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1.
Ecotoxicol Environ Saf ; 282: 116715, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39002378

RESUMEN

Intercropping with hyperaccumulators can facilitate the safe utilization of cadmium-contaminated soil. However, the effectiveness of this approach is influenced by plant species and varieties, which necessitates research on optimal plant consortia. In this study, 8 tomato varieties (3 cherry tomatoes and 5 common large-fruit tomatoes) were intercropped with Sedum alfredii in a moderately Cd-contaminated vegetable field. The results showed that the Cd concentration in the fruits of common large-fruit tomato varieties under monoculture was 1.03-1.50 mg/kg, while that in the fruits of cherry tomato varieties was 0.67-0.71 mg/kg. After intercropping with S. alfredii, the fruit Cd concentrations of Hangza 501, Hangza 503, and Hangza 108 decreased by 16.42 %, 19.72 %, and 6.76 %, respectively, while those of the other varieties significantly increased, except for those of Hangza 8. In contrast, the shoot Cd concentration of cherry tomatoes was greater than that of large-fruit tomatoes under monoculture. Furthermore, a significant increase in the shoot Cd concentration was noted in the Hangza 501, Hangza 503 and Hangza 603 plants following intercropping. Additionally, intercropping with S. alfredii increased the concentration of soluble sugars in the fruits of Hangza 8, Hangza 501, Hangza 503 and Hangza 603 by 4.66 %, 17.91 %, 10.60 % and 17.88 %, respectively. Intercropping with tomatoes resulted in a decrease in both the biomass and Cd uptake of S. alfredii. Interestingly, the inhibitory effect on S. alfredii was less pronounced when intercropped with cherry tomatoes than when intercropped with large-fruit tomatoes. Among the intercropping treatments, S. alfredii exhibited the greatest total Cd accumulation (0.06 mg/plant) when intercropped with Hangza 503. In conclusion, the cherry tomato variety Hangza 503 was the most suitable for intercropping with S. alfredii and can be used safely for vegetable production and simultaneous phytoremediation of polluted soil. Our findings suggest that strategic selection of tomato varieties can optimize the effectiveness of "phytoextraction coupled with agro-safe production" technology for managing soil Cd concentrations.

2.
Cancer Immunol Res ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39051632

RESUMEN

Immune composition within the tumor microenvironment (TME) plays a central role in the propensity of cancer to metastasize and to respond to therapy. Previous studies suggested that the metastatic TME is immune suppressed. However, limited accessibility to multiple metastatic sites within patients has made assessment of the immune TME in the context of multi-organ metastases difficult. We utilized a rapid postmortem tissue collection protocol to assess immune composition in numerous sites of breast cancer metastasis and paired tumor-free tissues. Metastases were found to have comparable immune cell densities and composition to paired tumor-free tissues of the same organ type. In contrast, immune cell densities in both metastatic and tumor-free tissues were significantly different between organ types, with lung immune infiltration consistently greater than liver. These immune profiling results were consistent between both flow cytometry and multiplex immunofluorescence-based spatial analysis. Furthermore, we found granulocytes were a predominant tumor-infiltrating immune cell in both lung and liver metastases and these granulocytes made up the majority of PD-L1-expressing cells in many tissue sites. We also identified distinct potential mechanisms of immunosuppression in lung and liver metastases, with lung having increased expression of PD-L1+ antigen-presenting cells and liver having higher numbers of activated regulatory T cells and HLA-DRlow monocytes. Together these results demonstrate that immune contexture of metastases is dictated by organ type, and that immunotherapy strategies may benefit from unique tailoring to tissue-specific features of the immune TME.

