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1.
Bioengineering (Basel) ; 11(10)2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39451393

RESUMO

Wound healing is a complex and precisely regulated process that encompasses multiple stages, including inflammation, anti-inflammation, and tissue repair. It involves various cells and signaling molecules, with macrophages demonstrating a significant degree of plasticity and playing a crucial regulatory role at different stages. In recent years, the use of biomaterials, which include both natural and synthetic polymers or macromolecules, has proliferated for the purpose of enhancing wound healing. This review summarizes how these diverse biomaterials promote wound healing by modulating macrophage behavior and examines the broader implications of these modulations. Additionally, we discuss the limitations associated with the clinical application of immunomodulatory biomaterials and propose potential solutions. Finally, we look towards future developments in the design of immunomodulatory biomaterials intended to enhance wound healing.

2.
Mol Neurodegener ; 19(1): 77, 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39434125

RESUMO

BACKGROUND: Anti-amyloid-ß (Aß) immunotherapy trials have revealed amyloid-related imaging abnormalities (ARIA) as the most prevalent and serious adverse events linked to pathological changes in cerebral vasculature. Recent studies underscore the critical involvement of perivascular macrophages and the infiltration of peripheral immune cells in regulating cerebrovascular damage. Specifically, Aß antibodies engaged at cerebral amyloid angiopathy (CAA) deposits trigger perivascular macrophage activation and the upregulation of genes associated with vascular permeability. Nevertheless, further research is needed to understand the immediate downstream consequences of macrophage activation, potentially exacerbating CAA-related vascular permeability and microhemorrhages linked to Aß immunotherapy. METHODS: This study investigates immune responses induced by amyloid-targeting antibodies and CAA-induced microhemorrhages using RNA in situ hybridization, histology and digital spatial profiling in an Alzheimer's disease (AD) mouse model of microhemorrhage. RESULTS: In the present study, we have demonstrated that bapineuzumab murine surrogate (3D6) induces profound vascular damage, leading to smooth muscle cell loss and blood-brain barrier (BBB) breakdown. In addition, digital spatial profiling (DSP) reveals that distinct immune responses contribute to vascular damage with peripheral immune responses and perivascular macrophage activation linked to smooth muscle cell loss and vascular fibrosis, respectively. Finally, RNA in situ hybridization identifies two distinct subsets of Trem2+ macrophages representing tissue-resident and monocyte-derived macrophages around vascular amyloid deposits. Overall, these findings highlight multifaceted roles of immune activation and vascular damage in driving the development of microhemorrhage. CONCLUSIONS: In summary, our study has established a significant link between CAA-Aß antibody immune complex formation, immune activation and vascular damage leading to smooth muscle cell loss. However, the full implications of this cascade on the development of microhemorrhages requires further exploration. Additional investigations are warranted to unravel the precise molecular mechanisms leading to microhemorrhage, the interplay of diverse immune populations and the functional roles played by various Trem2+ macrophage populations in response to Aß immunotherapy.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Angiopatia Amiloide Cerebral , Imunoterapia , Animais , Humanos , Camundongos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Anticorpos Monoclonais Humanizados/farmacologia , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Angiopatia Amiloide Cerebral/patologia , Angiopatia Amiloide Cerebral/metabolismo , Hemorragia Cerebral/patologia , Hemorragia Cerebral/metabolismo , Modelos Animais de Doenças , Imunoterapia/métodos , Inflamação/metabolismo , Inflamação/patologia , Camundongos Transgênicos
3.
Small ; : e2405496, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291904

RESUMO

Specifically controlling cell pyroptosis is advantageous for oncotherapy as it allows simultaneous ablation of primary tumors and activation of immunogenicity of tumor environment. Herein, a facile and robust strategy is presented to construct efficient NIR-activated helical pyroptosis agents (PyroAs) with negligible dark cytotoxicity. It is demonstrated that the construction of four intramolecular B-X bonds (X = O or N) within the BODIPY chromophore enforces a significant twisting of its π-conjugation, yielding a variety of helical HBD molecules with desired high photosensitivity and negligible dark toxicity. A robust approach is established to extend HBD into the near-infrared (NIR) region through site-selective incorporation of an electron-withdrawing ester moiety. It is also proved that targeted delivery of the NIR-activated HBD-ER to the endoplasmic reticulum (ER) specifically activates pyroptosis pathway by equipping it with an ER-targeting moiety. Finally, the favorable biocompatibility, excellent antitumor efficacy, and remarkable systematic immune response of this unique NIR-activated helical PyroAs are shown in vivo, demonstrating its potential application in solid tumor immunotherapy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39250358

