Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 277
Filtrar
1.
ACS Cent Sci ; 10(3): 717-728, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38559297

RESUMO

Direct inhibitor of tau aggregation has been extensively studied as potential therapeutic agents for Alzheimer's disease. However, the natively unfolded structure of tau complicates the structure-based ligand design, and the relatively large surface areas that mediate tau-tau interactions in aggregation limit the potential for identifying high-affinity ligand binding sites. Herein, a group of isatin-pyrrolidinylpyridine derivative isomers (IPP1-IPP4) were designed and synthesized. They are like different forms of molecular "transformers". These isatin isomers exhibit different inhibitory effects on tau self-aggregation or even possess a depolymerizing effect. Our results revealed for the first time that the direct inhibitor of tau protein aggregation is not only determined by the previously reported conjugated structure, substituent, hydrogen bond donor, etc. but also depends more importantly on the molecular shape. In combination with molecular docking and molecular dynamics simulations, a new inhibition mechanism was proposed: like a "molecular clip", IPP1 could noncovalently bind and fix a tau polypeptide chain at a multipoint to prevent the transition from the "natively unfolded conformation" to the "aggregation competent conformation" before nucleation. At the cellular and animal levels, the effectiveness of the inhibitor of the IPP1 has been confirmed, providing an innovative design strategy as well as a lead compound for Alzheimer's disease drug development.

2.
Nano Lett ; 24(15): 4546-4553, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38588452

RESUMO

Organic materials have attracted extensive attention for potassium-ion batteries due to their flexible structure designability and environmental friendliness. However, organic materials generally suffer from unavoidable dissolution in aprotic electrolytes, causing an unsatisfactory electrochemical performance. Herein, we designed a weakly solvating electrolyte to boost the potassium storage performance of perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA). The electrolyte induces an in situ morphology evolution and achieves a nanowire structure. The weakly dissolving capability of ethylene glycol diethyl ether-based electrolyte and unique nanowire structure effectively avoid the dissolution of PTCDA. As a result, PTCDA shows excellent cycling stability (a capacity retention of 89.1% after 2000 cycles) and good rate performance (70.3 mAh g-1 at 50C). In addition, experimental detail discloses that the sulfonyl group plays a key role in inducing morphology evolution during the charge/discharge process. This work opens up new opportunities in electrolyte design for organic electrodes and illuminates further developments of potassium-ion batteries.

3.
Opt Express ; 32(7): 10786-10800, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38570944

RESUMO

As a new type of active Earth observation technology, airborne hyperspectral lidar combines the advantages of traditional lidar 3D information acquisition and passive hyperspectral imaging technology, and it can achieve integrated imaging detection with a high spatial and hyperspectral resolution. Thus, it has become an important future direction of Earth surface remote sensing technology. This article introduces the design and development of an airborne hyperspectral imaging lidar system. The hyperspectral lidar adopts a focal plane splitting method, combined with an array of 168 optical fibers, to couple wide-spectral-range laser echo signals one by one to the corresponding single tube detector, achieving efficient splitting and precise coupling of supercontinuum laser pulse echo signals. This article proposes a fast synchronous calibration method that is suitable for hyperspectral imaging lidar systems. Results show that the spectral range of the hyperspectral lidar system is 400-900 nm, and the spectral resolution of single-fiber detection is greater than 3 nm. Notably, this article focuses on analyzing the abnormal detection channels based on the calibration results. With the test results of adjacent channels combined, the reason for the abnormal spectral bandwidth of channel 17 is analyzed as an example. This research points out the direction for verifying the design parameters of the hyperspectral lidar prototype and lays an important foundation for airborne flight test of the hyperspectral lidar.

