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1.
Bioresour Technol ; : 130893, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38795923

RESUMEN

This study investigated the performance of combined nanobubble water (NW) and digestate in the soaking hydrolysis process. Two types of NW (CO2NW and O2NW) with digestate were used to soak rice straw for 1, 2, 3, 5, and 7 days. During soaking process, the volatile fatty acids (VFA) concentration in the treatment with O2NW and digestate for 3 days (O2NW-3 d) reached 7179.5 mg-HAc/L. Moreover, the highest specific methane yield (SMY) obtained in this treatment could reach 336.7 NmL/gVS. Although the addition of NW did not significantly increase SMY from digestate soaking, NW could accelerate the rate of methane production and reduce digestion time of T80. The enrichment of Enterobacter in the soaking process was observed when using CO2NW and O2NW as soaking solutions which played important roles in VFA production. This study provides a new insight into environment-friendly enhanced crop straw pretreatment, combining NW and digestate soaking hydrolysis.

2.
Chin J Integr Med ; 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38816637

RESUMEN

The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets.

3.
Sci Technol Adv Mater ; 25(1): 2346067, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38817249

RESUMEN

Wire-feed additive manufacturing (WFAM) produces superalloys with complex thermal cycles and unique microstructures, often requiring optimized heat treatments. To address this challenge, we present a hybrid approach that combines high-throughput experiments, precipitation simulation, and machine learning to design effective aging conditions for the WFAM Haynes 282 superalloy. Our results demonstrate that the γ' radius is the critical microstructural feature for strengthening Haynes 282 during post-heat treatment compared with the matrix composition and γ' volume fraction. New aging conditions at 770°C for 50 hours and 730°C for 200 hours were discovered based on the machine learning model and were applied to enhance yield strength, bringing it on par with the wrought counterpart. This approach has significant implications for future AM alloy production, enabling more efficient and effective heat treatment design to achieve desired properties.


Our research tackles suboptimal properties in additively manufactured alloys with conventional heat treatment, using high-throughput experiments, CALPHAD (CALculation of PHAse Diagrams), and interpretable machine learning to effectively optimize heat treatments for WFAM (Wire-Feed Additive Manufacturing) Haynes 282 superalloy.

4.
J Exp Clin Cancer Res ; 43(1): 152, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38812060

RESUMEN

BACKGROUND: Intrahepatic cholangiocarcinoma (ICCA) is a heterogeneous group of malignant tumors characterized by high recurrence rate and poor prognosis. Heterochromatin Protein 1α (HP1α) is one of the most important nonhistone chromosomal proteins involved in transcriptional silencing via heterochromatin formation and structural maintenance. The effect of HP1α on the progression of ICCA remained unclear. METHODS: The effect on the proliferation of ICCA was detected by experiments in two cell lines and two ICCA mouse models. The interaction between HP1α and Histone Deacetylase 1 (HDAC1) was determined using Electrospray Ionization Mass Spectrometry (ESI-MS) and the binding mechanism was studied using immunoprecipitation assays (co-IP). The target gene was screened out by RNA sequencing (RNA-seq). The occupation of DNA binding proteins and histone modifications were predicted by bioinformatic methods and evaluated by Cleavage Under Targets and Tagmentation (CUT & Tag) and Chromatin immunoprecipitation (ChIP). RESULTS: HP1α was upregulated in intrahepatic cholangiocarcinoma (ICCA) tissues and regulated the proliferation of ICCA cells by inhibiting the interferon pathway in a Signal Transducer and Activator of Transcription 1 (STAT1)-dependent manner. Mechanistically, STAT1 is transcriptionally regulated by the HP1α-HDAC1 complex directly and epigenetically via promoter binding and changes in different histone modifications, as validated by high-throughput sequencing. Broad-spectrum HDAC inhibitor (HDACi) activates the interferon pathway and inhibits the proliferation of ICCA cells by downregulating HP1α and targeting the heterodimer. Broad-spectrum HDACi plus interferon preparation regimen was found to improve the antiproliferative effects and delay ICCA development in vivo and in vitro, which took advantage of basal activation as well as direct activation of the interferon pathway. HP1α participates in mediating the cellular resistance to both agents. CONCLUSIONS: HP1α-HDAC1 complex influences interferon pathway activation by directly and epigenetically regulating STAT1 in transcriptional level. The broad-spectrum HDACi plus interferon preparation regimen inhibits ICCA development, providing feasible strategies for ICCA treatment. Targeting the HP1α-HDAC1-STAT1 axis is a possible strategy for treating ICCA, especially HP1α-positive cases.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Homólogo de la Proteína Chromobox 5 , Histona Desacetilasa 1 , Factor de Transcripción STAT1 , Colangiocarcinoma/metabolismo , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Colangiocarcinoma/genética , Humanos , Homólogo de la Proteína Chromobox 5/metabolismo , Histona Desacetilasa 1/metabolismo , Ratones , Animales , Factor de Transcripción STAT1/metabolismo , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/genética , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Línea Celular Tumoral , Proliferación Celular , Masculino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Femenino
5.
Mol Biol Rep ; 51(1): 648, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38727802