RESUMO

In recent years, vision-centric Bird's Eye View (BEV) perception has garnered significant interest from both industry and academia due to its inherent advantages, such as providing an intuitive representation of the world and being conducive to data fusion. The rapid advancements in deep learning have led to the proposal of numerous methods for addressing vision-centric BEV perception challenges. However, there has been no recent survey encompassing this novel and burgeoning research field. To catalyze future research, this paper presents a comprehensive survey of the latest developments in vision-centric BEV perception and its extensions. It compiles and organizes up-to-date knowledge, offering a systematic review and summary of prevalent algorithms. Additionally, the paper provides in-depth analyses and comparative results on various BEV perception tasks, facilitating the evaluation of future works and sparking new research directions. Furthermore, the paper discusses and shares valuable empirical implementation details to aid in the advancement of related algorithms.

5.
J Appl Biomater Funct Mater ; 22: 22808000241266487, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39129376

RESUMO

Despite advancements in therapeutic techniques, restoring bone tissue after damage remains a challenging task. Tissue engineering or targeted drug delivery solutions aim to meet the pressing clinical demand for treatment alternatives by creating substitute materials that imitate the structural and biological characteristics of healthy tissue. Polymers derived from natural sources typically exhibit enhanced biological compatibility and bioactivity when compared to manufactured polymers. Chitosan is a unique polysaccharide derived from chitin through deacetylation, offering biodegradability, biocompatibility, and antibacterial activity. Its cationic charge sets it apart from other polymers, making it a valuable resource for various applications. Modifications such as thiolation, alkylation, acetylation, or hydrophilic group incorporation can enhance chitosan's swelling behavior, cross-linking, adhesion, permeation, controllable drug release, enzyme inhibition, and antioxidative properties. Chitosan scaffolds possess considerable potential for utilization in several biological applications. An intriguing application is its use in the areas of drug distribution and bone tissue engineering. Due to their excellent biocompatibility and lack of toxicity, they are an optimal material for this particular usage. This article provides a comprehensive analysis of osteoporosis, including its pathophysiology, current treatment options, the utilization of natural polymers in disease management, and the potential use of chitosan scaffolds for drug delivery systems aimed at treating the condition.


Assuntos
Quitosana , Osteoporose , Alicerces Teciduais , Quitosana/química , Humanos , Osteoporose/tratamento farmacológico , Alicerces Teciduais/química , Engenharia Tecidual , Animais , Sistemas de Liberação de Medicamentos , Materiais Biocompatíveis/química
6.
ACS Appl Mater Interfaces ; 16(30): 39064-39078, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39028896

RESUMO

The bacterial infection and poor osseointegration of Ti implants could significantly compromise their applications in bone repair and replacement. Based on the carrier separation ability of the heterojunction and the redox reaction of pseudocapacitive metal oxides, we report an electrically responsive TiO2-SnO2-RuO2 coating with a multilayered heterostructure on a Ti implant. Owing to the band gap structure of the TiO2-SnO2-RuO2 coating, electron carriers are easily enriched at the coating surface, enabling a response to the endogenous electrical stimulation of the bone. With the formation of SnO2-RuO2 pseudocapacitance on the modified surface, the postcharging mode can significantly change the surface chemical state of the coating due to the redox reaction, enhancing the antibacterial ability and osteogenesis-related gene expression of the human bone marrow mesenchymal stem cells. Owing to the attraction for Ca2+, only the negatively postcharged SnO2@RuO2 can promote apatite deposition. The in vivo experiment reveals that the S-SnO2@RuO2-NP could effectively kill the bacteria colonized on the surface and promote osseointegration with the synostosis bonding interface. Thus, negatively charging the electrically responsive coating of TiO2-SnO2-RuO2 is a good strategy to endow modified Ti implants with excellent antibacterial ability and osseointegration.