3.
Biomed Mater ; 19(4)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38756029

RESUMEN

Hard tissue engineering scaffolds especially 3D printed scaffolds were considered an excellent strategy for craniomaxillofacial hard tissue regeneration, involving crania and facial bones and teeth. Porcine treated dentin matrix (pTDM) as xenogeneic extracellular matrix has the potential to promote the stem cell differentiation and mineralization as it contains plenty of bioactive factors similar with human-derived dentin tissue. However, its application might be impeded by the foreign body response induced by the damage-associated molecular patterns of pTDM, which would cause strong inflammation and hinder the regeneration. Ceria nanoparticles (CNPs) show a great promise at protecting tissue from oxidative stress and influence the macrophages polarization. Using 3D-bioprinting technology, we fabricated a xenogeneic hard tissue scaffold based on pTDM xenogeneic TDM-polycaprolactone (xTDM/PCL) and we modified the scaffolds by CNPs (xTDM/PCL/CNPs). Through series ofin vitroverification, we found xTDM/PCL/CNPs scaffolds held promise at up-regulating the expression of osteogenesis and odontogenesis related genes including collagen type 1, Runt-related transcription factor 2 (RUNX2), bone morphogenetic protein-2, osteoprotegerin, alkaline phosphatase (ALP) and DMP1 and inducing macrophages to polarize to M2 phenotype. Regeneration of bone tissues was further evaluated in rats by conducting the models of mandibular and skull bone defects. Thein vivoevaluation showed that xTDM/PCL/CNPs scaffolds could promote the bone tissue regeneration by up-regulating the expression of osteogenic genes involving ALP, RUNX2 and bone sialoprotein 2 and macrophage polarization into M2. Regeneration of teeth evaluated on beagles demonstrated that xTDM/PCL/CNPs scaffolds expedited the calcification inside the scaffolds and helped form periodontal ligament-like tissues surrounding the scaffolds.


Asunto(s)
Cerio , Matriz Extracelular , Nanopartículas , Osteogénesis , Impresión Tridimensional , Ingeniería de Tejidos , Andamios del Tejido , Animales , Andamios del Tejido/química , Ingeniería de Tejidos/métodos , Porcinos , Matriz Extracelular/metabolismo , Cerio/química , Nanopartículas/química , Ratas , Poliésteres/química , Dentina/química , Humanos , Regeneración Ósea/efectos de los fármacos , Odontogénesis , Diferenciación Celular , Regeneración , Macrófagos/metabolismo , Cráneo , Ratas Sprague-Dawley
4.
Artículo en Inglés | MEDLINE | ID: mdl-38727409

RESUMEN

BACKGROUND: Vascular tumorous thrombosis is a crucial pathological feature of malignant tumors that is closely associated with lymph node metastasis and is considered a form of tumor micrometastasis. Two downregulated genes, catenin alpha 3 (CTNNA3) and FERM and PDZ domain-containing 4 (FRMPD4), were selected by analyzing the differential expression of vascular tumorous thrombus in colon adenocarcinoma and paracancerous tissues. Further investigation revealed their potential role in the development of vascular tumorous thrombosis in colon adenocarcinomas. MATERIALS AND METHODS: Candidate genes for vascular tumorous thrombosis in colon adenocarcinoma were screened using GSE127069, and pan-cancer verification and immune infiltration analysis were performed. The relationship between gene expression and vascular tumorous thrombosis was analyzed based on the level of gene mutations using cBioPortal. Finally, the collected clinical samples were used to verify expression. RESULTS: CTNNA3 and FRMPD4 were expressed at low levels in the vascular tumorous thrombosis of colon adenocarcinoma and positively correlated with microsatellite instability. They are also closely related to the immune microenvironment and the infiltration of immune cell subtypes. Based on gene mutation analysis, gene deletion is suggested to be related to vascular invasion indicators. Finally, protein and messenger ribonucleic acid (mRNA) expression of CTNNA3 and FRMPD4 were downregulated in the vascular tumorous thrombosis samples of colon adenocarcinoma compared to normal glands from paracancerous tissues. CONCLUSION: Our study suggests that CTNNA3 and FRMPD4 could be promising biomarkers for vascular tumorous thrombosis in colon adenocarcinoma, potentially enabling the identification of micrometastases in this type of cancer. These findings suggest a novel strategy for the detection and management of colon adenocarcinomas.

5.
ACS Nano ; 18(22): 14020-14028, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38764286

RESUMEN

The electrochemical CO2 reduction reaction (CO2RR) has emerged as a promising approach for sustainable carbon cycling and valuable chemical production. Various methods and strategies have been explored to boost CO2RR performance. One of the most promising strategies includes the construction of stable ionic interfaces on metallic or molecular catalysts using organic or inorganic cations, which has demonstrated a significant improvement in catalytic performance. The stable ionic interface is instrumental in adjusting adsorption behavior, influencing reactive intermediates, facilitating mass transportation, and suppressing the hydrogen evolution reaction, particularly under acidic conditions. In this Perspective, we provide an overview of the recent advancements in building ionic interfaces in the electrocatalytic process and discuss the application of this strategy to improve the CO2RR performance of metallic and molecular catalysts. We aim to convey the future trends and opportunities in creating ionic interfaces to further enhance carbon utilization efficiency and the productivity of CO2RR products. The emphasis of this Perspective lies in the pivotal role of ionic interfaces in catalysis, providing a valuable reference for future research in this critical field.

