedonia Rating Scale (DARS), and relative changes in oxygenated hemoglobin concentration during the VFT were compared across groups. Results: Patients with MDD demonstrated impairments in sustained attention and working memory, accompanied by lower total and subscale scores on the DARS. Compared to healthy controls, MDD patients exhibited reduced activation in the prefrontal cortex (PFC) during the VFT task (t = 2.32 to 4.77, p < 0.001 to 0.02, FDR corrected). DARS motivation, desire, and total scores as well as sustained attention, were positively correlated with activation in the dorsolateral PFC and Broca's area (p < 0.05, FDR corrected). Conclusions: These findings indicate that changes in prefrontal lobe oxygenated hemoglobin levels, a region implicated in hedonic motivation and cognitive function, may serve as potential biomarkers for interventions targeting individuals with MDD. Our results corroborate the clinical consensus that the prefrontal cortex is a primary target for non-invasive neuromodulatory treatments for depression.

9.
Vox Sang ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39374941

RESUMO

BACKGROUND AND OBJECTIVES: Accurate human leucocyte antigen (HLA) and human platelet antigen (HPA) typing is essential for establishing a blood platelet donor bank to deal with refractoriness in patients undergoing multiple platelet transfusions. Current methods, such as Sanger and next-generation sequencing, encounter difficulties in haplotyping. Herein, the aim of this study was to establish a method for HLA and HPA typing based on the long read sequencing. STUDY DESIGN AND METHODS: The HPA and HLA class I genotypes of 268 platelet donors from the Taiyuan Blood Center, China were identified using long-read sequencing on the PacBio platform. Allele frequencies for HPA systems and HLA class I genes were calculated, and genetic variability within HPA system genes was analysed. RESULTS: Polymorphisms were identified in 8 of the 35 HPA systems (HPA-1 to HPA-6w, HPA-15 and HPA-21w), with the frequencies of the 'b' allele at 0.0187, 0.0709, 0.4086, 0.0075, 0.0149, 0.0317, 0.4310 and 0.0019, respectively. The alleles with the highest frequencies at the HLA-A, HLA-B and HLA-C loci are HLA-A02:01, B51:01, B46:01 and C06:02, respectively. Additionally, several genetic patterns in HPA systems were identified, including the c.166-1029C>T variant, which was found exclusively in samples carrying the HPA-1b allele. CONCLUSION: This study developed a targeted long-read sequencing method characterized by high throughput and simultaneity, capable of resolving allele ambiguities for effective HLA class I genotyping in establishing a platelet donor bank.

10.
Heliyon ; 10(19): e38147, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39386840

RESUMO

Background: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and everolimus (EVE) are effective for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). However, the efficacy of different sequences of CDK4/6i and EVE are largely unknown. The study aimed to explore the efficacy of different sequences in China. Methods: 146 patients with HR+/HER2- MBC who received both CDK4/6i and EVE in salvage setting were collected. Objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS) were investigated. Results: 56 patients received CDK4/6i prior to EVE (Group A), 90 patients received CDK4/6i subsequent to EVE (Group B). The median PFS of CDK4/6i and EVE in Group A vs Group B were 8.4m and 2.5m vs 4.6m and 6.1m respectively. The total PFS of first-line and second-line endocrine therapy were not different between Group A and Group B [13.1m vs 17.7m (P = 0.330, HR = 0.738, 95%CI: 0.399-1.365)]. The 5y OS of patients in Group A or Group B were 62.0 % vs 57.4 %, P = 0.569. Conclusions: We found that no matter CDK4/6i or EVE was used first, the survival were not significantly different between Group A and Group B. Both can be clinical options.

11.
Cell Rep ; 43(10): 114818, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39388353

RESUMO

Selective serotonin reuptake inhibitors (SSRIs) have shown promise in cancer therapy, particularly for hepatocellular carcinoma (HCC), but their molecular targets and mechanisms remain unclear. Here, we show that SSRIs exhibit significant anti-HCC effects independent of their classical target, the serotonin reuptake transporter (SERT). Using global inverse gene expression profiling, drug affinity responsive target stability assays, and in silico molecular docking, we demonstrate that citalopram targets glucose transporter 1 (GLUT1), resulting in reduced glycolytic flux. A mutant GLUT1 variant at the citalopram binding site (E380) diminishes the drug's inhibitory effects on the Warburg effect and tumor growth. In preclinical models, citalopram dampens the growth of GLUT1high liver tumors and displays a synergistic effect with anti-PD-1 therapy. Retrospective analysis reveals that SSRI use correlates with a lower risk of metastasis among patients with HCC. Our study describes a role for SSRIs in cancer metabolism, establishing a rationale for their repurposing as potential anti-cancer drugs for HCC.