Assuntos
Antibacterianos , Materiais Revestidos Biocompatíveis , Osseointegração , Compostos de Estanho , Titânio , Titânio/química , Titânio/farmacologia , Osseointegração/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Compostos de Estanho/química , Compostos de Estanho/farmacologia , Animais , Compostos de Rutênio/química , Compostos de Rutênio/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície , Osteogênese/efeitos dos fármacos
7.
Materials (Basel) ; 17(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38893850

RESUMO

Development of high-performance cutting tool materials is one of the critical parameters enhancing the surface finishing of high-speed machined products. Ti(C,N)-based cermets reinforced with and without different contents of silicon nitride were designed and evaluated to satisfy the requirements. In fact, the effect of silicon nitride addition to Ti(C,N)-based cermet remains unclear. The purpose of this study is to investigate the influence of Si3N4 additive on microstructure, mechanical properties, and thermal stability of Ti(C,N)-based cermet cutting tools. In the present work, α-Si3N4 "grade SN-E10" was utilized with various fractions up to 6 wt.% in the designed cermets. A two-step reactive sintering process under vacuum was carried out for the green compact of Ti(C,N)-based cermet samples. The samples with 4 wt.% Si3N4 have an apparent solid density of about 6.75 g/cm3 (relative density of about 98 %); however, the cermet samples with 2 wt.% Si3N4 exhibit a superior fracture toughness of 10.82 MPa.m1/2 and a traverse rupture strength of 1425.8 MPa. With an increase in the contents of Si3N4, the Vickers hardness and fracture toughness of Ti(C,N)-based cermets have an inverse behavior trend. The influence of Si3N4 addition on thermal stability is clarified to better understand the relationship between thermal stability and mechanical properties of Ti(C,N)-based cermets.

8.
Front Oncol ; 14: 1391002, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933447

RESUMO

Objective: To review our single-institution experience in the surgical management of foramen magnum tumors via a far-lateral approach using an oblique straight incision. Methods: From October 2023 to January 2024, four cases of tumors in the foramen magnum area treated at the Capital Medical University-affiliated XuanWu hospital neurosurgery department were involved in this study. All cases were managed with a far-lateral approach using an oblique straight incision. We retrospectively reviewed the clinical and imaging data, as well as the surgical strategies employed. Results: Three cases of foramen magnum meningiomas and one case of glioma of the ventral medulla. All cases underwent a far-lateral approach using an oblique straight incision; all cases had a gross total resection, and the wounds healed well without cerebral fluid leakage or scalp hydrops. Except for one case of right foramen magnum meningioma, which had dysphagia and pneumothorax, the other cases were without any postoperative complications. Conclusion: A far-lateral approach using an oblique straight incision can preserve muscle integrity and minimize subcutaneous exposure, allowing for complete anatomical reduction of muscles. This craniectomy method is simple and replicable, making it worthy of further clinical practice.