6.
Adv Mater ; 36(32): e2402979, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38811011

RESUMEN

Copper (Cu) nanomaterials are a unique kind of electrocatalysts for high-value multi-carbon production in carbon dioxide reduction reaction (CO2RR), which holds enormous potential in attaining carbon neutrality. However, phase engineering of Cu nanomaterials remains challenging, especially for the construction of unconventional phase Cu-based asymmetric heteronanostructures. Here the site-selective growth of Cu on unusual phase gold (Au) nanorods, obtaining three kinds of heterophase fcc-2H-fcc Au-Cu heteronanostructures is reported. Significantly, the resultant fcc-2H-fcc Au-Cu Janus nanostructures (JNSs) break the symmetric growth mode of Cu on Au. In electrocatalytic CO2RR, the fcc-2H-fcc Au-Cu JNSs exhibit excellent performance in both H-type and flow cells, with Faradaic efficiencies of 55.5% and 84.3% for ethylene and multi-carbon products, respectively. In situ characterizations and theoretical calculations reveal the co-exposure of 2H-Au and 2H-Cu domains in Au-Cu JNSs diversifies the CO* adsorption configurations and promotes the CO* spillover and subsequent C-C coupling toward ethylene generation with reduced energy barriers.

7.
Small Methods ; : e2400118, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38597770

RESUMEN

The rising global population and improved living standards have led to an alarming increase in non-communicable diseases, notably cardiovascular and chronic respiratory diseases, posing a severe threat to human health. Wearable sensing devices, utilizing micro-sensing technology for real-time monitoring, have emerged as promising tools for disease prevention. Among various sensing platforms, graphene-based sensors have shown exceptional performance in the field of micro-sensing. Laser-induced graphene (LIG) technology, a cost-effective and facile method for graphene preparation, has gained particular attention. By converting polymer films directly into patterned graphene materials at ambient temperature and pressure, LIG offers a convenient and environmentally friendly alternative to traditional methods, opening up innovative possibilities for electronic device fabrication. Integrating LIG-based sensors into health monitoring systems holds the potential to revolutionize health management. To commemorate the tenth anniversary of the discovery of LIG, this work provides a comprehensive overview of LIG's evolution and the progress of LIG-based sensors. Delving into the diverse sensing mechanisms of LIG-based sensors, recent research advances in the domain of health monitoring are explored. Furthermore, the opportunities and challenges associated with LIG-based sensors in health monitoring are briefly discussed.

8.
Opt Express ; 32(6): 9562-9572, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38571187

RESUMEN

We demonstrated a high-performance partially corrugated waveguide distributed feedback (PCW-DFB) laser with high output power, low relative intensity noise (RIN) and narrow linewidth. By introducing offset quantum-well structure that provides enough threshold gain difference for single transverse mode operation, the laser can achieve single mode behavior with an 8-µm-wide ridge waveguide. The laser has been designed by the simulation model based on the coupled wave equations, and the fabricated PCW-DFB laser with the cavity length of 1.3 mm exhibited an output power higher than 190 mW. Stable single mode characteristics have been achieved with a side-mode suppression-ratio (SMSR) over 55 dB. The RIN was less than -160.5 dB/Hz at an injection current of 470 mA, and the linewidth reached 45 kHz.