4.
Nanomicro Lett ; 16(1): 159, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512520

RESUMO

Thermoregulatory textiles, leveraging high-emissivity structural materials, have arisen as a promising candidate for personal cooling management; however, their advancement has been hindered by the underperformed water moisture transportation capacity, which impacts on their thermophysiological comfort. Herein, we designed a wettability-gradient-induced-diode (WGID) membrane achieving by MXene-engineered electrospun technology, which could facilitate heat dissipation and moisture-wicking transportation. As a result, the obtained WGID membrane could obtain a cooling temperature of 1.5 °C in the "dry" state, and 7.1 °C in the "wet" state, which was ascribed to its high emissivity of 96.40% in the MIR range, superior thermal conductivity of 0.3349 W m-1 K-1 (based on radiation- and conduction-controlled mechanisms), and unidirectional moisture transportation property. The proposed design offers an approach for meticulously engineering electrospun membranes with enhanced heat dissipation and moisture transportation, thereby paving the way for developing more efficient and comfortable thermoregulatory textiles in a high-humidity microenvironment.

5.
World J Clin Oncol ; 15(2): 302-316, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38455139

RESUMO

BACKGROUND: Bladder cancer (BC) is the most common urological tumor. It has a high recurrence rate, displays tutor heterogeneity, and resists chemotherapy. Furthermore, the long-term survival rate of BC patients has remained unchanged for decades, which seriously affects the quality of patient survival. To improve the survival rate and prognosis of BC patients, it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention. Transmembrane 9 superfamily member 1 (TM9SF1), also known as MP70 and HMP70, is a member of a family of nine transmembrane superfamily proteins, which was first identified in 1997. TM9SF1 can be expressed in BC, but its biological function and mechanism in BC are not clear. AIM: To investigate the biological function and mechanism of TM9SF1 in BC. METHODS: Cells at 60%-80% confluence were transfected with lentiviral vectors for 48-72 h to achieve stable TM9SF1 overexpression or silencing in three BC cell lines (5637, T24, and UM-UC-3). The effect of TM9SF1 on the biological behavior of BC cells was then investigated through CCK8, wound-healing assay, transwell assay, and flow cytometry. RESULTS: Overexpression of TM9SF1 increased the in vitro proliferation, migration, and invasion of BC cells by promoting the entry of BC cells into the G2/M phase. Silencing of TM9SF1 inhibited in vitro proliferation, migration, and invasion of BC cells and blocked BC cells in the G1 phase. CONCLUSION: TM9SF1 may be an oncogene in BC.

6.
ACS Nano ; 18(13): 9365-9377, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38517349

RESUMO

The emerging field of wearable electronics requires power sources that are flexible, lightweight, high-capacity, durable, and comfortable for daily use, which enables extensive use in electronic skins, self-powered sensing, and physiological health monitoring. In this work, we developed the core-shell and biocompatible Cs2InCl5(H2O)@PVDF-HFP nanofibers (CIC@HFP NFs) by one-step electrospinning assisted self-assembly method for triboelectric nanogenerators (TENGs). By adopting lead-free Cs2InCl5(H2O) as an inducer, CIC@HFP NFs exhibited ß-phase-enhanced and self-aligned nanocrystals within the uniaxial direction. The interface interaction was further investigated by experimental measurements and molecular dynamics, which revealed that the hydrogen bonds between Cs2InCl5(H2O) and PVDF-HFP induced automatically well-aligned dipoles and stabilized the ß-phase in the CIC@HFP NFs. The TENG fabricated using CIC@HFP NFs and nylon-6,6 NFs exhibited significant improvement in output voltage (681 V), output current (53.1 µA) and peak power density (6.94 W m-2), with the highest reported output performance among TENGs based on halide-perovskites. The energy harvesting and self-powered monitoring performance were further substantiated by human motions, showcasing its ability to charge capacitors and effectively operate electronics such as commercial LEDs, stopwatches, and calculators, demonstrating its promising application in biomechanical energy harvesting and self-powered sensing.