9.
Front Neurol ; 15: 1392691, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38813246

RESUMO

Background: Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a rare condition, posing diagnostic and treatment challenges, with histological biopsy essential for diagnosis. Standardized treatment protocols are lacking. This disease requires urgent attention due to the increasing number of organ transplant surgeries and the use of immunosuppressive agents. Methods: From 2020 to 2023, our center diagnosed five patients with PCNS-PTLD. We reviewed their clinical records and conducted a comprehensive analysis of 22 literatures on PCNS-PTLD cases following renal transplantation or allogeneic hematopoietic stem cell transplantation (HSCT). Results: Four patients had previously received a kidney transplant, one had undergone allogeneic HSCT. The median time from the last transplant surgery to the diagnosis of PCNS-PTLD differs between kidney transplant (21.5 years) and allogeneic HSCT (9 months). Common symptoms included motor weakness (n = 4), headache (n = 2), confusion (n = 2), and nausea (n = 2), with ring-enhancing (n = 5), typically solitary (n = 3) and supratentorial (n = 3) lesions on imaging. Diagnosis involved robot-assisted stereotactic brain biopsy (n = 4) or craniotomy (n = 1), all showing Epstein-Barr virus and CD20 positivity. Most cases (n = 4) were monomorphic diffuse large B-cell lymphoma. Treatment included rituximab (n = 3), surgical resection (n = 2), zanubrutinib (n = 1), whole-brain radiation (n = 1), and methotrexate (n = 1). At the last follow-up, the median duration of follow-up for all patients was 19 months. During this time, 3 patients had died and 2 patients were still alive. Conclusion: In patients with a history of kidney transplantation or allogeneic HSCT who are on long-term immunosuppressive therapy, any neurological symptoms, particularly the presence of supratentorial ring-enhancing masses in the brain on imaging, whether solitary or multiple, should raise high suspicion for this disease, warranting a timely brain biopsy. Additionally, we found that besides reducing immunosuppressants, zanubrutinib may be a potential, safe, and effective treatment for this condition. Moreover, post-surgical administration of rituximab in conjunction with whole-brain radiotherapy also appears to be a potentially safe and effective approach.

10.
Polymers (Basel) ; 16(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38475323

RESUMO

In order to solve the problem of excessive consumption of petrochemical resources and the harm of free formaldehyde release to human health, biomass raw materials, such as sucrose (S) and ammonium dihydrogen phosphate (ADP) can be chemically condensed in a simple route under acidic conditions to produce a formaldehyde free wood adhesive (S-ADP), characterized by good storage stability and water resistance, and higher wet shear strength with respect to petroleum based phenolic resin adhesive. The dry and boiling shear strength of the plywood based on S-ADP adhesive are as high as 1.05 MPa and 1.19 MPa, respectively. Moreover, is Modulus of Elasticity (MOE) is as high as 4910 MPa. Interestingly, the plywood based on the developed S-ADP adhesive exhibited good flame retardancy. After burning for 90 s, its shape remains unchanged. Meanwhile, it can be concluded from thermomechanical analysis (TMA) and thermogravimetric analysis (TGA) that the S-ADP acquired excellent modulus of elasticity (MOE) and good thermal stability. It is thus thought promisingly that the use of S-ADP adhesive as a substitute for PF resin adhesive seems feasible in the near future.

11.
J Am Soc Mass Spectrom ; 35(4): 674-682, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38416724

RESUMO

False changes discovered by quantitative proteomics reduce the trust of biologists in proteomics and limit the applications of proteomics to unlock biological mechanisms, which suppresses the application of proteomics techniques in the pharmaceutical industry more than it does in academic research. To remove false changes that arise during LC-MS/MS data acquisition, we evaluated the contributions of peptide abundance and number of unique peptides on reproducibility. Lower abundance and only one unique peptide have a higher risk of generating a higher coefficient of variation (CV), resulting in less accurate quantification. However, the abundance of peptides in samples is not adjustable and discarding proteins quantified by only one unique peptide is not a choice either. Indeed, a large percentage of proteins are accurately quantified by only one unique peptide. Therefore, to improve the calculations of the CV, we leverage a new function in PEAKS called QC-channels which enables technical replicates of each spectrum to be evaluated prior to calculation of the CV. While the QC-channels function in PEAKS significantly reduced the false quantification, random false changes still exist due to known or unknown reasons. To address this challenge, we present the idea of Trend-design to track trend changes rather than changes from two points to remove false quantifications and reveal consequential changes responding to a treatment or condition. The idea was confirmed by molecules with different affinity and dose in the current study. The combination of QC-channels and Trend-design enables a more impactful quantitative proteomics to allow unlocking biological mechanisms using proteomics.


