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1.
BMJ Open ; 14(10): e081226, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39357982

RESUMO

INTRODUCTION: The presence of food product indicators may facilitate consumers in making informed healthy choices. However, it may also mislead consumers. This study aims to determine the prevalence of food products carrying food product indicators; the compliance of products bearing Malaysia's Healthier Choice Logo (HCL) and nutrition and health claims (NHC) towards the local regulations; and the credibility of the aforementioned products as healthy food products based on the international regulation in the Malaysian market. METHOD: This is a cross-sectional market survey conducted from February to May 2023 on 3428 products sold in Malaysian supermarkets. Product information including the brand, name, nutrition information panel, food product indicator (front-of-pack nutrition labelling, NHC, other claims), ingredients list and manufacturer or importer were collected. Compliance of products carrying NHC and HCL is evaluated against local guidelines. Credibility as a healthy product is evaluated against the WHO Nutrient Profile Model for the Western Pacific Region on a subsample (products with HCL and/or NHC). RESULTS: 53% of food products surveyed had food product indicators (n=1809). A total of 32% carried at least one NHC (n=1101), of which 47% had excellent overall compliance (n=522). Only 4% carried Malaysia's HCL (n=138), of which 48% had excellent nutrient compliance (n=66). Only 13% of the products carrying Malaysia's HCL and NHC could be identified as absolute healthy food products as defined by the WHO standard (n=147). CONCLUSION: Although half of the products surveyed had food product indicators, merely half of them had excellent compliance towards the standards. Only 13% of the subsample qualified as healthy food products. Voluntary application of the local HCL was low among food industries. Ensuring high standards of compliance and credibility of food products in the Malaysian market is crucial for food companies and government authorities.


Assuntos
Rotulagem de Alimentos , Malásia , Estudos Transversais , Humanos , Rotulagem de Alimentos/normas , Supermercados , Valor Nutritivo , Dieta Saudável/normas , Dieta Saudável/estatística & dados numéricos , Comportamento do Consumidor/estatística & dados numéricos , Inquéritos e Questionários
2.
Adv Mater ; : e2409914, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39380383

RESUMO

The generation of non-exhausted effector T-cells depends on vaccine's spatiotemporal profile, and untimely delivery and low targeting to lymph node (LN) paracortex by standard bolus immunization show limited efficacy. By recapitulating the dynamic processes of acute infection, a bioadhesive immune niche domain (BIND) is developed that facilitates the delivery of timely-activating conjugated nanovaccine (t-CNV) in a metronomic-like manner and increased the accumulation and retention of TANNylated t-CNV (tannic acid coated t-CNV) in LN by specifically binding to collagen in subcapsular sinus where they gradually transformed into TANNylated antigen-adjuvant conjugate by proteolysis, inducing their penetration into paracortex through the collagen-binding in LN conduit and evoking durable antigen-specific CD8+ T-cell responses. The BIND combined with t-CNV, mRNA vaccine, IL-2, and anti-PD-1 antibody also significantly enhanced cancer immunotherapy by the dynamic modulation of immunological landscape of tumor microenvironment. The results provide material design strategy for dynamic immunomodulation that can potentiate non-exhausted T-cell-based immunotherapy.

3.
J Trauma Inj ; 37(1): 37-47, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39381151

RESUMO

Purpose: This study aimed at developing a novel tube thoracostomy technique using the sternum, a fixed anatomical structure, as an indicator to reduce the possibility of incorrect chest tube positioning and complications in patients with chest trauma. Methods: This retrospective study analyzed the data of 184 patients with chest trauma who were aged ≥18 years, visited a single regional trauma center in Korea between April and June 2022, and underwent chest computed tomography (CT) with their arms down. The conventional gold standard, 5th intercostal space (ICS) method, was compared to the lower 1/2, 1/3, and 1/4 of the sternum method by analyzing CT images. Results: When virtual tube thoracostomy routes were drawn at the mid-axillary line at the 5th ICS level, 150 patients (81.5%) on the right side and 179 patients (97.3%) on the left did not pass the diaphragm. However, at the lower 1/2 of the sternum level, 171 patients (92.9%, P<0.001) on the right and 182 patients (98.9%, P= 0.250) on the left did not pass the diaphragm. At the 5th ICS level, 129 patients (70.1%) on the right and 156 patients (84.8%) on the left were located in the safety zone and did not pass the diaphragm. Alternatively, at the lower 1/2, 1/3, and 1/4 of the sternum level, 139 (75.5%, P=0.185), 49 (26.6%, P<0.001), and 10 (5.4%, P<0.001), respectively, on the right, and 146 (79.3%, P=0.041), 69 (37.5%, P<0.001), and 16 (8.7%, P<0.001) on the left were located in the safety zone and did not pass the diaphragm. Compared to the conventional 5th ICS method, the sternum 1/2 method had a safety zone prediction sensitivity of 90.0% to 90.7%, and 97.3% to 100% sensitivity for not passing the diaphragm. Conclusions: Using the sternum length as a tube thoracostomy indicator might be feasible.