7.
Adv Mater ; : e2401264, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38545963

RESUMO

Over the past few decades, significant progress in piezo-/triboelectric nanogenerators (PTEGs) has led to the development of cutting-edge wearable technologies. Nanofibers with good designability, controllable morphologies, large specific areas, and unique physicochemical properties provide a promising platform for PTEGs for various advanced applications. However, the further development of nanofiber-based PTEGs is limited by technical difficulties, ranging from materials design to device integration. Herein, the current developments in PTEGs based on electrospun nanofibers are systematically reviewed. This review begins with the mechanisms of PTEGs and the advantages of nanofibers and nanodevices, including high breathability, waterproofness, scalability, and thermal-moisture comfort. In terms of materials and structural design, novel electroactive nanofibers and structure assemblies based on 1D micro/nanostructures, 2D bionic structures, and 3D multilayered structures are discussed. Subsequently, nanofibrous PTEGs in applications such as energy harvesters, personalized medicine, personal protective equipment, and human-machine interactions are summarized. Nanofiber-based PTEGs still face many challenges such as energy efficiency, material durability, device stability, and device integration. Finally, the research gap between research and practical applications of PTEGs is discussed, and emerging trends are proposed, providing some ideas for the development of intelligent wearables.

8.
Int J Biol Macromol ; 265(Pt 1): 130714, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462116

RESUMO

In this study, hydrophobic sodium alginate/anthocyanin/cellulose nanocrystal indicator films were fabricated by incorporating nanosilica (NS) as a waterproofing layer. The concentrations and formation methods (spraying (S), coating (C), and impregnation (I)) of the NS layer (denoted as NSS, NSC, NSI, respectively) were optimized. The results indicated that the optimum concentration of the NS layer was 5 % at a water contact angle (WCA) 110.5°. Further, Fourier transform infrared spectra showed the presence of SiOSi and SiCH3 groups in the NSS, NSC, and NSI films, and X-ray diffraction spectra indicated that original structures of these films were disordered. Moreover, the surface morphology, mechanical properties, and light transmission were affected by the NS layer, and the optimal layer was found to be NSI. After 10 days of storage at 100 % humidity, the NSI film exhibited low water vapor adsorption (37.22 g) and permeability (0.1484 g/m·s·Pa·10-11) and a high WCA (110.2°). In addition, the NSI film exhibited a visible color shift with an increasing pH of the buffer solution. A monitoring test of fish freshness showed that the NSI film displayed a distinctive color change corresponding to fish spoilage during 14 days of storage. This indicates that NSI has high potential in indicator film applications.


Assuntos
Alginatos , Antocianinas , Animais , Adsorção , Celulose , Peixes , Sódio , Embalagem de Alimentos , Concentração de Íons de Hidrogênio
9.
Biochem Genet ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451400

RESUMO

Discoid lupus erythematosus (DLE) is a disorder of the immune system commonly seen in women of childbearing age. The pathophysiology and aetiology are still poorly understood, and no cure is presently available. Therefore, there is an urgent need to explore the underlying molecular mechanisms, as well as search for new therapeutic targets. Gene expression data from skin biopsies samples of DLE patients and healthy controls were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between DLE and healthy control samples were identified by differential expression analysis. Samples were analysed using CIBERSORT to examine the proportion of immune infiltration. Weighted gene co-expression network analysis was used to screen for the module most relevant to immune infiltration. Candidate genes were uploaded to the TRRUST database to obtain the potential transcription factors regulating these genes. Protein-protein interaction (PPI) analysis was performed to obtain the hub genes most associated with immune infiltration among the candidate genes. A total of 273 DEGs were identified between the DLE and healthy control samples. The results of immunoinfiltration analysis showed that the abundances of resting memory CD4 T cells, activated memory CD4 T cells and M1 macrophages were significantly higher, while those of resting infiltration of plasma cells, regulatory T cells and dendritic cells were lower in DLE samples than in healthy control samples. Correlation analysis showed that ISG15, TRIM22, XAF1, IFIT2, OAS2, OAS3, OAS1, IFI44, IFI6, BST2, IFIT1 and MX2 were negatively correlated with the abundances of plasma cells, T-cell regulatory cells and resting dendritic cells and positively correlated with activated memory CD4 T cells and M1 macrophages. Our study shows that these hub genes may regulate DLE via immune-related pathways mediated by the infiltration of these immune cells.