Assuntos
Proteômica , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Proteômica/métodos , Reprodutibilidade dos Testes , Proteínas , Peptídeos/química
12.
ACS Appl Mater Interfaces ; 16(5): 6250-6260, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38284410

RESUMO

Thin, flexible, and electrically conductive films are in demand for electromagnetic interference (EMI) shielding. Two-dimensional NbSe2 monolayers have an electrical conductivity comparable to those of metals (106-107 S m-1) but are challenging for high-quality and scalable production. Here, we show that electrochemical exfoliation of flake NbSe2 powder produces monolayers on a large scale (tens of grams), at a high yield (>75%, monolayer), and with a large average lateral size (>20 µm). The as-exfoliated NbSe2 monolayer flakes are easily dispersed in diverse organic solvents and solution-processed into various macroscopic structures (e.g., free-standing films, coatings, patterns, etc.). Thermal annealing of the free-standing NbSe2 films reduces the interlayer distance of restacked NbSe2 from 1.18 to 0.65 nm and consequently enhances the electrical conductivity to 1.16 × 106 S m-1, which is superior to those of MXenes and reduced graphene oxide. The optimized NbSe2 film shows an EMI shielding effectiveness (SE) of 65 dB at a thickness of 5 µm (>110 dB for a 48-µm-thick film), among the highest in materials of similar thicknesses. Moreover, a laminate of two layers of the NbSe2 film (2 µm thick) with an insulating interlayer shows a high SE of 85 dB, surpassing that of the 20-µm-thick NbSe2 film (83 dB). A two-layer theoretical model is proposed, and it agrees with the experimental EMI SE of the laminated NbSe2 films. The ability to produce NbSe2 monolayers on a tens of grams scale will enable their diverse applications beyond EMI shielding.

13.
J Colloid Interface Sci ; 658: 772-782, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38154240

RESUMO

Aerogels with 3D porous structures have been attracting increasing attention among functional materials due to their advantages of being lightweight and high specific surface area. Precise control of the porous structure of aerogel is essential to improve its performance. In this work, polylactic acid (PLA) aerogels with distinctly different microstructures were fabricated by precisely controlling the phase separation behavior of the ternary solution system. Rheological and theoretical analyses have revealed that the interactions between polymer molecules, solvents and non-solvents play a crucial role in determining the nucleation and growth of poor olymer and rich polymer phases. By adjusting the non-solvent type and the solution composition, aerogels with spider network structure, bead-like connected microsphere structure, and cluster petal structure were obtained. Ideal spinodal phase separation conditions were obtained to produce aerogels with a homogeneous fiber network structure. The optimum PLA aerogel achieved an extremely porosity of 96 % and a high specific surface area of 114 m2/g, which rendered it with excellent triboelectric generation performance. Thus, this work provides fundamental insights into the precise regulation of the phase separation behavior and the structure of the aerogel, which can help boost the performance and expand the applications of PLA aerogels.

15.
Int J Biol Macromol ; 253(Pt 4): 127079, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37769761

RESUMO

Poly(lactic acid) (PLA) is one of the most promising bio-based polyester with great potential to replace for the petroleum-based polymers, which can significantly reduce greenhouse gas emissions. However, the inherent brittleness of PLA seriously restricts its broad applications. Herein, PLA/poly(ε-caprolactone) (PCL)/ethylene methyl acrylate-glycidyl methacrylate (EMA-GMA) ternary blends with different phase structures were prepared through reactive blending. The reactions between the epoxy groups of EMA-GMA and the carboxyl and hydroxyl end groups of PLA and PCL and were evidenced from the Fourier transform infrared spectroscopy, dynamic mechanical analysis and rheological results. The atomic force microscopy (AFM) images clearly revealed the formation of stack structure of the PCL and EMA-GMA minor phases in PLA/PCL/EMA-GMA (80/15/5) blend, and core-shell particle structures in PLA/PCL/EMA-GMA (80/10/10) and (80/5/15) blends. In terms of elongation at break and impact toughness, PLA/PCL/EMA-GMA (80/5/15) blend presents the best properties among all the compositions. Moreover, it also behaved excellent stiffness-toughness balance. The toughening mechanism can be ascribed to the formation of core-shell structure and the existence of interfacial adhesion in the ternary blends. This work can provide guide for the preparation and design of PLA-based partially renewable supertough materials that can compete with conventional petro-derived plastics.