4.
ACS Appl Bio Mater ; 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39392900

RESUMO

Cell-based immunotherapies have emerged as promising cancer treatment modalities, demonstrating remarkable clinical efficacy. As interest in applying immune cell-based therapies to solid tumors has gained momentum, experimental models that enable long-term monitoring and mimic clinical administration are increasingly necessary. This study explores the potential of scaffold-based cell culture technologies, specifically three-dimensional (3D) extracellular matrix (ECM)-like frameworks, as promising solutions. These frameworks facilitate unhindered immune cell growth and enable continuous cancer cell culture. The three-dimensional (3D) cell culture model was developed using tailored scaffolds for natural killer (NK) cell culture. Within this framework, A549 lung cancer cells were cocultured with NK cells, allowing real-time monitoring for up to 28 days. The expression of critical markers associated with anticancer drug resistance and epithelial-mesenchymal transition (EMT) was evaluated in cancer cells within this 3D culture context. Compared to conventional 2D monolayer cultures, this 3D scaffold-based culture revealed that solid tumor cells, specifically A549 cells, exhibited heightened resistance to anticancer drugs. Additionally, the 3D culture environment upregulated the expression of EMT markers namely vimentin, N-cadherin, and fibronectin, while NK and zEGFR-CAR-NK cells displayed anticancer effects. In the two-dimensional (2D) coculture, only zEGFR-CAR-NK cells exhibited such effects in the 3D coculture system, highlighting an intriguing inconsistency with the 2D culture model, further confirmed by in vivo experiments. This in vitro 3D cell culture model reliably predicts outcomes in NK immunotherapy experiments. Thus, it represents a valuable tool for investigating drug resistance mechanisms and assessing the efficacy of immune cell-based therapies. By bridging the gap between in vitro and in vivo investigations, this model effectively translates potential treatments into animal models and facilitates rigorous preclinical evaluations.

5.
Discov Nano ; 19(1): 145, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256285

RESUMO

Breast cancer is one of the leading causes of death among women globally, making its diagnosis and treatment challenging. The use of nanotechnology for cancer diagnosis and treatment is an emerging area of research. To address this issue, multiwalled carbon nanotubes (MWCNTs) were ligand exchanged with butyric acid (BA) to gain hydrophilic character. The successful functionalization was confirmed by FTIR spectroscopy. Surface morphology changes were observed using SEM, while TEM confirmed the structural integrity of the MWCNTs after functionalization. Particle size, zeta potential, and UV spectroscopy were also performed to further characterize the nanoparticles. The breast cancer aptamer specific to Mucin-1 (MUC-1) was then conjugated with the functionalized MWCNTs. These MWCNTs successfully targeted breast cancer cells (MDA-MB-231) as examined by cellular uptake studies and exhibited a reduction in cancer-induced inflammation, as evidenced by gene transcription (qPCR) and protein expression (immunoblotting) levels. Immunoblot and confocal-based immunofluorescence assay (IFA) indicated the ability of CNTs to induce photothermal cell death of MDA-MB-231 cells. Upon imaging, cancer cells were effectively visualized due to the MWCNTs' ability to act as magnetic resonance imaging (MRI) contrast agents. Additionally, MWCNTs demonstrated photothermal capabilities to eliminate bound cancer cells. Collectively, our findings pave the way for developing aptamer-labeled MWCNTs as viable "theranostic alternatives" for breast cancer treatment.