10.
Microb Cell ; 11: 29-40, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38375207

RESUMO

Intratumoral microbiota can regulate the tumor immune microenvironment (TIME) and mediate tumor prognosis by promoting inflammatory response or inhibiting anti-tumor effects. Recent studies have elucidated the potential role of local tumor microbiota in the development and progression of lung adenocarcinoma (LUAD). However, whether intratumoral microbes are involved in the TIME that mediates the prognosis of LUAD remains unknown. Here, we obtained the matched tumor microbiome and host transcriptome and survival data of 478 patients with LUAD in The Cancer Genome Atlas (TCGA). Machine learning models based on immune cell marker genes can predict 1- to 5-year survival with relative accuracy. Patients were stratified into high- and low-survival-risk groups based on immune cell marker genes, with significant differences in intratumoral microbial communities. Specifically, patients in the high-risk group had significantly higher alpha diversity (p < 0.05) and were characterized by an enrichment of lung cancer-related genera such as Streptococcus. However, network analysis highlighted a more active pattern of dominant bacteria and immune cell crosstalk in TIME in the low-risk group compared to the high-risk group. Our study demonstrated that intratumoral microbiota-immune crosstalk was strongly associated with prognosis in LUAD patients, which would provide new targets for the development of precise therapeutic strategies.

11.
ACS Appl Mater Interfaces ; 16(7): 8310-8320, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38343060

RESUMO

The COVID-19 pandemic has become an unprecedented global medical emergency, resulting in more than 5 million deaths. Acute respiratory distress syndrome (ARDS) caused by COVID-19, characterized by the release of a large number of pro-inflammatory cytokines and the production of excessive toxic ROS, is the most common serious complication leading to death. To develop new strategies for treating ARDS caused by COVID-19, a mouse model of ARDS was established by using lipopolysaccharide (LPS). Subsequently, we have constructed a novel nanospray with anti-inflammatory and antioxidant capacity by loading pentoxifylline (PTX) and edaravone (Eda) on zeolite imidazolate frameworks-8 (ZIF-8). This nanospray was endowed with synergetic therapy, which could kill two birds with one stone: (1) the loaded PTX played a powerful anti-inflammatory role by inhibiting the activation of inflammatory cells and the synthesis of pro-inflammatory cytokines; (2) Eda served as a free radical scavenger in ARDS. Furthermore, compared with the traditional intravenous administration, nanosprays can be administered directly and inhaled efficiently and reduce the risk of systemic adverse reactions greatly. This nanospray could not only coload two drugs efficiently but also realize acid-responsive release on local lung tissue. Importantly, ZIF8-EP nanospray showed an excellent therapeutic effect on ARDS in vitro and in vivo, which provided a new direction for the treatment of ARDS.


Assuntos
COVID-19 , Pentoxifilina , Síndrome do Desconforto Respiratório , Animais , Camundongos , Humanos , Pentoxifilina/farmacologia , Pentoxifilina/uso terapêutico , Edaravone/uso terapêutico , Pandemias , Pulmão , Síndrome do Desconforto Respiratório/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Citocinas , Concentração de Íons de Hidrogênio , Lipopolissacarídeos
12.
Small ; : e2309750, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38299490

RESUMO

Nanoarchitectonics of semiconductors shed light on efficient photocatalytic hydrogen evolution by precisely controlling the surface microenvironment of cocatalysts. Taking cadmium zinc sulfide (CZS) nanoparticles as a target, the spontaneous modifications are conducted by interactions between surface Cd2+ /Zn2+ atoms and thiol groups in thioglycolic acid. The capping ligand impacts the semiconductor surface with a negative electronic environment, contributing to the full coverage of CZS by nickel-cobalt hydroxides (NiCo-LDHs) cocatalysts. The obtained core-shell CZS@NiCo-LDHs, possessing a shell thickness of ≈20 nm, exhibits a distinguished topology (SBET  = 87.65m2  g-1 ), long surface carrier lifetime, and efficient charge-hole separation. Further photocatalytic hydrogen evaluation demonstrates an enhanced H2 evolution rate of 18.75 mmol g-1  h-1 with an apparent quantum efficiency of 16.3% at 420 nm. The recorded catalytic performance of the core-shell sample is 44.6 times higher than that of pure CZS nanospheres under visible light irradiation. Further density functional theory simulations indicate that sulfur atoms play the role of charge acceptor and surface Ni/Co atoms are electron donors, as well as a built-in electric field effect can be established. Altogether, this work takes advantage of strong S affinity from surface metal atoms, revealing the interfacial engineering toward improved visible-light-driven photocatalytic hydrogen evolution (PHE) activity.