12.
Public Health ; 237: 141-146, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39388733

RESUMO

OBJECTIVES: Understanding the burden of influenza-associated acute respiratory infection (ARI) and severe ARI (SARI) is crucial for public health decision-making. A population-based study with multiple data sources was conducted to estimate the burden of influenza-associated ARI in Wanzhou District, Chongqing, southern China. STUDY DESIGN: Population-based surveillance study. METHODS: Active surveillance of ARI was conducted in different levels of health facilities in the Wanzhou District between October 2021 and March 2022. Nasal or throat swabs were collected and tested for influenza viruses in hospital-based surveillance. A health utilisation survey was used to estimate health-seeking behaviour, and all electronic medical records were collected. An epidemiological model was used to estimate the disease burden. RESULTS: There were an estimated 52,960 influenza-associated ARI (95 % confidence interval [CI]: 39,213-84,891), including 2,529 SARI cases (95 % CI: 1,385-21,712) during winter 2021/22 in the Wanzhou District. The incidence rate for all influenza-associated ARI and SARI was 3,385/100,000 and 162/100,000, respectively. A higher incidence rate of influenza-associated ARI was observed among individuals aged <50 years, while a higher influenza-associated SARI rate was observed in those aged ≥50 years. CONCLUSIONS: Using an epidemiological model with data from multiple sources, this study documented a substantial burden of influenza-associated ARI in the Wanzhou District, highlighting the need for influenza vaccination and providing a possible foundation for public health decision-making.

13.
Adv Mater ; : e2407150, 2024 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-39370569

RESUMO

The development of new ionic conductors meeting the requirements of current solid-state devices is imminent but still challenging. Hydrogen-bonded ionic co-crystals (HICs) are multi-component crystals based on hydrogen bonding and Coulombic interactions. Due to the hydrogen bond network and unique features of ionic crystals, HICs have flexible skeletons. More importantly, anion vacancies on their surface can potentially help dissociate and adsorb excess anions, forming cation transport channels at grain boundaries. Here, it is demonstrated that a HIC optimized by adjusting the ratio of zinc salt and imidazole can construct grain boundary-based fast Zn2+ transport channels. The as-obtained HIC solid electrolyte possesses an unprecedentedly high ionic conductivity at room and low temperatures (≈11.2 mS cm-1 at 25 °C and ≈2.78 mS cm-1 at -40 °C) with ultra-low activation energy (≈0.12 eV), while restraining dendrite growth and exhibiting low overpotential even at a high current density (<200 mV at 5.0 mA cm-2) during Zn symmetric cell cycling. This HIC also allows solid-state Zn||covalent organic framework full cells to work at low temperatures, providing superior stability. More importantly, the HIC can even support zinc-ion hybrid supercapacitors to work, achieving extraordinary rate capability and a power density comparable to aqueous solution-based supercapacitors. This work provides a path for designing facilely prepared, low-cost, and environmentally friendly ionic conductors with extremely high ionic conductivity and excellent interface compatibility.

14.
J Colloid Interface Sci ; 679(Pt A): 253-261, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39362150

RESUMO

Developing a highly active and stable non-precious metal catalyst for oxygen reduction reaction (ORR) is of great practical significance for advancing fuel cell technology. In this work, a continuous two-step hydrothermal reaction followed by high temperature pyrolysis were employed to achieve in situ N-doping preferentially into Ketjenblack carbon (KB-N) and composite of KB-N and Co/CoxOy nanofilms (Co/CoxOy-NFs) as Co/CoxOy-NFs@KB-N. The N-doped state strongly affects the ORR activity of catalyst. All prepared Co/CoxOy-NFs@KB-N catalysts exhibit observably improved ORR activity compared with the basal KB-N and N-doped Co/CoxOy-NFs, in which the optimal Co/CoxOy-NFs@KB-N catalyst demonstrate the positive Eonset (0.864 V) and E1/2 (0.788 V) vs. RHE, the low Tafel slope (69.27 mV dec-1), implying quick ORR kinetics. And, the Co/CoxOy-NFs@KB-N catalyst exhibits highly electrochemical durability. The KB-N substrate can purify Co valence in CoO component, promote amorphization of CoO crystalline structure and enhance the interaction between Co/CoxOy-NFs and KB-N in Co/CoxOy-NFs@KB-N catalyst. Thus electronic effect, structural effect and synergistic effect can strengthen O2 adsorption, provide enough adsorbed sites and accelerate electron transfer, resulting in prominent ORR performance of Co/CoxOy-NFs@KB-N catalyst.