6.
Aging Med (Milton) ; 7(4): 528-534, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39234199

RESUMO

Dementia is characterized by a progressive decline in cognition, behavioral and psychological symptoms (BPSD), and quality of life (QoL). The lack of curative therapies has led to a psychosocial discourse prioritizing QoL of people thriving with dementia (PTD). Group reminiscence therapy (RT) is a relatively inexpensive intervention, with music prompts being a preferred choice, owing to robust musical memory in the early disease stage. However, a synthesis of current evidence is needed to inform research and clinical use of group music RT in dementia care. Therefore, we conducted a systematic review on PubMed, Scopus, CINAHL, APA PsycInfo, and APA PsycArticles to critically appraise published randomized controlled trials examining group music RT to improve cognition, BPSD, and QoL in PTD. Of 14,725 articles, two RCTs involving 102 PTD were included. All studies used prerecorded music for group music RT. All studies were deemed of good quality, adhering to intention-to-treat analysis and assessor blinding. Based on the American Academy of Neurology guidelines, we assigned a Level C recommendation for group music RT for cognition and Level B recommendations for BPSD and QoL (ineffective). In conclusion, group music RT may be useful for symptomatic management in PTD. However, heterogeneous study designs, disease severity, dementia subtype, and outcome measures are likely barriers to meaningful clinical translation. Therefore, the rating of recommendations only serves as a point of reference. Future avenues include live performances as prompts for group music RT.

7.
Bioact Mater ; 42: 345-365, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39290338

RESUMO

Recently, nanovaccine-based immunotherapy has been robustly investigated due to its potential in governing the immune response and generating long-term protective immunity. However, the presentation of a tumor peptide-major histocompatibility complex to T lymphocytes is still a challenge that needs to be addressed for eliciting potent antitumor immunity. Type 1 conventional dendritic cell (cDC1) subset is of particular interest due to its pivotal contribution in the cross-presentation of exogenous antigens to CD8+ T cells. Here, the DC-derived nanovaccine (denoted as Si9GM) selectively targets cDC1s with marginal loss of premature antigen release for effective stimulator of interferon genes (STING)-mediated antigen cross-presentation. Bone marrow dendritic cell (BMDC)-derived membranes, conjugated to cDC1-specific antibody (αCLEC9A) and binding to tumor peptide (OVA257-264), are coated onto dendrimer-like polyethylenimine (PEI)-grafted silica nanoparticles. Distinct molecular weight-cargos (αCLEC9A-OVA257-264 conjugates and 2'3'-cGAMP STING agonists) are loaded in hierarchical center-radial pores that enables lysosome escape for potent antigen-cross presentation and activates interferon type I, respectively. Impressively, Si9GM vaccination leads to the upregulation of cytotoxic T cells, a reduction in tumor regulatory T cells (Tregs), M1/M2 macrophage polarization, and immune response that synergizes with αPD-1 immune checkpoint blockade. This nanovaccine fulfills a dual role for both direct T cell activation as an artificial antigen-presenting cell and DC subset maturation, indicating its utility in clinical therapy and precision medicine.

8.
Sci Rep ; 14(1): 18200, 2024 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107336

RESUMO

We evaluated the diagnostic performance of newly developed microfluidic microplate-based fluorescent ELISA for anti-SARS-CoV-2 antibody detection: the Veri-Q opti COVID-19 IgG and IgM ELISAs (hereafter, "Opti IgG/M"; MiCo BioMed, Gyeonggi-do, Republic of Korea), in comparison with conventional ELISAs. A total of 270 serum samples were analyzed, among which 90 samples were serially obtained from 25 COVID-19 patients. Another 180 samples were collected from 180 SARS-CoV-2-negative individuals. As comparative assays, we used SCoV-2 Detect IgG/M ELISA (hereafter, "InBios IgG/M"; InBios, Seattle, WA, USA) and Veri-Q COVID-19 IgG/IgM ELISA (hereafter, "Veri-Q IgG/M"; MiCo BioMed). Compared with conventional ELISAs, the Opti IgG yielded 97.1-100.0% positive percent agreement, 95.2-98.0% negative percent agreement, 96.3-97.8% total percent agreement, and kappa values of 0.90-0.94. Between the Opti IgM and the InBios IgM, the values were 93.7%, 96.6%, 95.9%, and 0.89, respectively. For the Opti IgG, sensitivities for the samples collected from 0-7, 8-14, 15-21, and ≥ 22 days after symptom onset were 40.0, 58.3, 94.1, and 100.0%, respectively. The values for the Opti IgM were 30.0, 54.2, 88.2, and 80%, respectively. The diagnostic specificities of the Opti IgG and IgM were 99.4 and 97.2%, respectively. The microfluidic microplate-based fluorescent ELISAs showed comparable diagnostic performance to conventional ELISAs for detecting anti-SARS-CoV-2 antibodies. With the combination of high throughput, a simplified workflow, and the ability to analyze reduced volumes, this new technology has great potential for improving SARS-CoV-2 serologic testing.