RESUMEN

BACKGROUND: Polygonatum kingianum holds significant importance in Traditional Chinese Medicine due to its medicinal properties, characterized by its diverse chemical constituents including polysaccharides, terpenoids, flavonoids, phenols, and phenylpropanoids. The Auxin Response Factor (ARF) is a pivotal transcription factor known for its regulatory role in both primary and secondary metabolite synthesis. However, our understanding of the ARF gene family in P. kingianum remains limited. METHODS AND RESULTS: We employed RNA-Seq to sequence three distinct tissues (leaf, root, and stem) of P. kingianum. The analysis revealed a total of 31,558 differentially expressed genes (DEGs), with 43 species of transcription factors annotated among them. Analyses via gene ontology and the Kyoto Encyclopedia of Genes and Genomes demonstrated that these DEGs were predominantly enriched in metabolic pathways and secondary metabolite biosynthesis. The proposed temporal expression analysis categorized the DEGs into nine clusters, suggesting the same expression trends that may be coordinated in multiple biological processes across the three tissues. Additionally, we conducted screening and expression pattern analysis of the ARF gene family, identifying 12 significantly expressed PkARF genes in P. kingianum roots. This discovery lays the groundwork for investigations into the role of PkARF genes in root growth, development, and secondary metabolism regulation. CONCLUSION: The obtained data and insights serve as a focal point for further research studies, centred on genetic manipulation of growth and secondary metabolism in P. kingianum. Furthermore, these findings contribute to the understanding of functional genomics in P. kingianum, offering valuable genetic resources.


Asunto(s)
Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Proteínas de Plantas , Plantas Medicinales , Polygonatum , Transcriptoma , Plantas Medicinales/genética , Plantas Medicinales/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Polygonatum/genética , Polygonatum/metabolismo , Transcriptoma/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilación de la Expresión Génica/métodos , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ontología de Genes , Hojas de la Planta/genética , Hojas de la Planta/metabolismo
6.
Angew Chem Int Ed Engl ; : e202405123, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714495

RESUMEN

In this work, we investigate trion dynamics occurring at the heterojunction between organometallic molecules and a monolayer transition metal dichalcogenide (TMD) with transient electronic sum frequency generation (tr-ESFG) spectroscopy. By pumping at 2.4 eV with laser pulses, we have observed an ultrafast hole transfer, succeeded by the emergence of charge-transfer trions. This observation is facilitated by the cancellation of ground state bleach and stimulated emission signals due to their opposite phases, making tr-ESFG especially sensitive to the trion formation dynamics. The presence of charge-transfer trion at molecular functionalized TMD monolayers suggests the potential for engineering the local electronic structures and dynamics of specific locations on TMDs and offers the potential for transferring unique electronic attributes of TMD to the molecular layers.