Assuntos
Poliésteres , Polímeros , Poliésteres/química , Polímeros/química , Metacrilatos
16.
Cancer Gene Ther ; 30(12): 1624-1635, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37679528

RESUMO

α-Catenin plays a critical role in tissue integrity, repair, and embryonic development. However, the post-translational modifications of α-catenin and the correlative roles in regulating cancer progression remain unclear. Here, we report that α-catenin is acetylated by p300, and identify three acetylation sites, K45, K866, and K881. Conversely, α-catenin acetylation can be reversed by deacetylase HDAC6. Mechanistically, α-catenin acetylation releases the transcriptional coactivator Yes-associated protein 1 (Yap1) by blocking the interaction between α-catenin and Yap1, and promotes the accumulation of Yap1 in the nucleus. Through this mechanism, acetylation weakens the capacity of α-catenin to inhibit breast cancer cell proliferation and tumor growth in mice. Meanwhile, we show that CDDP induces acetylation of α-catenin, and acetylated α-catenin resists the apoptosis under CDDP conditions. Additionally, acetylation inhibits the proteasome-dependent degradation of α-catenin, thus enhancing the stability of α-catenin for storage. Taken together, our results demonstrate that α-catenin can be acetylated, an event that is key for the subcellular distribution of Yap1 and subsequent facilitation of breast tumorigenesis.


Assuntos
Neoplasias da Mama , beta Catenina , Animais , Camundongos , Acetilação , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , alfa Catenina/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Processamento de Proteína Pós-Traducional , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
Medicine (Baltimore) ; 102(35): e34931, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37657032

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare and special type of non-Hodgkin lymphoma with a significantly worse median overall prognosis than that of non-Hodgkin lymphoma outside the brain. Clarifying the genomic characteristics and alterations in PCNSL could provide clues regarding its distinctive pathophysiology and new treatment options. However, current knowledge about the genomics of PCNSL is limited. In this study, next-generation sequencing (NGS) was performed to investigate the genomic profile of PCNSL. Samples from 12 patients diagnosed with PCNSL at our institution were analyzed for gene mutations using NGS. This study showed that missense mutations were the most common mutation type. C > A/G > T accounted for most of the single-base mutations, which reflected the preference of the tumor sample mutation type and may serve as an important prognostic factor. The most significantly mutated gene was myeloid differentiation factor 88 (MYD88) (0.55), followed by CD79B, LRP1B, and PRDM1 (0.36). None of the cases showed a high tumor mutational burden. In addition to the traditional driver genes, we also identified some new possible ones such as MET, PIM1, and RSBN1L. Enrichment analysis revealed that genes mutated in PCNSL were involved in many pathways and functional protein activities, such as the extracellular matrix and adhesion molecules. The most common genetic alterations in PCNSL were identified using NGS. Mutations in multiple genes highlights the complex molecular heterogeneity of PCNSL. Enrichment analysis revealed possible pathogenesis. Further exploration of new driver genes could provide novel insights into diagnosis and precision medicine for PCNSL.


Assuntos
Genômica , Linfoma não Hodgkin , Humanos , Encéfalo , Matriz Extracelular , Instalações de Saúde
18.
Int J Biol Macromol ; 251: 126220, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37572805

RESUMO

High-toughness biodegradable poly(lactic acid) (PLA) has always been intensively pursued on the way of replacing traditional petroleum-based plastics. Regulating microstructures to achieve self-toughening holds great promise due to avoidance of incorporating other heterogeneous components. Herein, we propose a straightforward and effective way to tailor microstructures and properties of PLA through melt-stretching and quenching of slightly crosslinked samples. The melt stretching drives chains orientation and crystallization at high temperature, while the quenching followed can freeze the crystallization process to any stage. For the first time, we prepare a type of transparent and low-crystalline PLA filled with rod-like ß-form shish, which displays an outstanding tensile toughness, almost 17 times that of the conventional technique-processed one. This mechanical superiority is enabled by an integration of high ductility due to oriented chain network, and high tensile stress endowed by nanofibrous filler's role of ß-form shish. Furthermore, the mechanically toughened PLA is demonstrated to generate the richest micro-cracks and shear bands under loading, which can effectively dissipate the deformational energy and underlie the high toughness. This work opens a new prospect for the bottom-up design of high-performance bio-based PLA materials that are tough, ductile and transparent by precise microstructural regulation through scalable melt processing route.