Assuntos
Anticorpos Antivirais , Teste Sorológico para COVID-19 , COVID-19 , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Imunoglobulina M , SARS-CoV-2 , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Imunoglobulina G/sangue , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/diagnóstico , COVID-19/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Teste Sorológico para COVID-19/métodos , Sensibilidade e Especificidade , Microfluídica/métodos , Microfluídica/instrumentação , Pessoa de Meia-Idade , Feminino , Masculino , Idoso
9.
RSC Adv ; 14(35): 25190-25197, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39139226

RESUMO

Replica molding (REM) is a powerful technique for fabricating anisotropic microparticles. Current REM methods rely on the use of gas-permeable molds for defect-free castings and facile particle recovery. However, they often encounter limitations on either technical accessibility or producible particle diversity. While the use of gas-impermeable molds presents a promising solution to these challenges, particle production within such molds necessitates addressing two critical issues: precursor loading and particle recovery. This study introduces a REM methodology specifically tailored to enable the production of anisotropic microparticles within gas-impermeable molds. To address the issue of precursor loading, our approach incorporates the air-through-precursor suction method, employing a degassed polydimethylsiloxane block to effectively eliminate air bubbles trapped in microwells. Additionally, fluorosilane pretreatment of the mold surface, along with the polyvinyl alcohol film formation, significantly enhances particle recovery up to 249-fold while ensuring particle homogeneity. This methodology demonstrates high adaptability to various gas-impermeable molds and curing techniques. The practical feasibility is illustrated through the successful production of functional composite microparticles that can be effectively utilized for oxygen sensing and self-assembly, challenging in conventional REM.

10.
Medicine (Baltimore) ; 103(35): e38483, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39213207

RESUMO

Optimal timing of revascularization for patients who presented with non-ST segment elevation myocardial infarction (NSTEMI) and severe left ventricular (LV) dysfunction is unclear. A total of 386 NSTEMI patients with severe LV dysfunction from the nationwide, multicenter, and prospective Korea Acute Myocardial Infarction Registry V (KAMIR-V) were enrolled. Severe LV dysfunction was defined as LV ejection fraction ≤ 35%. Patients with cardiogenic shock were excluded. Patients were stratified into two groups: PCI within 24 hours (early invasive group) and PCI over 24 hours (selective invasive group). Primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) including all-cause death, non-fatal MI, repeat revascularization, and stroke at 12 months after index procedure. Early invasive group showed higher incidence of in-hospital death (9.4% vs 3.3%, P = .036) and cardiogenic shock (11.5% vs 4.6%, P = .030) after PCI. Early invasive group also showed higher maximum troponin I level during admission (27.7 ±â€…44.8 ng/mL vs 14.9 ±â€…24.6 ng/mL, P = .001), compared with the selective invasive group. Early invasive group had an increased risk of 12-month MACCE, compared with selective invasive group (25.6% vs 17.1%; adjusted HR = 2.10, 95% CI 1.17-3.77, P = .006). Among NSTEMI patients with severe LV dysfunction, the early invasive strategy did not improve the clinical outcomes. This data supports that an individualized approach may benefit high-risk NSTEMI patients rather than a routine invasive approach.