13.
Nano Lett ; 24(2): 657-666, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38180824

RESUMO

The cooling power provided by radiative cooling is unwanted during cold hours. Therefore, self-adaptive regulation is desired for radiative cooling, especially in all-weather applications. However, current routes for radiative cooling regulation are constrained by substrates and complicated processing. Here, self-adaptive radiative cooling regulation on various potential substrates (transparent wood, PET, normal glass, and cement) was achieved by a Fabry-Perot structure consisting of a silver nanowires (AgNWs) bottom layer, PMMA spacer, and W-VO2 top layer. The emissivity-modulated transparent wood (EMTW) exhibits an emissivity contrast of 0.44 (ε8-13-L = ∼0.19 and ε8-13-H = ∼0.63), which thereby yields considerable energy savings across different climate zones. The emissivity contrast can be adjusted by varying the spinning parameters during the deposition process. Positive emissivity contrast was also achieved on three other industrially relevant substrates via this facile and widely applicable route. This proves the great significance of the approach to the promotion and wide adoption of radiative cooling regulation concept in the built environment.

14.
Adv Healthc Mater ; 13(7): e2302333, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38253350

RESUMO

In recent years, the anticancer effects of disulfiram, a clinical drug for anti-alcoholism, are confirmed. However, several defects limit the clinical translation of disulfiram obviously, such as Cu(II)-dependent anticancer activity, instability, and non-selectivity for cancer cells. Herein, a phosphate and hydrogen peroxide dual-responsive nanoplatform (PCu-HA-DQ) is reported, which is constructed by encapsulating disulfiram prodrug (DQ) and modifying hyaluronic acid (HA) on copper doping metal-organic frameworks (PCu MOFs). PCu-HA-DQ is expected to accumulate in tumor by targeting CD-44 receptors and enable guidance with magnetic resonance imaging. Inside the tumor, Cu(DTC)2 will be generated in situ based on a dual-responsive reaction. In detail, the high concentration of phosphate can induce the release of DQ, after that, the intracellular hydrogen peroxide will further mediate the generation of Cu(DTC)2 . In vitro and in vivo results indicate PCu-HA-DQ can induce the apoptosis as well as immunogenic cell death (ICD) of tumor cells distinctly, leading to enhanced immune checkpoint inhibitor (ICI) efficacy by combining the anti-programmed death-1 antibody. This work provides a portable strategy to construct a dual-responsive nanoplatform integrating tumor-targeted ability and multi-therapy, and the designed nanoplatform is also an ICD inducer, which presents a prospect for boosting systemic antitumor immunity and ICI efficacy.


Assuntos
Nanopartículas , Neoplasias , Pró-Fármacos , Humanos , Pró-Fármacos/uso terapêutico , Dissulfiram/uso terapêutico , Morte Celular Imunogênica , Cobre/farmacologia , Peróxido de Hidrogênio , Neoplasias/tratamento farmacológico , Imunoterapia/métodos , Fosfatos , Linhagem Celular Tumoral , Microambiente Tumoral , Nanopartículas/uso terapêutico
15.
Int J Biol Macromol ; 256(Pt 2): 128444, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38035958

RESUMO

This study developed an aqueous solution blending and freeze-drying method to prepare an antibacterial shape memory foam (WPPU/CNF) based on waterborne PHMG-polyurethane and cellulose nanofibers derived from bamboo in response to the increasing demand for environmentally friendly, energy conserving, and multifunctional foams. The obtained WPPU/CNF composite foam has a highly porous network structure with well-dispersed CNFs forming hydrogen bonds with the WPPU matrix, which results in a stable and rigid cell skeleton with enhanced mechanical properties (80 KPa) and anti-abrasion ability. The presence of guanidine in the polyurethane chain endowed the WPPU/CNF composite foam with an instinctive and sustained antibacterial ability against Escherichia coli and Staphylococcus aureus. The WPPU/CNF composite foam exhibited a water-sensitive shape memory function in a cyclic shape memory program because of the chemomechanical adaptability of the hydrogen-bonded network of CNFs in the elastomer matrix. The shape-fixation ratio for local compression reached 95 %, and the shape-recovery rate reached 100 %. This allows the WPPU/CNF pad prototype to reversibly adjust the undulation height to adapt to plantar ulcers, which can reduce the local plantar pressure by 60 %. This study provides an environmentally friendly strategy for cellulose-based composite fabrication and enriches the design and application of intelligent foam devices.