9.
Int Dent J ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38631944

RESUMEN

OBJECTIVES: Investigate the geographical distribution of private dental practices in major Chinese cities and analyze the variables influencing this distribution. METHODS: This study used Python to extract various types of Point of Interest (POI) data spanning from 2016 to 2022 from the AutoNavi map. A 1km*1km grid was constructed to establish the study sample. Additional spatial pattern data, including nighttime lighting, population, and air quality data, were integrated into this grid. Global Moran's I index was used to analyze the spatial autocorrelation. The spatial lag model was used to explore the influencing factors of private dental practice distribution. RESULTS: This study reveals a specific clustering pattern for private dental practices in major Chinese cities. The primary influencing factors include nighttime lights, population density, and housing prices, suggesting that dental practices are typically concentrated in highly developed regions with dense populations and high housing costs. Additionally, we discovered that patterns vary across different metropolises, with the most pronounced clustering patterns and substantial inequalities found in the most developed areas. CONCLUSIONS: This study establishes that factors such as regional development and population density positively correlate with private dental practice. Additionally, it reveals a strong mutual correlation in the clustering of dental practices, which does not show a substantial correlation with public resources. Finally, it suggests that the spatial heterogeneity pattern implies a rising necessity to tackle inequality issues within urban areas as economic development progresses.

10.
Biomed Mater ; 19(4)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38653259

RESUMEN

The decellularized matrix has a great potential for tissue remodeling and regeneration; however, decellularization could induce host immune rejection due to incomplete cell removal or detergent residues, thereby posing significant challenges for its clinical application. Therefore, the selection of an appropriate detergent concentration, further optimization of tissue decellularization technique, increased of biosafety in decellularized tissues, and reduction of tissue damage during the decellularization procedures are pivotal issues that need to be investigated. In this study, we tested several conditions and determined that 0.1% Sodium dodecyl sulfate and three decellularization cycles were the optimal conditions for decellularization of pulp tissue. Decellularization efficiency was calculated and the preparation protocol for dental pulp decellularization matrix (DPDM) was further optimized. To characterize the optimized DPDM, the microstructure, odontogenesis-related protein and fiber content were evaluated. Our results showed that the properties of optimized DPDM were superior to those of the non-optimized matrix. We also performed the 4D-Label-free quantitative proteomic analysis of DPDM and demonstrated the preservation of proteins from the natural pulp. This study provides a optimized protocol for the potential application of DPDM in pulp regeneration.


Asunto(s)
Matriz Extracelular Descelularizada , Pulpa Dental , Proteómica , Ingeniería de Tejidos , Andamios del Tejido , Pulpa Dental/citología , Proteómica/métodos , Animales , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Matriz Extracelular Descelularizada/química , Dodecil Sulfato de Sodio/química , Humanos , Odontogénesis , Matriz Extracelular/metabolismo , Matriz Extracelular/química
11.
Front Bioeng Biotechnol ; 12: 1356580, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38456006

RESUMEN

Tooth loss or damage poses great threaten to oral and general health. While contemporary clinical treatments have enabled tooth restoration to a certain extent, achieving functional tooth regeneration remains a challenging task due to the intricate and hierarchically organized architecture of teeth. The past few decades have seen a rapid development of three-dimensional (3D) printing technology, which has provided new breakthroughs in the field of tissue engineering and regenerative dentistry. This review outlined the bioactive materials and stem/progenitor cells used in dental regeneration, summarized recent advancements in the application of 3D printing technology for tooth and tooth-supporting tissue regeneration, including dental pulp, dentin, periodontal ligament, alveolar bone and so on. It also discussed current obstacles and potential future directions, aiming to inspire innovative ideas and encourage further development in regenerative medicine.

12.
NPJ Precis Oncol ; 8(1): 81, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38553598

RESUMEN

The biology of metastatic breast cancer (MBC) is understudied, primarily due to the difficulty of procuring multiple samples from patients with oligometastatic breast cancer. We developed a rapid postmortem tissue procurement program that allows the collection and analysis of numerous metastatic lesions, subclinical locations, and potential pre-metastatic niches that fall within this scope. We conducted a rapid postmortem tissue collection study on 9 patients with MBC. Patients and their families consented to donate tissues immediately after death in an IRB-approved study. Various disease subtypes, progression histories, organ involvement, and final causes of death are reported. In patients with hormone receptor-positive (HR+) disease, estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 expression were heterogeneous across metastatic lesions within individual patients. Disease phenotype at the end of life trended toward complete loss of HR expression. Nearly all (n = 7) patients exhibited extensive tumor involvement of additional organs that had not been previously diagnosed clinically and were not retrospectively visible on recent imaging. Of these seven individuals, three included organs uncommonly associated with MBC: kidney, spleen, pancreas, and ovary. Finally, we identified clinically undetectable micrometastases in several organs uncommonly involved in MBC. Our findings raise several clinically relevant questions regarding the mechanisms of metastatic progression. Insights from this study argue for better surveillance strategies for monitoring MBC. We highlight the need to capture more accurate biomarker information in the context of heterogeneous disease and urge the consideration of treatment strategies that combine multiple targeted therapies.