15.
Acta Biomater ; 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39362448

RESUMO

Understanding matrix molecular activities that regulate the postnatal growth and remodeling of temporomandibular joint (TMJ) condylar cartilage and articular disc will enable the development of effective regenerative strategies targeting TMJ disorder. This study elucidated the distinct roles of type V collagen (collagen V) in regulating these two units. Studying the TMJ of young adult Col5a1+/- mice, we found loss of collagen V resulted in substantial changes in the proliferation, clustering, and density of progenitors in condylar cartilage, but did not have a major impact on disc cells that are more fibroblast-like. Although loss of collagen V led to thickened collagen fibrils with increased heterogeneity in the disc, there were no significant changes in local micromodulus except for a reduction at the posterior end of the inferior side. Following the induction of aberrant occlusal loading by the unilateral anterior crossbite (UAC) procedure, both wild-type (WT) and Col5a1+/- condylar cartilage exhibited salient remodeling, and Col5a1+/- condyle developed more pronounced degeneration and hypertrophy at the posterior end than the WT. In contrast, neither UAC nor collagen V deficiency induced marked changes in the morphology or mechanical properties of the disc. Together, our findings highlight the distinct roles of collagen V in regulating these two units during postnatal growth and remodeling, emphasizing its more crucial role in condylar cartilage due to its impact on the highly mechanosensitive progenitors. Results thus provide the foundation for using collagen V to improve the regeneration of TMJ and the care of patients with TMJ disorder. STATEMENT OF SIGNIFICANCE: Successful regeneration of temporomandibular joint (TMJ) condylar cartilage and articular disc remains a significant challenge due to the limited understanding of matrix molecular activities that regulate the formation and remodeling of these tissues. This study demonstrates that collagen V plays distinct and critical roles in these processes. In condylar cartilage, collagen V is essential for regulating progenitor cell fate and maintaining matrix integrity. In the disc, collagen V also regulates fibril structure and local micromechanics, but has a limited impact on cell phenotype or its remodeling response. Our findings establish collagen V as a key component in maintaining the integrity of these two units, with a more crucial role in condylar cartilage due to its impact on progenitor cell activities.

16.
Orphanet J Rare Dis ; 19(1): 371, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39380097

RESUMO

Phenotypes play a fundamental role in medical genetics, serving as external manifestations of underlying genotypes. Deep phenotyping, a cornerstone of precision medicine, involves precise multi-system phenotype assessments, facilitating disease subtyping and genetic understanding. Despite their significance, the field lacks standardized protocols for accurate phenotype evaluation, hindering clinical comprehension and research comparability. We present a comprehensive workflow of deep phenotyping for rare bone diseases from the Genetics Clinic of Skeletal Deformity at Peking Union Medical College Hospital. Our workflow integrates referral, informed consent, and detailed phenotype evaluation through HPO standards, capturing nuanced phenotypic characteristics using clinical examinations, questionnaires, and multimedia documentation. Genetic testing and counseling follow, based on deep phenotyping results, ensuring personalized interventions. Multidisciplinary team consultations facilitate comprehensive patient care and clinical guideline development. Regular follow-up visits emphasize dynamic phenotype reassessment, ensuring treatment strategies remain responsive to evolving patient needs. In conclusion, this study highlights the importance of deep phenotyping in rare bone diseases, offering a standardized framework for phenotype evaluation, genetic analysis, and multidisciplinary intervention. By enhancing clinical care and research outcomes, this approach contributes to the advancement of precision medicine in the field of medical genetics.


Assuntos
Doenças Ósseas , Fenótipo , Doenças Raras , Humanos , Doenças Raras/genética , Doenças Raras/diagnóstico , Doenças Ósseas/genética , Doenças Ósseas/diagnóstico , Doenças Ósseas/terapia , Testes Genéticos/métodos , Medicina de Precisão/métodos , Fluxo de Trabalho , Feminino , Masculino
17.
Signal Transduct Target Ther ; 9(1): 266, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39370455

RESUMO

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Its complexity is influenced by various signal transduction networks that govern cellular proliferation, survival, differentiation, and apoptosis. The pathogenesis of CRC is a testament to the dysregulation of these signaling cascades, which culminates in the malignant transformation of colonic epithelium. This review aims to dissect the foundational signaling mechanisms implicated in CRC, to elucidate the generalized principles underpinning neoplastic evolution and progression. We discuss the molecular hallmarks of CRC, including the genomic, epigenomic and microbial features of CRC to highlight the role of signal transduction in the orchestration of the tumorigenic process. Concurrently, we review the advent of targeted and immune therapies in CRC, assessing their impact on the current clinical landscape. The development of these therapies has been informed by a deepening understanding of oncogenic signaling, leading to the identification of key nodes within these networks that can be exploited pharmacologically. Furthermore, we explore the potential of integrating AI to enhance the precision of therapeutic targeting and patient stratification, emphasizing their role in personalized medicine. In summary, our review captures the dynamic interplay between aberrant signaling in CRC pathogenesis and the concerted efforts to counteract these changes through targeted therapeutic strategies, ultimately aiming to pave the way for improved prognosis and personalized treatment modalities in colorectal cancer.