7.
Adv Sci (Weinh) ; : e2401394, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38715382

RESUMEN

Currently, the typical combination therapy of programmed death ligand-1 (PD-L1) antibodies with radiotherapy (RT) still exhibits impaired immunogenic antitumor response in clinical due to lessened DNA damage and acquired immune tolerance via the upregulation of some other immune checkpoint inhibitors. Apart from this, such combination therapy may raise the occurrence rate of radiation-induced lung fibrosis (RIPF) due to enhanced systemic inflammation, leading to the ultimate death of cancer patients (average survival time of about 3 years). Therefore, it is newly revealed that mitochondria energy metabolism regulation can be used as a novel effective PD-L1 and transforming growth factor-ß (TGF-ß) dual-downregulation method. Following this, IR-TAM is prepared by conjugating mitochondria-targeted heptamethine cyanine dye IR-68 with oxidative phosphorylation (OXPHOS) inhibitor Tamoxifen (TAM), which then self-assembled with albumin (Alb) to form IR-TAM@Alb nanoparticles. By doing this, tumor-targeting IR-TAM@Alb nanoparticle effectively reversed tumor hypoxia and depressed PD-L1 and TGF-ß expression to sensitize RT. Meanwhile, due to the capacity of heptamethine cyanine dye in targeting RIPF and the function of TAM in depressing TGF-ß, IR-TAM@Alb also ameliorated fibrosis development induced by RT.

8.
Adv Sci (Weinh) ; : e2400297, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38704675

RESUMEN

It is newly revealed that collagen works as a physical barrier to tumor immune infiltration, oxygen perfusion, and immune depressor in solid tumors. Meanwhile, after radiotherapy (RT), the programmed death ligand-1 (PD-L1) overexpression and transforming growth factor-ß (TGF-ß) excessive secretion would accelerate DNA damage repair and trigger T cell exclusion to limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective RT simultaneously, effectively, and easily. In this study, it is revealed that inducing mitochondria dysfunction by using oxidative phosphorylation inhibitors like Lonidamine (LND) can serve as a highly effective multi-immune pathway regulation strategy through PD-L1, collagen, and TGF-ß co-depression. Then, IR-LND is prepared by combining the mitochondria-targeted molecule IR-68 with LND, which then is loaded with liposomes (Lip) to create IR-LND@Lip nanoadjuvants. By doing this, IR-LND@Lip more effectively sensitizes RT by generating more DNA damage and transforming cold tumors into hot ones through immune activation by PD-L1, collagen, and TGF-ß co-inhibition. In conclusion, the combined treatment of RT and IR-LND@Lip ultimately almost completely suppressed the growth of bladder tumors and breast tumors.

9.
Transl Cancer Res ; 13(4): 2026-2042, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38737700

RESUMEN

Background and Objective: Lysyl oxidase-like protein 4 (LOXL4) is a secreted copper-dependent amine oxidase involved in the assembly and maintenance of extracellular matrix (ECM), playing a critical role in ECM formation and repair. Tumor-stroma interactions and ECM dysregulation are closely associated with the mechanisms underlying tumor initiation and progression. LOXL4 is the latest identified member of the lysyl oxidase (LOX) protein family. Currently, there is limited and controversial research on the role of LOXL4 in human malignancies. Its specific regulatory pathways, mechanisms, and roles in the occurrence, development, and treatment of malignancies remain incompletely understood. This article aims to illustrate the primary protein structure and the function of LOXL4 protein, and the relationship between LOXL4 protein and the occurrence and development of human malignant tumors to provide a reference for further clinical research. Methods: We searched the English literature on LOXL4 in the occurrence and development of various malignant tumors in PubMed and Web of Science. The search keywords include "cancer" "LOXL4" "malignant tumor" "tumorigenesis and development", etc. Key Content and Findings: LOXL4 is up-regulated in human gastric cancer, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, esophageal carcinoma and colorectal cancer, but down-regulated in human bladder cancer and lung cancer and inhibits tumor growth. There are two conflicting reports of both upregulation and downregulation in hepatocellular carcinoma, suggesting that LOXL4 has a bidirectional effect of promoting or inhibiting cancer in different types of human malignant tumors. We further explore the application prospect of LOXL4 protein in the study of malignant tumors, laying a theoretical foundation for the clinical diagnosis, treatment and screening of prognostic markers of malignant tumors. Conclusions: LOXL4 exerts a bidirectional regulatory role, either inhibiting or promoting tumors depending on the type of cancer. We still need more research to further confirm the molecular mechanism of LOXL4 in cancer progression.