13.
Stem Cell Reports ; 19(3): 399-413, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38428414

RESUMEN

Degenerative bone disorders have a significant impact on global health, and regeneration of articular cartilage remains a challenge. Existing cell therapies using mesenchymal stromal cells (MSCs) have shown limited efficacy, highlighting the necessity for alternative stem cell sources. Here, we have identified and characterized MSX1+ mesenchymal progenitor cells in the developing limb bud with remarkable osteochondral-regenerative and microenvironment-adaptive capabilities. Single-cell sequencing further revealed the presence of two major cell compositions within the MSX1+ cells, where a distinct PDGFRAlow subset retained the strongest osteochondral competency and could efficiently regenerate articular cartilage in vivo. Furthermore, a strategy was developed to generate MSX1+PDGFRAlow limb mesenchyme-like (LML) cells from human pluripotent stem cells that closely resembled their mouse counterparts, which were bipotential in vitro and could directly regenerate damaged cartilage in a mouse injury model. Together, our results indicated that MSX1+PDGFRAlow LML cells might be a prominent stem cell source for human cartilage regeneration.


Asunto(s)
Cartílago Articular , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Ratones , Animales , Células Madre , Tratamiento Basado en Trasplante de Células y Tejidos , Mesodermo , Trasplante de Células Madre Mesenquimatosas/métodos , Diferenciación Celular , Factor de Transcripción MSX1/genética
14.
Glob Chang Biol ; 30(2): e17182, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38348761

RESUMEN

Biodiversity is considered important to the mitigation of global change impacts on ecosystem multifunctionality in terrestrial ecosystems. However, potential mechanisms through which biodiversity maintains ecosystem multifunctionality under global change remain unclear. We grew 132 plant communities with two levels of plant diversity, crossed with treatments based on 10 global change factors (nitrogen deposition, soil salinity, drought, plant invasion, simulated grazing, oil pollution, plastics pollution, antibiotics pollution, heavy metal pollution, and pesticide pollution). All global change factors negatively impacted ecosystem multifunctionality, but negative impacts were stronger in high compared with low diversity plant communities. We explored potential mechanisms for this unexpected result, finding that the inhibition of selection effects (i.e., selection for plant species associated with high ecosystem functioning) contributed to sensitivity of ecosystem multifunctionality to global change. Specifically, global change factors decreased the abundance of novel functional plants (i.e., legumes) in high but not low diversity plant communities. The negative impacts of global change on ecosystem multifunctionality were also mediated by increased relative abundance of fungal plant pathogens (identified from metabarcoding of soil samples) and their negative relationship with the abundance of novel functional plants. Taken together, our experiment highlights the importance of protecting high diversity plant communities and legumes, and managing fungal pathogens, to the maintenance of ecosystem multifunctionality in the face of complex global change.


Asunto(s)
Ecosistema , Fabaceae , Biodiversidad , Plantas , Suelo , Contaminación Ambiental
15.
Res Sq ; 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38343849

RESUMEN

The prevalence of knee osteoarthritis (OA) is widespread and the heterogeneous patient factors and clinical symptoms in OA patients impede developing personalized treatments for OA patients. In this study, we used unsupervised and supervised machine learning to organize the heterogeneity in knee OA patients and predict disease progression in individuals from the Osteoarthritis Initiative (OAI) dataset. We identified four distinct knee OA phenotypes using unsupervised learning that were defined by nutrition, disability, stiffness, and pain (knee and back) and were strongly related to disease fate. Interestingly, the absence of supplemental vitamins from an individual's diet was protective from disease progression. Moreover, we established a phenotyping tool and prognostic model from 5 variables (WOMAC disability score of the right knee, WOMAC total score of the right knee, WOMAC total score of the left knee, supplemental vitamins and minerals frequency, and antioxidant combination multivitamins frequency) that can be utilized in clinical practice to determine the risk of knee OA progression in individual patients. We also developed a prognostic model to estimate the risk for total knee replacement and provide suggestions for modifiable variables to improve long-term knee health. This combination of unsupervised and supervised data-driven tools provides a framework to identify knee OA phenotype in a clinical scenario and personalize treatment strategies.