Assuntos
Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Sistema de Registros , Disfunção Ventricular Esquerda , Humanos , Disfunção Ventricular Esquerda/fisiopatologia , Masculino , Feminino , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Pessoa de Meia-Idade , Idoso , Intervenção Coronária Percutânea/métodos , República da Coreia/epidemiologia , Estudos Prospectivos , Tempo para o Tratamento/estatística & dados numéricos , Mortalidade Hospitalar , Revascularização Miocárdica/métodos , Fatores de Tempo , Choque Cardiogênico/mortalidade , Choque Cardiogênico/etiologia
11.
PNAS Nexus ; 3(6): pgae213, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38881843

RESUMO

Intrinsic impediments, namely weak mechanical strength, low ionic conductivity, low electrochemical performance, and stability have largely inhibited beyond practical applications of hydrogels in electronic devices and remains as a significant challenge in the scientific world. Here, we report a biospecies-derived genomic DNA hybrid gel electrolyte with many synergistic effects, including robust mechanical properties (mechanical strength and elongation of 6.98 MPa and 997.42%, respectively) and ion migration channels, which consequently demonstrated high ionic conductivity (73.27 mS/cm) and superior electrochemical stability (1.64 V). Notably, when applied to a supercapacitor the hybrid gel-based devices exhibit a specific capacitance of 425 F/g. Furthermore, it maintained rapid charging/discharging with a capacitance retention rate of 93.8% after ∼200,000 cycles while exhibiting a maximum energy density of 35.07 Wh/kg and a maximum power density of 193.9 kW/kg. This represents the best value among the current supercapacitors and can be immediately applied to minicars, solar cells, and LED lightning. The widespread use of DNA gel electrolytes will revolutionize human efforts to industrialize high-performance green energy.

12.
JAMA Netw Open ; 7(6): e2415102, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38842810

RESUMO

Importance: Moyamoya disease (MMD) is a rare chronic cerebrovascular disease, and the outcomes of bypass management in adult patients remain controversial. Objective: To categorize adult MMD based on asymptomatic, ischemic, and hemorrhagic onset and compare the outcomes (death, hemorrhagic stroke [HS], and ischemic stroke [IS]) of bypass surgery (direct or indirect) with those of conservative management. Design, Setting, and Participants: This retrospective, nationwide, population-based longitudinal cohort study used Korean National Health Insurance Research data to identify adults (aged ≥15 years) with MMD who were diagnosed between January 1, 2008, and December 31, 2020, and followed up until December 31, 2021 (median follow-up, 5.74 [IQR, 2.95-9.42] years). A total of 19 700 participants (3194 with hemorrhagic, 517 with ischemic, and 15 989 with asymptomatic MMD) were included. Data were analyzed from January 2 to April 1, 2023. Exposures: Bypass surgery and conservative management. Main Outcomes and Measures: Death constituted the primary outcome; secondary outcomes consisted of HS or IS. Kaplan-Meier survival curve and Cox proportional hazards regression analysis were applied. The propensity score-matching and stratified analyses were performed to control covariate effects. Results: A total of 19 700 patients (mean [SD] age, 45.43 [14.98] years; 12 766 [64.8%] female) were included. Compared with conservative management, bypass was associated with a reduced risk of death (adjusted hazard ratio [AHR], 0.50 [95% CI, 0.41-0.61]; P < .001) and HS (AHR, 0.36 [0.30-0.40]; P < .001) in hemorrhagic MMD; reduced risk of IS (AHR, 0.55 [95% CI, 0.37-0.81]; P = .002) in ischemic MMD; and reduced risk of death (AHR, 0.74 [95% CI, 0.66-0.84]; P < .001) in asymptomatic MMD. However, bypass was associated with an increased risk of HS (AHR, 1.76 [95% CI, 1.56-2.00]; P < .001) in asymptomatic MMD. Both direct and indirect bypass demonstrated similar effects in hemorrhagic and asymptomatic MMD, except only direct bypass was associated with a reduced risk of IS (AHR, 0.52 [95% CI, 0.33- 0.83]; P = .01) in ischemic MMD. After stratification, bypass was associated with a reduced risk of death in patients younger than 55 years with ischemic (AHR, 0.34 [95% CI, 0.13- 0.88]; P = .03) and asymptomatic (AHR, 0.69 [95% CI, 0.60-0.79]; P < .001) MMD, but an increased risk of HS in patients 55 years or older with ischemic MMD (AHR, 2.13 [95% CI, 1.1-4.16]; P = .03). Conclusions and Relevance: The findings of this cohort study of bypass outcomes for patients with MMD emphasize the importance of tailoring management strategies in adult patients based on onset types.