Assuntos
Neoplasias Colorretais , Transdução de Sinais , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Terapia de Alvo Molecular , Medicina de Precisão
18.
Comput Biol Med ; 183: 109237, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39378581

RESUMO

Ensuring accurate predictions of inpatient length of stay (LoS) and mortality rates is essential for enhancing hospital service efficiency, particularly in light of the constraints posed by limited healthcare resources. Integrative analysis of heterogeneous clinic record data from different sources can hold great promise for improving the prognosis and diagnosis level of LoS and mortality. Currently, most existing studies solely focus on single data modality or tend to single-task learning, i.e., training LoS and mortality tasks separately. This limits the utilization of available multi-modal data and prevents the sharing of feature representations that could capture correlations between different tasks, ultimately hindering the model's performance. To address the challenge, this study proposes a novel Multi-Modal Multi-Task learning model, termed as M3T-LM, to integrate clinic records to predict inpatients' LoS and mortality simultaneously. The M3T-LM framework incorporates multiple data modalities by constructing sub-models tailored to each modality. Specifically, a novel attention-embedded one-dimensional (1D) convolutional neural network (CNN) is designed to handle numerical data. For clinical notes, they are converted into sequence data, and then two long short-term memory (LSTM) networks are exploited to model on textual sequence data. A two-dimensional (2D) CNN architecture, noted as CRXMDL, is designed to extract high-level features from chest X-ray (CXR) images. Subsequently, multiple sub-models are integrated to formulate the M3T-LM to capture the correlations between patient LoS and modality prediction tasks. The efficiency of the proposed method is validated on the MIMIC-IV dataset. The proposed method attained a test MAE of 5.54 for LoS prediction and a test F1 of 0.876 for mortality prediction. The experimental results demonstrate that our approach outperforms state-of-the-art (SOTA) methods in tackling mixed regression and classification tasks.

19.
J Colloid Interface Sci ; 679(Pt A): 296-306, 2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39366259

RESUMO

The oxygen evolution reaction (OER) at the anode undergoes a sluggish multi-step process, thereby impeding overall water splitting. As the classical adsorbate evolution mechanism (AEM) involves multiple oxygen-containing intermediates, such as *OH, *O and *OOH, breaking the linear relationship of the adsorption energies between *OH and *OOH is the key to efficient oxygen evolution. Herein, we report a high-entropy FeCoNiAlZn layered double hydroxide decorated with defects (E-FeCoNiAlZn LDH) for boosting oxygen evolution in alkaline. The product exhibits high OER activity with a low overpotential of 220 at 10 mA cm-2 and outstanding stability with negligible decline after 100 h operation. The defects in E-FeCoNiAlZn LDH not only enhance the adsorption of *OH by metal sites but also foster the release of oxygen from lattice, which triggers the coupled oxygen evolution mechanism (COM). This mechanism has only *OH and *OO intermediates, perfectly avoiding the obstacles of linear relationship between *OH and *OOH. Theoretical calculations demonstrate that the introduction of defects enhances the adsorption of *OH due to the presence of unsaturated bonds. Additionally, it is evidence that the O 2p band is elevated, leading to a weakening of the metal-O bond and a reduction of the energy barrier for OO coupling.

20.
J Affect Disord ; 369: 508-515, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39393462

RESUMO

BACKGROUND: The evidence for an association between early menarche and depression is inconsistent. We therefore performed a meta-analysis to examine this association. METHODS: The protocol for the current study was registered at the International Prospective Register of Systematic Reviews (PROSPERO) with registration number CRD42023483591. We searched several databases up to 17 June 2024. Random effects models were used to calculate pooled effect sizes. RESULTS: A total of 22 studies involving 87,798 participants were included. The Newcastle-Ottawa Scale (NOS) scores of the 22 studies ranged from 4 to 8, with a median score of 6. Depression scores and depression incidence were significantly higher in the early menarche group than in the non-early menarche group (Standardized Mean Difference: 0.13, 95 % CI: 0.04, 0.21; OR: 1.37, 95 % CI: 1.23, 1.52). However, moderate heterogeneity was observed (depression scores: I2 = 54 %, p = 0.03; depression incidence: I2 = 61 %, p = 0.001). Subgroup analyses revealed that depression scores were significantly associated with study type (cohort studies: I2 = 57 %, p = 0.071; case-control studies: I2 = 61 %, p = 0.051) and study quality (≥ 6: I2 = 58 %, p = 0.065; < 6: I2 = 62 %, p = 0.052). CONCLUSIONS: This meta-analysis revealed that early menarche was associated with depression. Parents, schools and health care providers should monitor the emotions of girls who experience menarche at an earlier age.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA