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1.
Opt Lett ; 49(11): 3130-3133, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824345

RESUMEN

Improving the conversion efficiency is particularly important for the generation and applications of harmonic waves in optical microstructures. Herein, we propose to enhance the efficiency of third harmonic generation by integrating a monolayer WS2 with the metal/dielectric/photonic crystal multilayer structure. The numerical simulations show that the multilayer structure enables to generate the Tamm plasmon mode between the metal film and photonic crystal around the telecommunication wavelength, which is consistent with the experimental result. By measuring with a self-built nonlinear optical micro-spectroscopy system, we find that the third harmonic signal can be reinforced by 16-fold through inserting the monolayer WS2 in the dielectric spacer. This work will provide a new way for improving nonlinear optical response, especially THG in multilayer photonic microstructures.

2.
Front Plant Sci ; 15: 1371040, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38742213

RESUMEN

Introduction: Clonal fragmentation helps to assess clonal plants' growth resilience to human and environmental disturbance. Although clonal integration in epiphytes in tropical rubber plantations is important to understand their role in enhancing biodiversity and ecosystem services, research on this subject is limited. These plantations are typically monospecific economic forests that face increased anthropogenic disturbances. Methods: In this study, we selected the clonal fern Pyrrosia nuda to study its survival status, biomass, maximum quantum yield of photosystem II (Fv/Fm), and frond length in response to the level of clonal fragmentation in a tropical rubber plantation. Results and discussion: The results showed that (1) clonal fragmentation significantly negatively affected the survival rate, biomass, and frond length of clonal plants, but with minimal effects on Fv/Fm at different growth stages; (2) the performance of a ramet (e.g., biomass or frond length) increased with ramet developmental ages and decreased with the number of ramets in a clonal fragment. The age-dependent impacts of clonal fragmentation provide insights into the biodiversity conservation of epiphytes and forest management in man-made plantations. Therefore, to better conserve the biodiversity in tropical forests, especially in environment-friendly rubber plantations, there is a need to reduce anthropogenic disturbances and alleviate the level of fragmentation.

3.
BMC Palliat Care ; 23(1): 125, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38769557

RESUMEN

BACKGROUND: Few studies have evaluated the perceptions of healthcare providers in China regarding pediatric palliative care, particularly in critical care units (PICUs), where many children receive palliative care. To evaluate the knowledge, attitudes and practices of PICU personnel in China regarding pediatric palliative care. METHODS: This cross-sectional study was conducted in five cities in China (Shanghai, Suzhou, Chongqing, Chengdu and Yunnan) between November 2022 and December 2022. RESULTS: The analysis included 204 participants (122 females), with 158 nurses and 46 physicians. The average knowledge, attitude and practice scores were 9.75 ± 2.90 points (possible range, 0-13 points), 38.30 ± 3.80 points (possible range, 12-60 points) and 35.48 ± 5.72 points (possible range, 9-45 points), respectively. Knowledge score was higher for physicians than for nurses (P < 0.001) and for personnel with previous training in pediatric palliative care (P = 0.005). According to structural equation modelling knowledge had a direct positive effect on attitude (ß = 0.69 [0.28-1.10], p = 0.001), and indirect on practice (ß = 0.82 [0.36-1.28], p < 0.001); attitude had significant effect on practice as well (ß = 1.18 [0.81-1.56], p < 0.001). CONCLUSIONS: There is room for improvement in the knowledge, attitudes and practices of PICU personnel in China regarding pediatric palliative care. The findings of this study may facilitate the design and implementation of targeted education/training programs to better inform physicians and nurses in China about pediatric palliative care.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Cuidados Paliativos , Humanos , Estudios Transversales , Femenino , Masculino , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Cuidados Paliativos/psicología , China , Adulto , Encuestas y Cuestionarios , Persona de Mediana Edad , Personal de Salud/psicología , Personal de Salud/estadística & datos numéricos , Actitud del Personal de Salud , Unidades de Cuidado Intensivo Pediátrico/organización & administración , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Unidades de Cuidados Intensivos/organización & administración , Pediatría/métodos , Pediatría/normas
4.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2597-2606, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38812160

RESUMEN

This study aimed to investigate the role of macrophage polarization in the treatment of liver fibrosis by Fuzheng Huayu Tablets(FZHY) through single-cell, transcriptome sequencing and in vitro and in vivo experiments. Liver fibrosis-related datasets, transcriptomic datasets, and single-cell sequencing datasets were obtained from the Gene Expression Omnibus(GEO) database to screen differential genes. Liver fibrosis-related genes were obtained from GeneCards, DisGeNET, NCBI, PharmgKB, TTD and OMIM databases. Macrophage polarization-related genes were obtained from the GeneCards database. The above three gene sets were intersected to construct a protein-protein interaction(PPI) network. Cytoscape software was used to screen core proteins, and the expression pattern of core proteins was visualized by single-cell sequencing. A mouse model of liver fibrosis was constructed using carbon tetrachloride(CCl_4). Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of liver tissues. The expressions of α-smooth muscle actin(α-SMA) and transforming growth factor-ß1(TGF-ß1) were detected by immunohistochemistry. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by colorimetry. The le-vels of inflammatory factors in serum were detected by the enzyme-linked immunosorbent assay(ELISA). Furthermore, the expressions of α-SMA, TGF-ß1, cluster of differentiation 86(CD86) and thrombospondin 1(THBS1) in liver tissues were detected by Western blot(WB). Lipopolysaccharide(LPS) was used to stimulate RAW264.7 cells to construct the M1 macrophage polarization model. The cell counting kit-8(CCK-8) method was used to detect cell viability. WB was used to detect the protein expressions of CD86 and THBS1 in cells, and the messenger ribonucleic acid(mRNA) expression levels of tumor necrosis factor-α(TNF-α) and interleukin(IL)-1ß by real-time fluorescent quantitative reverse transcription polymerase chain reaction(RT-qPCR). The results showed that a total of 26 potential genes related to the polarization of liver fibrosis macrophages were obtained, and 10 core proteins related to the polarization of liver fibrosis macrophages such as THBS1, lumican(LUM) and fibulin-5(FBLN5) were screened. Single-cell data analysis indicated that THBS1, ranking highest, may be expressed by M1 macrophages. Animal experiments demonstrated that FZHY reduced inflammatory cell infiltration and collagen deposition in CCl_4-induced mouse liver, relieved liver injury and inflammation levels, and inhibited the expressions of α-SMA, TGF-ß1, CD86, and THBS1 proteins. Cell experiments revealed that FZHY significantly reduced intracellular expression of CD86 and THBS1 proteins and mRNA levels of TNF-α and IL-1ß. In conclusion, FZHY may ameliorate liver fibrosis by inhibiting THBS1 protein expression, suppressing M1 macrophage polarization, and reducing inflammation.


Asunto(s)
Medicamentos Herbarios Chinos , Cirrosis Hepática , Transcriptoma , Animales , Medicamentos Herbarios Chinos/farmacología , Ratones , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Transcriptoma/efectos de los fármacos , Masculino , Análisis de la Célula Individual , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo
5.
Huan Jing Ke Xue ; 45(5): 2793-2805, 2024 May 08.
Artículo en Chino | MEDLINE | ID: mdl-38629542

RESUMEN

The purpose of this study was to reveal the spatial and temporal evolution patterns of habitat quality in karst counties of Guizhou plateau and its driving factors and to provide scientific basis for balanced ecological conservation and sustainable development of karst regions. Using DEM data, meteorological data, socio-economic data, and four periods of land use data in 1989, 2003, 2010, and 2020, the InVEST model was used to analyze the spatial and temporal evolution characteristics of habitat quality in Puding County from 1989 to 2020 and to quantitatively detect the driving forces of its spatial divergence. The results were as follows:① Arable land and forest land were the main land use types in Puding County, which constituted the surface cover landscape matrix. Land use changes from 2003-2010 were the most significant, among which forest land had the largest increase of 86.42%; arable land was the most severely lost land use type, with an area decrease of 157.57 km2, mainly flowing to forest land and construction land. ② From 1989 to 2020, the average value of habitat quality index in Puding County increased from 0.60 to 0.73. Spatially, the distribution pattern of "high-low-high" was generally from northeast to southwest, with the high value areas of habitat quality mainly distributed in the woodland and grassland areas in the northeast and the low value areas concentrated in the construction land in the central and south areas. ③ Land use type was the primary factor affecting the spatial and temporal distribution of habitat quality, with an explanation of 91.00%. In the interaction detection, the interaction of any two influencing factors was greater than that of individual factors alone, and the interaction between land use type and average annual precipitation was the strongest, reaching 96.00%; the interaction with lithological factors reached 94.00%, with natural and human factors jointly dominating the spatial and temporal changes in habitat quality. From the results of this study, we concluded that the habitat quality of Puding County was generally good from 1989 to 2020, and the relationship between land use type changes and habitat quality was close. Optimizing the land use structure and reducing the influence of human activities are important to improve the habitat quality of Puding County.

6.
Molecules ; 29(7)2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38611742

RESUMEN

Tumor vaccines have been considered a promising therapeutic approach for treating cancer in recent years. With the development of sequencing technologies, tumor vaccines based on neoantigens or genomes specifically expressed in tumor cells, mainly in the form of peptides, nucleic acids, and dendritic cells, are beginning to receive widespread attention. Therefore, in this review, we have introduced different forms of neoantigen vaccines and discussed the development of these vaccines in treating cancer. Furthermore, neoantigen vaccines are influenced by factors such as antigen stability, weak immunogenicity, and biosafety in addition to sequencing technology. Hence, the biological nanomaterials, polymeric nanomaterials, inorganic nanomaterials, etc., used as vaccine carriers are principally summarized here, which may contribute to the design of neoantigen vaccines for improved stability and better efficacy.


Asunto(s)
Vacunas contra el Cáncer , Nanoestructuras , Neoplasias , Ácidos Nucleicos , Humanos , Vacunas contra el Cáncer/uso terapéutico , Medicina de Precisión , Nanoestructuras/uso terapéutico , Neoplasias/terapia
7.
Chem Sci ; 15(16): 5973-5979, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38665518

RESUMEN

Supramolecular engineering is exceptionally appealing in the design of functional materials, and J-aggregates resulting from noncovalent interactions offer intriguing features. However, building J-aggregation platforms remains a significant challenge. Herein, we report 3,5-dithienyl Aza-BODIPYs with a donor-acceptor-donor (D-A-D) architecture as the first charge transfer (CT)-coupled J-aggregation BODIPY-type platform. The core acceptor moieties in one molecule interact with donor units in neighboring molecules to generate slip-stacked packing motifs, resulting in CT-coupled J-aggregation with a redshifted wavelength up to 886 nm and an absorption tail over 1100 nm. The J-aggregates show significant photoacoustic signals and high photothermal conversion efficiency of 66%. The results obtained in vivo show that the J-aggregates have the potential to be used for tumor photothermal ablation and photoacoustic imaging. This study not only demonstrates Aza-BODIPY with D-A-D as a novel CT-coupled J-aggregation platform for NIR phototherapy materials but also motivates further study on the design of J-aggregation.

8.
Small ; : e2402430, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38623987

RESUMEN

The electronic states of metal catalysts can be redistributed by the rectifying contact between metal and semiconductor e.g., N-doped carbon (NC), while the interfacial regulation degree is very limited. Herein, a deep electronic state regulation is achieved by constructing a novel double-heterojunctional Co/Co3O4@NC catalyst containing Co/Co3O4 and Co3O4/NC heterojunctions. When used for dilute electrochemical NO3 - reduction reaction (NO3RR), the as-prepared Co/Co3O4@NC exhibits an outstanding Faradaic efficiency for NH3 formation (FENH3) of 97.9%, -0.4 V versus RHE and significant NH3 yield of 303.5 mmol h-1 gcat -1 at -0.6 V at extremely low nitrate concentrations (100 ppm NO3 --N). Experimental and theoretical results reveal that the dual junctions of Co/Co3O4 and Co3O4/NC drive a unidirectional electron transfer from Co to NC (Co→Co3O4→NC), resulting in electron-deficient Co atoms. The electron-deficient Co promotes NO3 - adsorption, the rate-determining step (RDS) for NO3RR, facilitating the dilute NO3RR to NH3. The design strategy provides a novel reference for unidirectional multistage regulation of metal electronic states boosting electrochemical dilute NO3RR, which opens up an avenue for deep electronic state regulation of electrocatalyst breaking the limitation of the electronic regulation degree by rectifying contact.

9.
Exp Neurol ; 377: 114777, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38636772

RESUMEN

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) is a devastating acute cerebrovascular event with high mortality and permanent disability rates. Higher galectin-3 levels on days 1-3 have been shown to predict the development of delayed cerebral infarction or adverse outcomes after SAH. Recent single-cell analysis of microglial transcriptomic diversity in SAH revealed that galectin could influence the development and course of neuroinflammation after SAH. METHODS: This study aimed to investigate the role and mechanism of galectin-3 in SAH and to determine whether galectin-3 inhibition prevents early brain injury by reducing microglia polarization using a mouse model of SAH and oxyhemoglobin-treated activation of mouse BV2 cells in vitro. RESULTS: We found that the expression of galectin-3 began to increase 12 h after SAH and continued to increase up to 72 h. Importantly, TD139-inhibited galectin-3 expression reduced the release of inflammatory factors in microglial cells. In the experimental SAH model, TD139 treatment alleviated neuroinflammatory damage after SAH and improved defects in neurological functions. Furthermore, we demonstrated that galectin-3 inhibition affected the activation and M1 polarization of microglial cells after SAH. TD139 treatment inhibited the expression of TLR4, p-NF-κB p65, and NF-κB p65 in microglia activated by oxyhemoglobin as well as eliminated the increased expression and phosphorylation of JAK2 and STAT3. CONCLUSION: These findings suggest that regulating microglia polarization by galectin-3 after SAH to improve neuroinflammation may be a potential therapeutic target.


Asunto(s)
Galectina 3 , Ratones Endogámicos C57BL , Microglía , Enfermedades Neuroinflamatorias , Hemorragia Subaracnoidea , Animales , Microglía/metabolismo , Microglía/efectos de los fármacos , Galectina 3/metabolismo , Galectina 3/antagonistas & inhibidores , Ratones , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/metabolismo , Hemorragia Subaracnoidea/patología , Enfermedades Neuroinflamatorias/etiología , Enfermedades Neuroinflamatorias/metabolismo , Masculino , Lesiones Encefálicas/etiología , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología
10.
Cell ; 187(11): 2717-2734.e33, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38653239

RESUMEN

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as ß-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.


Asunto(s)
Akkermansia , Bacteroides , Ácidos y Sales Biliares , Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Simbiosis , Animales , Humanos , Masculino , Ratones , Akkermansia/metabolismo , Bacteroides/metabolismo , beta-Lactamasas/metabolismo , Ácidos y Sales Biliares/metabolismo , Vías Biosintéticas/genética , Hígado Graso/metabolismo , Hígado/metabolismo , Ratones Endogámicos C57BL , Verrucomicrobia/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/microbiología
11.
Chem Soc Rev ; 53(8): 3976-4019, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38450547

RESUMEN

Mitochondria are essential for a diverse array of biological functions. There is increasing research focus on developing efficient tools for mitochondria-targeted detection and treatment. BODIPY dyes, known for their structural versatility and excellent spectroscopic properties, are being actively explored in this context. Numerous studies have focused on developing innovative BODIPYs that utilize optical signals for imaging mitochondria. This review presents a comprehensive overview of the progress made in this field, aiming to investigate mitochondria-related biological events. It covers key factors such as design strategies, spectroscopic properties, and cytotoxicity, as well as mechanism to facilitate their future application in organelle imaging and targeted therapy. This work is anticipated to provide valuable insights for guiding future development and facilitating further investigation into mitochondria-related biological sensing and phototherapy.


Asunto(s)
Compuestos de Boro , Colorantes Fluorescentes , Mitocondrias , Fotoquimioterapia , Compuestos de Boro/química , Compuestos de Boro/farmacología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Humanos , Colorantes Fluorescentes/química , Animales , Imagen Óptica , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología
12.
Front Neurosci ; 18: 1364338, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38486967

RESUMEN

In clinical practice and research, the classification and diagnosis of neurological diseases such as Parkinson's Disease (PD) and Multiple System Atrophy (MSA) have long posed a significant challenge. Currently, deep learning, as a cutting-edge technology, has demonstrated immense potential in computer-aided diagnosis of PD and MSA. However, existing methods rely heavily on manually selecting key feature slices and segmenting regions of interest. This not only increases subjectivity and complexity in the classification process but also limits the model's comprehensive analysis of global data features. To address this issue, this paper proposes a novel 3D context-aware modeling framework, named 3D-CAM. It considers 3D contextual information based on an attention mechanism. The framework, utilizing a 2D slicing-based strategy, innovatively integrates a Contextual Information Module and a Location Filtering Module. The Contextual Information Module can be applied to feature maps at any layer, effectively combining features from adjacent slices and utilizing an attention mechanism to focus on crucial features. The Location Filtering Module, on the other hand, is employed in the post-processing phase to filter significant slice segments of classification features. By employing this method in the fully automated classification of PD and MSA, an accuracy of 85.71%, a recall rate of 86.36%, and a precision of 90.48% were achieved. These results not only demonstrates potential for clinical applications, but also provides a novel perspective for medical image diagnosis, thereby offering robust support for accurate diagnosis of neurological diseases.

13.
Opt Lett ; 49(6): 1453-1456, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489423

RESUMEN

Surface plasmon resonance holographic microscopy (SPRHM) has been employed to measure the refractive index but whose performance is generally limited by the metallic intrinsic loss. Herein we first, to our knowledge, utilize guided wave resonance (GWR) with low loss to realize the monitoring of the refractive index by integrating with digital holographic microscopy (DHM). By depositing a dielectric layer on a silver film, we observe a typical GWR in the dielectric layer with stronger field enhancement and higher sensitivity to the surrounding refractive index compared to the silver film-supported SPR, which agrees well with calculations. The innovative combination of the GWR and DHM contributes to the highly sensitive dynamic monitoring of the surrounding refractive index variation. Through the measurement with DHM, we found that the GWR presents an excellent sensitivity, which is 2.6 times higher than that of the SPR on the silver film. The results will pave a new pathway for digital holographic interferometry and its applications in environmental and biological detections.

14.
World Neurosurg ; 184: e613-e632, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38367857

RESUMEN

BACKGROUND: Stem cells have shown tremendous potential and vast prospects in the research of intervertebral disc (IVD) regeneration and repair, attracting considerable attention in recent years. In this study, a bibliometric analysis and visualization techniques were employed to probe and analyze the hotspots and frontiers of stem cell research in IVD regeneration and repair, aiming to provide valuable references and insights for further investigations. METHODS: This study utilized the Science Citation Index Expanded from the Web of Science Core Collection database to retrieve and extract relevant literature records as research samples. Visual analysis tools such as VOSviewer 1.6.19, CiteSpace 6.2.R4, and bibliometric online analysis platforms were employed to construct scientific knowledge maps, providing a comprehensive and systematic exposition from various perspectives including collaboration networks, cocitation networks, and co-occurrence networks. RESULTS: A total of 1075 relevant studies have been published in 303 journals by 4181 authors from 1198 institutions across 54 countries/regions. Over the past 20 years, the field of research has witnessed a significant growth in annual publications and citations. China and the United States have emerged as the primary participants and contributors, with the AO Research Institute Davos, Zhejiang University, and Tokai University being the top 3 leading research institutions. The most productive and highly cited author is Sakai D, who is regarded as a key leader in this research field. The journals with the highest number of publications and citations are Spine and Biomaterials, which are considered to be high-quality and authoritative core journals in this field. The current research focuses primarily on the sources and selection of stem cells, optimization of transplantation strategies, mechanisms of IVD regeneration, and the combined application of stem cells and biomaterials. However, there are still some challenges that need to be addressed, including posttransplantation stability, assessment of regenerative effects, and translation into clinical applications. Future research will concentrate on the diversity of stem cell sources, the application of novel biomaterials, personalized treatments, and the development of gene editing technologies, among other cutting-edge directions. CONCLUSIONS: This study utilized bibliometric analysis and visualization techniques to unveil the hotspots and frontiers in the research on stem cells for IVD regeneration and repair. These research findings provide essential guidance and references for further experimental design and clinical applications. However, additional experiments and clinical studies are still needed to address the challenges and difficulties faced in the field of IVD regeneration and repair, thus offering novel strategies and approaches for the treatment of IVD diseases.