16.
Angew Chem Int Ed Engl ; 63(15): e202400414, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38348904

RESUMEN

Bipolar membranes (BPMs) have emerged as a promising solution for mitigating CO2 losses, salt precipitation and high maintenance costs associated with the commonly used anion-exchange membrane electrode assembly for CO2 reduction reaction (CO2RR). However, the industrial implementation of BPM-based zero-gap electrolyzer is hampered by the poor CO2RR performance, largely attributed to the local acidic environment. Here, we report a backbone engineering strategy to improve the CO2RR performance of molecular catalysts in BPM-based zero-gap electrolyzers by covalently grafting cobalt tetraaminophthalocyanine onto a positively charged polyfluorene backbone (PF-CoTAPc). PF-CoTAPc shows a high acid tolerance in BPM electrode assembly (BPMEA), achieving a high FE of 82.6 % for CO at 100 mA/cm2 and a high CO2 utilization efficiency of 87.8 %. Notably, the CO2RR selectivity, carbon utilization efficiency and long-term stability of PF-CoTAPc in BPMEA outperform reported BPM systems. We attribute the enhancement to the stable cationic shield in the double layer and suppression of proton migration, ultimately inhibiting the undesired hydrogen evolution and improving the CO2RR selectivity. Techno-economic analysis shows the least energy consumption (957 kJ/mol) for the PF-CoTAPc catalyst in BPMEA. Our findings provide a viable strategy for designing efficient CO2RR catalysts in acidic environments.

17.
EBioMedicine ; 101: 105035, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38401418

RESUMEN

BACKGROUND: While mutation-derived neoantigens are well recognized in generating anti-tumour T cell response, increasing evidences highlight the complex association between tumour mutation burden (TMB) and tumour infiltrating lymphocytes (TILs). The exploration of non-TMB determinants of active immune response could improve the prognosis prediction and provide guidance for current immunotherapy. METHODS: The transcriptomic and whole exome sequence data in The Cancer Genome Atlas were used to examine the relationship between TMB and exhausted CD8+ T cells (Tex), as an indicator of tumour antigen-specific T cells across nine major cancer types. Computational clustering analysis was performed on 4510 tumours to identify different immune profiles. NanoString gene expression analysis and single cell RNA-seq analysis using fresh human breast cancer were performed for finding validation. FINDINGS: TMB was found to be poorly correlated with active immune response in various cancer types. Patient clustering analysis revealed a group of tumours with abundant Tex but low TMB. In those tumours, we observed significantly higher expression of the stimulator of interferon genes (STING) signalling. Dendritic cells, particularly those of BATF3+ lineage, were also found to be essential for accumulation of Tex within tumours. Mechanistically, loss of genomic and cellular integrity, marked by decreased DNA damage repair, defective replication stress response, and increased apoptosis were shown to drive STING activation. INTERPRETATION: These results highlight that TMB alone does not fully predict tumour immune profiles, with STING signalling compensating for low TMB in non-hypermutated tumours to enhance anti-tumour immunity. Translating these results, STING agonists may benefit patients with non-hypermutated tumours. STING activation may serve as an additional biomarker to predict response to immune checkpoint blockades alongside TMB. Our research also unravelled the interplay between genomic instability and STING activation, informing potential combined chemotherapy targeting the axis of genomic integrity and immunotherapy. FUNDING: City of Hope Christopher Family Endowed Innovation Fund for Alzheimer's Disease and Breast Cancer Research in honor of Vineta Christopher; Breast Cancer Alliance Early Career Investigator Award; National Cancer Institute of the National Institutes of Health under award number R01CA256989 and R01CA240392.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Mutación , Pronóstico , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Biomarcadores de Tumor/genética , Antígenos de Neoplasias/genética
18.
Cell Rep Med ; 5(2): 101420, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38382468