Assuntos
Revascularização Cerebral , Doença de Moyamoya , Humanos , Doença de Moyamoya/cirurgia , Doença de Moyamoya/mortalidade , Doença de Moyamoya/complicações , Feminino , Masculino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Revascularização Cerebral/métodos , Estudos Longitudinais , Resultado do Tratamento , AVC Isquêmico/cirurgia , AVC Isquêmico/mortalidade , AVC Isquêmico/epidemiologia , Tratamento Conservador/estatística & dados numéricos , Tratamento Conservador/métodos , Adulto Jovem
13.
Chempluschem ; : e202400114, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38797707

RESUMO

Self-assembly of designed molecules has enabled the construction of a variety of functional nanostructures. Specifically, adaptable self-assembly has demonstrated several advantageous features for smart materials. Here, we demonstrate that an α-helical coiled coil conjugated with a dendrimer can adapt to spatial restriction due to the strong steric repulsion between dendrimer chains. The adaptable transformation of a tetrameric coiled coil to a trimeric coiled coil can be confirmed using analytical ultracentrifugation upon conjugation of the dendrimer to the coiled coil-forming building block. Interestingly, circular dichroism spectroscopy analysis of the dendrimer conjugate revealed an unconventional trend: the multimerization of the coiled coil is inversely dependent on concentration. This result implies that the spatial crowding between the bulky dendritic chains is significantly stronger than that between linear chains, thereby affecting the overall assembly process. We further illustrated the application potential by decorating the surface of gold nanorods (AuNRs) with the adaptable coiled coil. The dendrimer-coiled coil peptide conjugate can be utilized to fabricate organic-inorganic nanohybrids with enhanced colloidal and thermal stabilities. This study demonstrates that the coiled coil can engage in the adaptable mode of self-assembly with the potential to form dynamic peptide-based materials.

14.
Adv Healthc Mater ; : e2401270, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38801164

RESUMO

Current immune checkpoint blockade therapy (ICBT) predominantly targets T cells to harness the antitumor effects of adaptive immune system. However, the effectiveness of ICBT is reduced by immunosuppressive innate myeloid cells in tumor microenvironments (TMEs). Toll-like receptor 7/8 agonists (TLR7/8a) are often used to address this problem because they can reprogram myeloid-derived suppressor cells (MDSCs) and tumor-associated M2 macrophages, and boost dendritic cell (DC)-based T-cell generation; however, the systemic toxicity of TLR7/8a limits its clinical translation. Here, to address this limitation and utilize the effectiveness of TLR7/8a, this work suggests a programmed two-step activation strategy via Antibody-Trojan Immune Converter Conjugates (ATICC) that specifically targets myeloid cells by anti-SIRPα followed by reactivation of transiently inactivated Trojan TLR7/8a after antibody-mediated endocytosis. ATICC blocks the CD47-SIRPα ("don't eat me" signal), enhances phagocytosis, reprograms M2 macrophages and MDSCs, and increases cross-presentation by DCs, resulting in antigen-specific CD8+ T-cell generation in tumor-draining lymph nodes and TME while minimizing systemic toxicity. The local or systemic administration of ATICC improves ICBT responsiveness through reprogramming of the immunosuppressive TME, increased infiltration of antigen-specific CD8+ T cells, and antibody-dependent cellular phagocytosis. These results highlight the programmed and target immunomodulation via ATICC could enhance cancer immunotherapy with minimized systemic toxicities.