Asunto(s)
Disco Intervertebral , Investigación con Células Madre , Humanos , Bibliometría , Materiales Biocompatibles , Regeneración
15.
J Am Chem Soc ; 146(8): 5678-5692, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38359327

RESUMEN

The rapid and controlled synthesis of high-molecular-weight (HMW) polysarcosine (pSar), a potential polyethylene glycol (PEG) alternative, via the ring-opening polymerization (ROP) of N-carboxyanhydride (NCA) is rare and challenging. Here, we report the well-controlled ROP of sarcosine NCA (Sar-NCA) that is catalyzed by various carboxylic acids, which accelerate the polymerization rate up to 50 times, and enables the robust synthesis of pSar with an unprecedented ultrahigh molecular weight (UHMW) up to 586 kDa (DP ∼ 8200) and exceptionally narrow dispersity (D̵) below 1.05. Mechanistic experiments and density functional theory calculations together elucidate the role of carboxylic acid as a bifunctional catalyst that significantly facilitates proton transfer processes and avoids charge separation and suggest the ring opening of NCA, rather than decarboxylation, as the rate-determining step. UHMW pSar demonstrates improved thermal and mechanical properties over the low-molecular-weight counterparts. This work provides a simple yet highly efficient approach to UHMW pSar and generates a new fundamental understanding useful not only for the ROP of Sar-NCA but also for other NCAs.

16.
Sci Rep ; 14(1): 3901, 2024 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-38365809

RESUMEN

Disulfidptosis is a condition where dysregulated NAPDH levels and abnormal accumulation of cystine and other disulfides occur in cells with high SLC7A11 expression under glucose deficiency. This disrupts normal formation of disulfide bonds among cytoskeletal proteins, leading to histone skeleton collapse and triggering cellular apoptosis. However, the correlation between disulfidptosis and immune responses in relation to glioblastoma survival rates and immunotherapy sensitivity remains understudied. Therefore, we utilized The Cancer Genome Atlas and The Chinese Glioma Genome Atlas to identify disulfidptosis-related immune checkpoint genes and established an overall survival (OS) prediction model comprising six genes: CD276, TNFRSF 14, TNFSF14, TNFSF4, CD40, and TNFRSF18, which could also be used for predicting immunotherapy sensitivity. We identified a cohort of glioblastoma patients classified as high-risk, which exhibited an upregulation of angiogenesis, extracellular matrix remodeling, and epithelial-mesenchymal transition as well as an immunosuppressive tumor microenvironment (TME) enriched with tumor associated macrophages, tumor associated neutrophils, CD8 + T-cell exhaustion. Immunohistochemical staining of CD276 in 144 cases further validated its negative correlation with OS in glioma. Disulfidptosis has the potential to induce chronic inflammation and an immunosuppressive TME in glioblastoma.


Asunto(s)
Glioblastoma , Glioma , Humanos , Glioblastoma/genética , Glioblastoma/terapia , Microambiente Tumoral/genética , Pronóstico , Factores de Transcripción , Apoptosis , Ligando OX40 , Antígenos B7
17.
J Am Chem Soc ; 146(6): 3974-3983, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38299512

RESUMEN

Biologics, including proteins and antisense oligonucleotides (ASOs), face significant challenges when it comes to achieving intracellular delivery within specific organs or cells through systemic administrations. In this study, we present a novel approach for delivering proteins and ASOs to liver cells, both in vitro and in vivo, using conjugates that tether N-acetylated galactosamine (GalNAc)-functionalized, cell-penetrating polydisulfides (PDSs). The method involves the thiol-bearing cargo-mediated ring-opening polymerization of GalNAc-functionalized lipoamide monomers through the so-called aggregation-induced polymerization, leading to the formation of site-specific protein/ASO-PDS conjugates with narrow dispersity. The hepatocyte-selective intracellular delivery of the conjugates arises from a combination of factors, including first GalNAc binding with ASGPR receptors on liver cells, leading to cell immobilization, and the subsequent thiol-disulfide exchange occurring on the cell surface, promoting internalization. Our findings emphasize the critical role of the close proximity of the PDS backbone to the cell surface, as it governs the success of thiol-disulfide exchange and, consequently, cell penetration. These conjugates hold tremendous potential in overcoming the various biological barriers encountered during systemic and cell-specific delivery of biomacromolecular cargos, opening up new avenues for the diagnosis and treatment of a range of liver-targeting diseases.