10.
Cell Mol Immunol ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740922

RESUMEN

Eomesodermin (Eomes) is a critical factor in the development of natural killer (NK) cells, but its precise role in temporal and spatial coordination during this process remains unclear. Our study revealed that Eomes plays distinct roles during the early and late stages of NK cell development. Specifically, the early deletion of Eomes via the CD122-Cre transgene resulted in significant blockade at the progenitor stage due to the downregulation of KLF2, another important transcription factor. ChIP-seq revealed direct binding of Eomes to the conserved noncoding sequence (CNS) of Klf2. Utilizing the CHimeric IMmune Editing (CHIME) technique, we found that deletion of the CNS region of Klf2 via CRISPRi led to a reduction in the NK cell population and developmental arrest. Moreover, constitutive activation of this specific CNS region through CRISPRa significantly reversed the severe defects in NK cell development caused by Eomes deficiency. Conversely, Ncr1-Cre-mediated terminal deletion of Eomes expedited the transition of NK cell subsets from the CD27+CD11b+ phenotype to the CD27-CD11b+ phenotype. Late-stage deficiency of Eomes led to a significant increase in T-bet expression, which subsequently increased the expression of the transcription factor Zeb2. Genetic deletion of one allele of Tbx21, encoding T-bet, effectively reversed the aberrant differentiation of Eomes-deficient NK cells. In summary, we utilized two innovative genetic models to elucidate the intricate mechanisms underlying Eomes-mediated NK cell commitment and differentiation.

11.
Front Endocrinol (Lausanne) ; 15: 1366360, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38745950

RESUMEN

Introduction: This study aimed to explore the effect of cryopreservation duration after blastocyst vitrification on the singleton birth-weight of newborns to assess the safety of long-term preservation of frozen-thawed blastocyst transfer (FBT) cycles. Methods: This was a retrospective observational study conducted at the Gynecological Endocrinology and Assisted Reproduction Center of the Peking Union Medical College Hospital. Patients who gave birth to singletons between January 2006 and December 2021 after undergoing FBT cycles were included. Five groups were formed according to the duration of cryopreservation of embryos at FBT: Group I included 274 patients with a storage time < 3 months. Group II included 607 patients with a storage time of 3-6 months. Group III included 322 patients with a storage time of 6-12 months. Group IV included 190 patients with a storage time of 12-24 months. Group V included 118 patients with a storage time of > 24 months. Neonatal outcomes were compared among the groups. Multivariate linear regression analysis was performed to evaluate birth-weights and other birth-related outcomes. Results: A total of 1,511 patients were included in the analysis. The longest cryopreservation period was 12 years. The birth-weights of neonates in the five groups were 3344.1 ± 529.3, 3326.1 ± 565.7, 3260.3 ± 584.1, 3349.9 ± 582.7, and 3296.7 ± 491.9 g, respectively (P > 0.05). The incidences of preterm birth, very preterm birth, low birth-weight, and very low birth-weight were similar in all groups (P > 0.05). The large-for-gestational-age and small-for-gestational-age rates did not differ significantly among the groups (P > 0.05). After adjusting for confounding factors that may affect neonatal outcomes, a trend for an increased risk of low birth-weight with prolonged cryopreservation was observed. However, cryopreservation duration and neonatal birth-weight were not significantly correlated (P > 0.05). Conclusion: The duration of cryopreservation after blastocyst vitrification with an open device for more than 2 years had no significant effect on the birth-weight of FBT singletons; however, attention should be paid to a possible increase in the risk of low birth-weight.


Asunto(s)
Peso al Nacer , Criopreservación , Transferencia de Embrión , Vitrificación , Humanos , Criopreservación/métodos , Femenino , Estudios Retrospectivos , Transferencia de Embrión/métodos , Adulto , Embarazo , Peso al Nacer/fisiología , Recién Nacido , Blastocisto , Factores de Tiempo , Fertilización In Vitro/métodos , Masculino , Resultado del Embarazo/epidemiología
12.
JBI Evid Synth ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38745480