19.
Mol Neurodegener ; 18(1): 59, 2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37649100

RESUMO

BACKGROUND: Amyloid-related imaging abnormalities (ARIA) have been identified as the most common and serious adverse events resulting from pathological changes in the cerebral vasculature during several recent anti-amyloid-ß (Aß) immunotherapy trials. However, the precise cellular and molecular mechanisms underlying how amyloid immunotherapy enhances cerebral amyloid angiopathy (CAA)-mediated alterations in vascular permeability and microhemorrhages are not currently understood. Interestingly, brain perivascular macrophages have been implicated in regulating CAA deposition and cerebrovascular function however, further investigations are required to understand how perivascular macrophages play a role in enhancing CAA-related vascular permeability and microhemorrhages associated with amyloid immunotherapy. METHODS: In this study, we examined immune responses induced by amyloid-targeting antibodies and CAA-induced microhemorrhages using histology and gene expression analyses in Alzheimer's disease (AD) mouse models and primary culture systems. RESULTS: In the present study, we demonstrate that anti-Aß (3D6) immunotherapy leads to the formation of an antibody immune complex with vascular amyloid deposits and induces the activation of CD169+ perivascular macrophages. We show that macrophages activated by antibody mediated Fc receptor signaling have increased expression of inflammatory signaling and extracellular matrix remodeling genes such as Timp1 and MMP9 in vitro and confirm these key findings in vivo. Finally, we demonstrate enhanced vascular permeability of plasma proteins and recruitment of inflammatory monocytes around vascular amyloid deposits, which are associated with hemosiderin deposits from cerebral microhemorrhages, suggesting the multidimensional roles of activated perivascular macrophages in response to Aß immunotherapy. CONCLUSIONS: In summary, our study establishes a connection between Aß antibodies engaged at CAA deposits, the activation of perivascular macrophages, and the upregulation of genes involved in vascular permeability. However, the implications of this phenomenon on the susceptibility to microhemorrhages remain to be fully elucidated. Further investigations are warranted to determine the precise role of CD169 + perivascular macrophages in enhancing CAA-mediated vascular permeability, extravasation of plasma proteins, and infiltration of immune cells associated with microhemorrhages.


Assuntos
Doença de Alzheimer , Angiopatia Amiloide Cerebral , Animais , Camundongos , Monócitos , Placa Amiloide , Peptídeos beta-Amiloides , Macrófagos , Proteínas Amiloidogênicas
20.
Math Biosci Eng ; 20(7): 13415-13433, 2023 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-37501494

RESUMO

For wearable electrocardiogram (ECG) acquisition, it was easy to infer motion artifices and other noises. In this paper, a novel end-to-end ECG denoising method was proposed, which was implemented by fusing the Efficient Channel Attention (ECA-Net) and the cycle consistent generative adversarial network (CycleGAN) method. The proposed denoising model was optimized by using the ECA-Net method to highlight the key features and introducing a new loss function to further extract the global and local ECG features. The original ECG signal came from the MIT-BIH Arrhythmia Database. Additionally, the noise signals used in this method consist of a combination of Gaussian white noise and noises sourced from the MIT-BIH Noise Stress Test Database, including EM (Electrode Motion Artifact), BW (Baseline Wander) and MA (Muscle Artifact), as well as mixed noises composed of EM+BW, EM+MA, BW+MA and EM+BW+MA. Moreover, corrupted ECG signals were generated by adding different levels of single and mixed noises to clean ECG signals. The experimental results show that the proposed method has better denoising performance and generalization ability with higher signal-to-noise ratio improvement (SNRimp), as well as lower root-mean-square error (RMSE) and percentage-root-mean-square difference (PRD).


Assuntos
Algoritmos , Processamento de Sinais Assistido por Computador , Eletrocardiografia/métodos , Teste de Esforço , Razão Sinal-Ruído
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