RESUMEN

Tumor-associated macrophages (TAMs) are the predominant cells that express programmed cell death ligand 1 (PD-L1) within human tumors in addition to cancer cells, and PD-L1+ TAMs are generally thought to be immunosuppressive within the tumor immune microenvironment (TIME). Using single-cell transcriptomic and spatial multiplex immunofluorescence analyses, we show that PD-L1+ TAMs are mature and immunostimulatory with spatial preference to T cells. In contrast, PD-L1- TAMs are immunosuppressive and spatially co-localize with cancer cells. Either higher density of PD-L1+ TAMs alone or ratio of PD-L1+/PD-L1- TAMs correlate with favorable clinical outcome in two independent cohorts of patients with breast cancer. Mechanistically, we show that PD-L1 is upregulated during the monocyte-to-macrophage maturation and differentiation process and does not require external IFN-γ stimulus. Functionally, PD-L1+ TAMs are more mature/activated and promote CD8+ T cells proliferation and cytotoxic capacity. Together, our findings reveal insights into the immunological significance of PD-L1 within the TIME.


Asunto(s)
Neoplasias de la Mama , Macrófagos Asociados a Tumores , Humanos , Femenino , Macrófagos Asociados a Tumores/metabolismo , Neoplasias de la Mama/metabolismo , Antígeno B7-H1/genética , Linfocitos T CD8-positivos/metabolismo , Macrófagos , Microambiente Tumoral
19.
Opt Express ; 32(3): 3123-3137, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38297541

RESUMEN

This study investigates the thermal compensation mechanism in dual-mode Si3N4 microresonators that demonstrates the ease of generation of single-solitons with nearly octave-wide spectral bandwidth. The deterministic creation of soliton frequency combs is achieved by merely switching the wavelength of a tunable laser or a semiconductor diode laser in a single step. The pump frequency detuning range that can sustain the soliton state is 30 gigahertz (GHz), which is approximately 100 times the resonance linewidth. Interestingly, these dual-mode resonators also support the coexistence of primary combs and solitons, enabling their utilization as functional microwave synthesizers. Furthermore, these resonators readily facilitate the generation of diverse multi-solitons and soliton crystals. This work presents a simplified system to access high-performance and versatile Kerr solitons, with wide-ranging applications in optical metrology, microwave photonics, and LiDAR.

20.
Qual Life Res ; 33(3): 817-829, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38167749

RESUMEN

PURPOSE: To develop the mapping functions from the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) scores onto the EQ-5D-5L and SF-6Dv2 utility values among the overweight and obese population in China. METHODS: A representative sample of the overweight and obese population in China stratified by age, sex, body mass index (BMI), and area of residence was collected by online survey and the sample was randomly divided into development (80%) and validation (20%) datasets. The conceptual overlap between the IWQOL-Lite and the EQ-5D-5L or SF-6Dv2 was evaluated by Spearman's correlation coefficients. Five models, including OLS, Tobit, CLAD, GLM, and PTM were explored to derive mapping functions using the development dataset. The model performance was assessed using MAE, RMSE, and the percentage of AE > 0.05 and AE > 0.1 in the validation dataset. RESULTS: A total of 1000 respondents (48% female; mean [SD] age: 51.7 [15.3]; mean [SD] BMI: 27.4 [2.8]) were included in this study. The mean IWQOL-Lite scores and the utility values of EQ-5D-5L and SF-6Dv2 were 78.5, 0.851, and 0.734, respectively. The best-performing models predicting EQ-5D-5L and SF-6Dv2 utilities both used IWQOL-Lite total score as a predictor in the CLAD model (MAE: 0.083 and 0.076 for the EQ-5D-5L and SF-6Dv2; RMSE: 0.125 and 0.103 for the EQ-5D-5L and SF-6Dv2; AE > 0.05: 20.5% and 27.5% for the EQ-5D-5L and SF-6Dv2; AE > 0.10: 9.5% and 15.0% for the EQ-5D-5L and SF-6Dv2). CONCLUSION: CLAD models with the IWQOL-Lite total score can be used to predict both the EQ-5D-5L and SF-6Dv2 utility values among overweight and obese population in China.


Asunto(s)
Sobrepeso , Calidad de Vida , Humanos , Femenino , Persona de Mediana Edad , Masculino , Calidad de Vida/psicología , Encuestas y Cuestionarios , China , Obesidad
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