15.
Stroke Vasc Neurol ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38821555

RESUMO

BACKGROUND: Transdural collaterals, originating mainly from the extracalvarial superficial temporal artery and intracalvarial middle meningeal artery via the external carotid artery (ECA), have been observed after revascularisation surgery. However, the origin of these collaterals in patients with stroke with perfusion insufficiency is not yet known. Therefore, we studied the revascularisation patterns and characteristics based on the origin of these collaterals. METHODS: We employed erythropoietin pretreatment and performed multiple burr holes under local anaesthesia to achieve transdural revascularisation in patients with acute stroke with perfusion insufficiency. After 6 months, we reassessed the transfemoral cerebral angiography to evaluate the revascularisation patterns. The collaterals were categorised into intracalvarial ECA-dominant (originating from the middle meningeal artery), extracalvarial ECA-dominant (originating from the superficial temporal or occipital artery) and balanced groups. We compared various imaging parameters among these groups. RESULTS: Overall, 87 patients with 103 treated hemispheres were involved. Among them, 57.3% were classified as intracalvarial ECA-dominant, 20.4% as extracalvarial ECA-dominant and 22.3% as balanced. Most of the hemispheres with intracalvarial or extracalvarial collaterals (vs balanced collaterals) showed successful revascularisation (78/80 (97.5%) vs 12/23 (52.1%)), p<0.001). In ultrasonographic haemodynamic changes according to revascularisation pattern, only the intracalvarial ECA-dominant revascularisation was significantly associated with specific changes in ECA blood flow, leading to the conversion to a low-resistance ECA Doppler sonography waveform. CONCLUSIONS: Our findings suggest that intracalvarial ECA-dominant revascularisation plays a crucial role in the formation of transdural collaterals following combined therapy. These distinct changes in ECA haemodynamics can be non-invasively identified through bedside ultrasound studies.

16.
Int J Mol Sci ; 25(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38732183

RESUMO

The impact of microplastics (MPs) on the metabolic functions of the liver is currently unclear and not completely understood. To investigate the effects of the administration of MPs on the hepatic metabolism of normal and obese mice, alterations in the lipid, glucose (Glu), and amino acid regulation pathways were analyzed in the liver and adipose tissues of C57BL/6Korl (wild type, WT) or C57BL/6-Lepem1hwl/Korl mice (leptin knockout, Lep KO) orally administered polystyrene (PS) MPs for 9 weeks. Significant alterations in the lipid accumulation, adipogenesis, lipogenesis, and lipolysis pathways were detected in the liver tissue of MP-treated WT and Lep KO mice compared to the vehicle-treated group. These alterations in their liver tissues were accompanied by an upregulation of the serum lipid profile, as well as alterations in the adipogenesis, lipogenesis, and lipolysis pathways in the adipose tissues of MP-treated WT and Lep KO mice. Specifically, the level of leptin was increased in the adipose tissues of MP-treated WT mice without any change in their food intake. Also, MP-induced disruptions in the glycogenolysis, Glu transporter type 4 (GLUT4)-5' AMP-activated protein kinase (AMPK) signaling pathway, levels of lipid intermediates, and the insulin resistance of the liver tissues of WT and Lep KO mice were observed. Furthermore, the levels of seven endogenous metabolites were remarkably changed in the serum of WT and Lep KO mice after MP administrations. Finally, the impact of the MP administration observed in both types of mice was further verified in differentiated 3T3-L1 adipocytes and HepG2 cells. Thus, these results suggest that the oral administration of MPs for 9 weeks may be associated with the disruption of lipid, Glu, and amino acid metabolism in the liver tissue of obese WT and Lep KO mice.


Assuntos
Aminoácidos , Glucose , Metabolismo dos Lipídeos , Fígado , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microplásticos , Poliestirenos , Animais , Fígado/metabolismo , Fígado/efeitos dos fármacos , Camundongos , Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Aminoácidos/metabolismo , Administração Oral , Leptina/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Masculino , Lipogênese/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/etiologia , Obesidade/genética , Humanos , Lipólise/efeitos dos fármacos
17.
Anal Chem ; 96(18): 7204-7211, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38662417

RESUMO

The simultaneous quantification of multiple proteins is crucial for accurate medical diagnostics. A promising technology, the multiplex colorimetric immunoassay using encoded hydrogel microparticles, has garnered attention, due to its simplicity and multiplex capabilities. However, it encounters challenges related to its dynamic range, as it relies solely on the colorimetric signal analysis of encoded hydrogel microparticles at the specific time point (i.e., end-point analysis). This necessitates the precise determination of the optimal time point for the termination of the colorimetric reaction. In this study, we introduce real-time signal analysis to quantify proteins by observing the continuous colorimetric signal change within the encoded hydrogel microparticles. Real-time signal analysis measures the "slope", the rate of the colorimetric signal generation, by focusing on the kinetics of the accumulation of colorimetric products instead of the colorimetric signal that appears at the end point. By developing a deep learning-based automatic analysis program that automatically reads the code of the graphically encoded hydrogel microparticles and obtains the slope by continuously tracking the colorimetric signal, we achieved high accuracy and high throughput analysis. This technology has secured a dynamic range more than twice as wide as that of the conventional end-point signal analysis, simultaneously achieving a sensitivity that is 4-10 times higher. Finally, as a demonstration of application, we performed multiplex colorimetric immunoassays using real-time signal analysis covering a wide concentration range of protein targets associated with pre-eclampsia.