RESUMEN

OBJECTIVE: This scoping review will identify the patterns of survival, treatment, and recurrence among Hispanic and/or Latino/a/x (H/L) patients with colorectal cancer (CRC) living in the United States (US) and Puerto Rico. Additionally, population- and individual-level determinants of cancer outcomes among H/L CRC patients will be mapped to highlight under-reported/under-investigated research areas. INTRODUCTION: CRC is the third most common cancer excluding skin cancers in the US. Unlike non-Hispanic White populations, cancer is the number one cause of death in H/L populations and currently represents 21% of total deaths. Despite this, a lack of consensus exists on CRC outcomes for H/L patients. Most research on H/L individuals has examined incidence and screening of CRC, with fewer studies focusing on cancer outcomes. INCLUSION CRITERIA: All epidemiological study designs and systematic reviews will be considered. The review will only include peer-reviewed studies that report on survival, treatment, and/or recurrence patterns for H/L patients with CRC residing in the US and Puerto Rico. METHODS: A 3-step search with a 2-stage study selection process will be followed, as recommended by JBI and Arksey and O'Malley. Databases to be searched will include MEDLINE (PubMed), Embase (Ovid), and Scopus. A data extraction tool will be designed based on JBI recommendations. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRSIMA-ScR) will be used, with the results presented in a PRISMA diagram. Publications in English from database inception to the present will be considered.The protocol has been registered in Open Science Framework: https://osf.io/y6qf5.

13.
Front Nutr ; 11: 1296774, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38757129

RESUMEN

Background: Green tea intake has been reported to improve the clinical outcomes of patients with cardiovascular diseases or cancer. It may have a certain role in the development of venous thromboembolism (VTE) among cancer patients. The current study aimed to address this issue, which has been understudied. Methods: We carried out a retrospective study to explore the role of green tea intake in cancer patients. Patients with and without green tea intake were enrolled in a 1:1 ratio by using propensity scoring matching. The primary and secondary outcomes were VTE development and mortality 1 year after cancer diagnosis, respectively. Results: The cancer patients with green tea intake (n = 425) had less VTE development (10 [2.4%] vs. 23 [5.4%], p = 0.021), VTE-related death (7 [1.6%] vs. 18 [4.2%], p = 0.026), and fatal pulmonary embolism (PE) (3 [0.7%] vs. 12 [2.8%], p = 0.019), compared with those without green tea intake (n = 425). No intake of green tea was correlated with an increase in VTE development (multivariate hazard ratio (HR) 1.758 [1.476-2.040], p < 0.001) and VTE-related mortality (HR 1.618 [1.242-1.994], p = 0.001), compared with green tea intake. Patients with green tea intake less than 525 mL per day had increased VTE development (area under the curve (AUC) 0.888 [0.829-0.947], p < 0.001; HR1.737 [1.286-2.188], p = 0.001) and VTE-related mortality (AUC 0.887 [0.819-0.954], p < 0.001; HR 1.561 [1.232-1.890], p = 0.016) than those with green tea intake more than 525 mL per day. Green tea intake caused a decrease in platelet (p < 0.001) instead of D-dimer (p = 0.297). The all-cause mortality rates were similar between green tea (39 [9.2%]) and non-green tea (48 [11.3%]) intake groups (p = 0.308), whereas the VTE-related mortality rate in the green tea intake group (7 [1.6%]) was lower than that of the non-green tea intake group (18 [4.2%]) (p = 0.026). The incidences of adverse events were similar between the green tea and non-green tea intake groups. Conclusion: In conclusion, the current study suggests that green tea intake reduces VTE development and VTE-related mortality in cancer patients, most likely through antiplatelet mechanisms. Drinking green tea provides the efficacy of thromboprophylaxis for cancer patients.

14.
Med Oncol ; 41(6): 159, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38761335

RESUMEN

RNA modification has garnered increasing attention in recent years due to its pivotal role in tumorigenesis and immune surveillance. N6-methyladenosine (m6A) modification is the most prevalent RNA modification, which can affect the expression of RNA by methylating adenylate at the sixth N position to regulate the occurrence and development of tumors. Dysregulation of m6A affects the activation of cancer-promoting pathways, destroys immune cell function, maintains immunosuppressive microenvironment, and promotes tumor cell growth. In this review, we delve into the latest insights into how abnormalities in m6A modification in both tumor and immune cells orchestrate immune evasion through the activation of signaling pathways. Furthermore, we explore how dysregulated m6A modification in tumor cells influences immune cells, thereby regulating tumor immune evasion via interactions within the tumor microenvironment (TME). Lastly, we highlight recent discoveries regarding specific inhibitors of m6A modulators and the encapsulation of m6A-targeting nanomaterials for cancer therapy, discussing their potential applications in immunotherapy.