Assuntos
Celulose , Nanofibras , Celulose/farmacologia , Celulose/química , Poliuretanos/farmacologia , Antibacterianos/farmacologia , Composição de Medicamentos , Nanofibras/química , Água/química
16.
Small ; 20(1): e2304705, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37653612

RESUMO

Extreme environments can cause severe harm to human health, and even threaten life safety. Lightweight, breathable clothing with multi-protective functions would be of great application value. However, integrating multi-protective functions into nanofibers in a facile way remains a great challenge. Here, a one-step co-electrospinning-electrospray strategy is developed to fabricate a superhydrophobic multi-protective membrane (S-MPM). The water contact angle of S-MPM can reach up to 164.3°. More importantly, S-MPM can resist the skin temperature drop (11.2 °C) or increase (17.2 °C) caused by 0 °C cold or 70 °C hot compared with pure electrospun membrane. In the cold climate (-5 °C), the anti-icing time of the S-MPM is extended by 2.52 times, while the deicing time is only 1.45 s due to the great photothermal effect. In a fire disaster situation, the total heat release and peak heat release rate values of flame retarded S-MPM drop sharply by 24.2% and 69.3%, respectively. The S-MPM will serve as the last line of defense for the human body and has the potential to trigger a revolution in the practical application of next-generation functional clothing.


Assuntos
Roupa de Proteção , Temperatura Cutânea , Humanos , Temperatura Baixa , Temperatura Alta , Ambientes Extremos
17.
ACS Appl Mater Interfaces ; 16(1): 1899-1910, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38146149

RESUMO

The cosmetics industry has a worrying impact on the environment, including the plastics used in products and packaging and environmentally unfriendly additives. In this study, we present an environment-friendly triode-like facial mask (TFM) that utilizes only green and degradable raw materials, nontoxic and harmless solvents, and electric energy to achieve distinct switchable directional water transport properties, avoids a wet storage environment, and reduces excessive packaging. The TFM demonstrates droplet stability when not in contact with the skin while facilitating rapid liquid transfer (15 µL) within durations of 2.8 s (dry skin) and 1.9 s (moist skin) upon contact. We elucidate the underlying mechanism behind this triode-like behavior, emphasizing the synergistic interaction of the wettability gradient, Gibbs pinning, and additional circumferential capillary force. Moreover, the TFM exhibits a reduction in the proportion of aging cells, decreasing from 44.33 to 13.75%, while simultaneously providing antibacterial and skin-beautifying effects. The TFM brings a novel experience while also holding the potential to reduce environmental pollution in the production, packaging, use, and recycling of cosmetics products.


Assuntos
Cosméticos , Máscaras , Pele , Molhabilidade , Reciclagem
18.
ACS Appl Mater Interfaces ; 15(46): 53318-53332, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37943829