Asunto(s)
Productos Biológicos , Galactosamina , Galactosamina/química , Hepatocitos/metabolismo , Oligonucleótidos Antisentido/química , Disulfuros/metabolismo , Compuestos de Sulfhidrilo/metabolismo , Productos Biológicos/metabolismo
19.
Clin Neurol Neurosurg ; 236: 108111, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38199117

RESUMEN

OBJECTIVES: The purpose of this study was to evaluate the effectiveness of endoscopic endonasal surgery (EES) for Rathke's cleft cysts (RCCs) and the advantages of detailed preoperative imaging evaluation, intraoperative personalized removal and multilevel sellar floor reconstruction. METHODS: The clinical data of 43 patients with RCCs who were treated by EES in the neurosurgery department of affiliated hospital of Jiangnan University and Wuxi No.2 People's Hospital from January 2018 to January 2023 were retrospectively analyzed. The effectiveness of EES for RCCs was analyzed by imaging information, surgical procedures, symptom improvement and complications. RESULTS: All 43 RCCs were completely removed by EES, and all clinical symptoms improved to varying degrees. Postoperative relief of headache was achieved in 23 out of 26 patients (88.5 %); there was improvement in 10 out of 13 patients with visual field disorders (76.9 %) and in 8 out of 10 patients with endocrine abnormalities (80 %). New hormonal deficiency was discovered in 7 of all the patients postoperatively. There were 8 patients with postoperative diabetes insipidus and 1 patient with cerebrospinal fluid leakage. The incidence of new hormonal dysfunction and postoperative DI in expanded EES (33.3 %, 33.3 %) was higher than it in conventional EES (4 %, 8 %) (P < 0.05). The average follow-up time was 29.1 ± 14.8 months, and there were no deaths or infections. Three patients presented with cyst recurrence on MRI. CONCLUSIONS: The clinical manifestations and imaging characteristics of RCCs are variable, and a detailed preoperative review of the imaging is helpful for the development of surgical plans. RCCs can be treated more safely and thoroughly with less trauma and complications by intraoperative personalized removal and multilevel sellar floor reconstruction. The high incidence of new hormonal dysfunction and postoperative DI may be related to the disturbance of the pituitary stalk. EES has unique advantages and high clinical application value for the treatment of RCCs.


Asunto(s)
Quistes del Sistema Nervioso Central , Quistes , Neoplasias Hipofisarias , Humanos , Estudios Retrospectivos , Quistes del Sistema Nervioso Central/diagnóstico por imagen , Quistes del Sistema Nervioso Central/cirugía , Quistes del Sistema Nervioso Central/complicaciones , Endoscopía , Quistes/complicaciones , Hipófisis/diagnóstico por imagen , Hipófisis/cirugía , Neoplasias Hipofisarias/cirugía
20.
Res Sq ; 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38260302

RESUMEN

Tripartite motif-containing protein 26 (TRIM26) is an E3 ubiquitin ligase that exhibits divergent roles in various cancer types (oncogenic and anti-oncogenic). This study investigates the interaction of TRIM26 with the tumor suppressor protein p53 in colorectal cancer (CRC) cells by performing a comprehensive set of biochemical, cell-based assays, and xenograft experiments. As a result, we found that overexpression of TRIM26 significantly enhances CRC cell proliferation and colony formation, while knockdown of TRIM26 suppresses these processes. Xenograft experiments further validated the tumor-promoting role of TRIM26 in CRC. Supporting this is that TRIM26 is highly expressed in human CRC tissues as revealed by our analysis of the TCGA database. Biochemically, TRIM26 directly bound to the C-terminus of p53 and facilitated its ubiquitination, resulting in proteolytic degradation and attenuated p53 activity independently of MDM2. Also, TRIM26 increased the MDM2-mediated ubiquitination of p53 by binding to MDM2's C-terminus. This study uncovers the oncogenic potential of TRIM26 in CRC by inhibiting p53 function. Through its ubiquitin ligase activity, TRIM26 destabilizes p53, consequently promoting CRC cell proliferation and tumor growth. These findings shed light on the complex involvement of TRIM26 in cancer and identify this ubiquitin ligase as a potential therapeutic target for future development of CRC treatment.

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