Asunto(s)
Adenosina , Inmunoterapia , Neoplasias , Microambiente Tumoral , Humanos , Inmunoterapia/métodos , Microambiente Tumoral/inmunología , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/inmunología , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/patología , Escape del Tumor/inmunología , Animales , Evasión Inmune/inmunología , Transducción de Señal/inmunología
15.
Mol Cancer ; 23(1): 108, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38762484

RESUMEN

Immune evasion contributes to cancer growth and progression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) and programmed cell death ligands (PD-Ls) are considered to be the major immune checkpoint molecules. The interaction of PD-1 and PD-L1 negatively regulates adaptive immune response mainly by inhibiting the activity of effector T cells while enhancing the function of immunosuppressive regulatory T cells (Tregs), largely contributing to the maintenance of immune homeostasis that prevents dysregulated immunity and harmful immune responses. However, cancer cells exploit the PD-1/PD-L1 axis to cause immune escape in cancer development and progression. Blockade of PD-1/PD-L1 by neutralizing antibodies restores T cells activity and enhances anti-tumor immunity, achieving remarkable success in cancer therapy. Therefore, the regulatory mechanisms of PD-1/PD-L1 in cancers have attracted an increasing attention. This article aims to provide a comprehensive review of the roles of the PD-1/PD-L1 signaling in human autoimmune diseases and cancers. We summarize all aspects of regulatory mechanisms underlying the expression and activity of PD-1 and PD-L1 in cancers, including genetic, epigenetic, post-transcriptional and post-translational regulatory mechanisms. In addition, we further summarize the progress in clinical research on the antitumor effects of targeting PD-1/PD-L1 antibodies alone and in combination with other therapeutic approaches, providing new strategies for finding new tumor markers and developing combined therapeutic approaches.


Asunto(s)
Antígeno B7-H1 , Neoplasias , Receptor de Muerte Celular Programada 1 , Humanos , Neoplasias/metabolismo , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/etiología , Neoplasias/genética , Receptor de Muerte Celular Programada 1/metabolismo , Antígeno B7-H1/metabolismo , Animales , Transducción de Señal , Regulación Neoplásica de la Expresión Génica
17.
CJC Pediatr Congenit Heart Dis ; 3(2): 57-66, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38774679

RESUMEN

Background: A national registry of congenital heart disease (CHD) would facilitate project initiation, decrease costs, increase statistical power, and avoid duplication. Establishing such registries poses numerous challenges, but the current Canadian research ecosystem in CHD is well positioned to meet them. We assessed the feasibility of building a province-wide CHD registry by automatically identifying people with CHD and extracting their native cardiac anatomy from multiple clinical data sources, without the need for manual data entry. Methods: We designed a CHD registry of all fetuses and children with at least 1 echocardiographic report confirming CHD since 2000. We interfaced the registry with several clinical and echocardiography data sources from all paediatric cardiology programmes in Québec. Results: We extracted 885,287 echocardiogram reports and 70,121 clinical records. We identified CHD in 43,452 children and 4682 fetuses. There were 1128 (2.3%) cases with files in multiple institutions, and patients with more complex CHD were 3 times more likely to be seen in more than 1 institution. So far, the registry has been used to build and link CHD cohorts for 7 distinct projects. Conclusions: We demonstrated the feasibility of a baseline CHD registry in Québec without the need for manual data entry, in which other CHD research projects could be nested. This could serve as a blueprint to expand the registry and to develop an integrated approach where data gathered in caring for patients with CHD serve as data layers that incrementally contribute to a national cohort, for which data remain easily accessible and usable.