Assuntos
Colorimetria , Hidrogéis , Colorimetria/métodos , Imunoensaio/métodos , Hidrogéis/química , Humanos , Feminino , Gravidez , Pré-Eclâmpsia/diagnóstico , Aprendizado Profundo
19.
ACS Appl Mater Interfaces ; 16(9): 11787-11799, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38394678

RESUMO

The fields of plasmonics and photonic crystals (PCs) have been combined to generate model light-confining Tamm plasmon (TMM) cavities. This approach effectively overcomes the intrinsic limit of diffraction faced by dielectric cavities and mitigates losses associated with the inherent properties of plasmonic materials. In this study, nanoporous anodic alumina PCs, produced by two-step sinusoidal pulse anodization, are used as a model dielectric platform to establish the methodology for tailoring light confinement through TMM resonances. These model dielectric mirrors feature highly organized nanopores and narrow bandwidth photonic stopbands (PSBs) across different positions of the spectrum. Different types of metallic films (gold, silver, and aluminum) were coated on the top of these model dielectric mirrors. By structuring the features of the plasmonic and photonic components of these hybrid structures, the characteristics of TMM resonances were studied to elucidate effective approaches to optimize the light-confining capability of this hybrid TMM model system. Our findings indicate that the coupling of photonic and plasmonic modes is maximized when the PSB of the model dielectric mirror is broad and located within the midvisible region. It was also found that thicker metal films enhance the quality of the confined light. Gas sensing experiments were performed on optimized TMM systems, and their sensitivity was assessed in real time to demonstrate their applicability. Ag films provide superior performance in achieving the highest sensitivity (S = 0.038 ± 0.001 nm ppm-1) based on specific binding interactions between thiol-containing molecules and metal films.

20.
Genes Genomics ; 46(2): 253-261, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38236352

RESUMO

BACKGROUND: Interactions of plants with biotic stress factors including bacteria, fungi, and viruses have been extensively investigated to date. Plasmodiophora brassicae, a protist pathogen, causes clubroot disease in Cruciferae plants. Infection of Chinese cabbage (Brassica rapa) plants with P. brassica results in the formation of root galls, which inhibits the roots from absorbing soil nutrients and water. Sugar, the major source of carbon for all living organisms including pathogens and host plants, plays an important role in plant growth and development. OBJECTIVE: To explore the roles of BrSWEET2, BrSWEET13, and BrSWEET14 in P. brassicae resistance, Arabidopsis thaliana T-DNA knockout mutants sweet2, sweet13, and sweet14 were employed. METHODS: To isolate total RNA from the collected root nodules, the root tissues washed several times with running water and frozen tissues with liquid nitrogen. Total RNA was extracted using the Spectrum™ Plant Total RNA Kit (SIGMA) and cDNA was synthesized in a 20 µl reaction volume using the ReverTra Ace-α-® kit (TOYOBO). Real-time PCR was performed in a 10 µl reaction volume containing 1 µl of template DNA, 1 µl of forward primer, 1 µl of reverse primer, 5 µl of 2× iQTM SYBR® Green Supermix (BioRad), and 2 µl of sterile distilled water. The SWEET genes were genotyped using BioFACT™ 2× TaqBasic PCR Master Mix 2. RESULTS: Both sweet2 and sweet14 showed strong resistance to P. brassicae compared with wild-type Arabidopsis and Chinese cabbage plants and sweet13 mutant plants. Pathogenicity assays indicated that the SWEET2 gene plays an important role in clubroot disease resistance in higher plants.


Assuntos
Brassica rapa , Brassica , Plasmodioforídeos , Brassica rapa/genética , Plasmodioforídeos/genética , Brassica/genética , Água , RNA
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