RESUMO

Despite immunotherapy having revolutionized cancer therapy, the efficacy of immunotherapy in triple-negative breast cancer (TNBC) is seriously restricted due to the insufficient infiltration of mature dendritic cells (DCs) and the highly diffusion of immunosuppressive cells in the tumor microenvironment. Herein, an immunomodulatory nanoplatform (HA/Lipo@MTO@IMQ), in which the DCs could be maximally activated, was engineered to remarkably eradicate the tumor via the combination of suppressive tumor immune microenvironment reversal immunotherapy, chemotherapy, and photothermal therapy. It was noticed that the immunotherapy efficacy could be significantly facilitated by this triple-assistance therapy: First, a robust immunogenic cell death (ICD) effect was induced by mitoxantrone hydrochloride (MTO) to boost DCs maturation and cytotoxic T lymphocytes infiltration. Second, the powerful promaturation property of the toll-like receptor 7/8 (TLR7/8) agonist on DCs simultaneously strengthened the ICD effect and restricted antitumor immunity to the tumor bed and lymph nodes. On this basis, tumor-associated macrophages were also dramatically repolarized toward the antitumor M1 phenotype in response to TLR7/8 agonist to intensify the phagocytosis and reverse the immunosuppressive microenvironment. Furthermore, the recruitment of immunocompetent cells and tumor growth inhibition were further promoted by the photothermal characteristic. The nanoplatform with no conspicuous untoward effects exhibited a splendid ability to activate the systemic immune system so as to increase the immunogenicity of the tumor microenvironment, thus enhancing the tumor killing effect. Taken together, HA/Lipo@MTO@IMQ might highlight an efficient combination of therapeutic modality for TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Terapia Fototérmica , Receptor 7 Toll-Like , Microambiente Tumoral , Fatores Imunológicos , Adjuvantes Imunológicos , Imunossupressores , Imunoterapia , Linhagem Celular Tumoral
19.
Sci Bull (Beijing) ; 68(22): 2806-2816, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-37919157

RESUMO

It is difficult to infer causality from high-dimension metagenomic data due to interference from numerous confounders. By imitating the twin studies in genetic research, we develop a straightforward method-virtual twins (VTwins)-to eliminate the confounder effects by transforming the original cohort into a paired cohort of "Twin" samples with distinct phenotypes but matched taxonomic profiles. The results show that VTwins outperforms the conventional approach in the sensitivity of identifying causative features and only requires a 10-fold reduced sample size for recalling disease-associated microbes or pathways, as tested by simulated and empirical data. Benchmark test with other 16 kinds of software further validates the power and applicability of VTwins for handling high-dimension compositional datasets and mining causalities in metagenomic research. In conclusion, VTwins is straightforward and effective in handling high-diversity, high-dimension compositional data, promising applications in mining causalities for metagenomic and potentially other omics data. VTwins is open access and available at https://github.com/mengqingren/VTwins.


Assuntos
Algoritmos , Metagenoma , Humanos , Metagenoma/genética , Software , Metagenômica/métodos
20.
Biomark Res ; 11(1): 87, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794517

RESUMO

BACKGROUND AND AIM: The presence of microvascular invasion (MVI) will impair the surgical outcome of hepatocellular carcinoma (HCC). Adipose and muscle tissues have been confirmed to be associated with the prognosis of HCC. We aimed to develop and validate a nomogram based on adipose and muscle related-variables for preoperative prediction of MVI in HCC. METHODS: One hundred fifty-eight HCC patients from institution A (training cohort) and 53 HCC patients from institution B (validation cohort) were included, all of whom underwent preoperative CT scan and curative resection with confirmed pathological diagnoses. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied to data dimensionality reduction and screening. Nomogram was constructed based on the independent variables, and evaluated by external validation, calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA). RESULTS: Histopathologically identified MVI was found in 101 of 211 patients (47.9%). The preoperative imaging and clinical variables associated with MVI were visceral adipose tissue (VAT) density, intramuscular adipose tissue index (IMATI), skeletal muscle (SM) area, age, tumor size and cirrhosis. Incorporating these 6 factors, the nomogram achieved good concordance index of 0.79 (95%CI: 0.72-0.86) and 0.75 (95%CI: 0.62-0.89) in training and validation cohorts, respectively. In addition, calibration curve exhibited good consistency between predicted and actual MVI probabilities. ROC curve and DCA of the nomogram showed superior performance than that of models only depended on clinical or imaging variables. Based on the nomogram score, patients were divided into high (> 273.8) and low (< = 273.8) risk of MVI presence groups. For patients with high MVI risk, wide-margin resection or anatomical resection could significantly improve the 2-year recurrence free survival. CONCLUSION: By combining 6 preoperative independently predictive factors of MVI, a nomogram was constructed. This model provides an optimal preoperative estimation of MVI risk in HCC patients, and may help to stratify high-risk individuals and optimize clinical decision making.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...