Contexte: Un registre national des cardiopathies congénitales (CC) pourrait faciliter le lancement de projets de recherche, en diminuer les coûts, en améliorer la puissance statistique tout en évitant les redondances. La mise en place de tels registres pose de nombreux défis, mais l'écosystème de recherche canadien dans le domaine de la CC est bien placé pour y répondre. Nous avons évalué la faisabilité de la mise en place d'un registre des CC à l'échelle provinciale par l'identification automatique des personnes atteintes de CC et l'extraction de leur anatomie cardiaque native à partir de plusieurs sources de données cliniques, sans nécessiter de saisie manuelle de données. Méthodologie: Nous avons conçu un registre des CC incluant tous les fœtus et les enfants pour qui au moins un rapport d'évaluation électrocardiographique confirmait la présence d'une CC depuis 2000. Le registre a été mis en relation avec plusieurs sources de données cliniques et échocardiographiques provenant de tous les programmes en cardiologie pédiatrique au Québec. Résultats: Nous avons extrait 885 287 rapports d'échocardiographie et 70 121 dossiers cliniques. La présence d'une CC a été établie chez 43 452 enfants et 4 682 fœtus. Dans 1 128 cas (2,3 %), un dossier existait dans plus d'un établissement. Les patients présentant des CC plus complexes étaient 3 fois plus susceptibles d'être suivis dans plus d'un établissement. Jusqu'à présent, le registre a été utilisé pour établir et mettre en relation des cohortes de patients atteints de CC pour sept projets de recherche distincts. Conclusions: Nous avons démontré la faisabilité de la mise en place d'un registre de référence des CC au Québec sans recours à la saisie manuelle de données, dans lequel peuvent se nicher d'autres projets de recherche sur les CC. Notre démarche pourrait servir de prototype pour une expansion du registre et pour une approche d'intégration des données recueillies dans la prestation de soins aux patients atteints de CC, afin de former des couches de données qui s'ajoutent au fur et à mesure à une cohorte nationale, avec des données faciles à obtenir et à utiliser.

18.
J Acoust Soc Am ; 155(5): 3436-3446, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38780196

RESUMEN

Fueled by the concepts of topological insulators, analogous topological acoustics offer an alternative approach to manipulate sound. Theoretical proposals for subwavelength acoustic topological insulators are considered to be ideal effective parameters or utilizeing artificial coiling-space metamaterials. However, the corresponding realization using realistic soft metamaterials remains challenging. In this study, we present the design of an acoustic subwavelength second-order topological insulator using nanoscale porous solid material, silica aerogel, which supports pseudospin-dependent topological edge and corner states simultaneously. Through simulations and experiments, we demonstrate that silica aerogel can function as a soft acoustic metamaterial at the subwavelength scale. By embedding silica aerogel in an air matrix to construct a honeycomb lattice, a double Dirac cone is obtained. A topological phase transition is induced by expanding or contracting the supercell, resulting in band inversion. Additionally, we propose topologically robust acoustic transmission along the one-dimensional edge. Furthermore, we discover that the proposed sonic crystal sustains zero-dimensional corner states, which can efficiently confine energy at subwavelength corners. These findings offer potential for the realization of subwavelength topological acoustic devices using realistic soft metamaterials.

19.
Heliyon ; 10(10): e30941, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38779031

RESUMEN

Prostate adenocarcinoma (PRAD), driven by both genetic and epigenetic factors, is a common malignancy that affects men worldwide. We aimed to identify and characterize differentially expressed epigenetic-related genes (ERGs) in PRAD and investigate their potential roles in disease progression and prognosis. We used PRAD samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to identify prognosis-associated ERGs. Thirteen ERGs with two distinct expression profiles were identified through consensus clustering. Gene set variation analysis highlighted differences in pathway activities, particularly in the Hedgehog and Notch pathways. Higher epigenetic scores correlated with favorable prognosis and improved immunotherapeutic response. Experimental validation underscored the importance of CBX3 and KAT2A, suggesting their pivotal roles in PRAD. This study provides crucial insights into the epigenetic scoring approach and presents a promising prognostic tool, with CBX3 and KAT2A as key players. These findings pave the way for targeted and personalized interventions for the treatment of PRAD.

20.
Adv Mater ; : e2401533, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38794830

RESUMEN

The precise construction of hierarchically long-range ordered structures using molecules as fundamental building blocks can fully harness their anisotropy and potential. However, the three-dimensional (3D), high-precision, and single-step directional assembly of molecules is a long-pending challenge. Here, we propose a 3D directional molecular assembly strategy via femtosecond laser direct writing (FsLDW) and demonstrate the feasibility of this approach using liquid crystal (LC) molecules as an illustrative example. The physical mechanism for femtosecond (fs) laser-induced assembly of LC molecules has been investigated, and precise 3D arbitrary assembly of LC molecules has been achieved by defining the discretized laser scanning pathway. Additionally, an LC-based Fresnel zone plate array with polarization selection and colorization imaging functions has been fabricated to further illustrate the potential of this method. This study not only introduces a 3D high-resolution alignment method for LC-based functional devices but also establishes a universal protocol for the precise 3D directional assembly of anisotropic molecules. This article is protected by copyright. All rights reserved.

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