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1.
Cancer Immunol Res ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38631019

RESUMO

The intrinsic pharmacokinetic limitations of traditional peptide-based cancer vaccines hamper effective cross-presentation and codelivery of antigens and adjuvants, which are crucial for inducing robust antitumor CD8+ T-cell responses. Here, we report the development of a versatile strategy that simultaneously addresses the different pharmacokinetic challenges of soluble subunit vaccines composed of antigens and CpG to modulate vaccine efficacy via translating an engineered chimeric peptide, eTAT, as an intramolecular adjuvant. Linking antigens to eTAT enhanced cytosolic delivery of the antigens. This, in turn, led to improved activation and lymph node-trafficking of antigen-presenting cells and antigen cross-presentation, thus promoting antigen-specific T-cell immune responses. Simple mixing of eTAT-linked antigens and CpG significantly enhanced codelivery of antigens and CpG to the antigen-presenting cells, and this substantially augmented the adjuvant effect of CpG, maximized vaccine immunogenicity and elicited robust and durable CD8+ T-cell responses. Vaccination with this formulation altered the tumor microenvironment and exhibited potent antitumor effects, with generally further enhanced therapeutic efficacy when used in combination with anti-PD1. Altogether, the engineered chimeric peptide-based orchestrated codelivery of antigen and adjuvant may serve as a promising but simple strategy to improve the efficacy of peptide-based cancer vaccines.

2.
Front Med ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38453818

RESUMO

Oncolytic virus (OV)-based immunotherapy has emerged as a promising strategy for cancer treatment, offering a unique potential to selectively target malignant cells while sparing normal tissues. However, the immunosuppressive nature of tumor microenvironment (TME) poses a substantial hurdle to the development of OVs as effective immunotherapeutic agents, as it restricts the activation and recruitment of immune cells. This review elucidates the potential of OV-based immunotherapy in modulating the immune landscape within the TME to overcome immune resistance and enhance antitumor immune responses. We examine the role of OVs in targeting specific immune cell populations, including dendritic cells, T cells, natural killer cells, and macrophages, and their ability to alter the TME by inhibiting angiogenesis and reducing tumor fibrosis. Additionally, we explore strategies to optimize OV-based drug delivery and improve the efficiency of OV-mediated immunotherapy. In conclusion, this review offers a concise and comprehensive synopsis of the current status and future prospects of OV-based immunotherapy, underscoring its remarkable potential as an effective immunotherapeutic agent for cancer treatment.

3.
Nat Commun ; 15(1): 9, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167274

RESUMO

PD-1 is a co-inhibitory receptor expressed by CD8+ T cells which limits their cytotoxicity. PD-L1 expression on cancer cells contributes to immune evasion by cancers, thus, understanding the mechanisms that regulate PD-L1 protein levels in cancers is important. Here we identify tumor-cell-expressed otubain-2 (OTUB2) as a negative regulator of antitumor immunity, acting through the PD-1/PD-L1 axis in various human cancers. Mechanistically, OTUB2 directly interacts with PD-L1 to disrupt the ubiquitination and degradation of PD-L1 in the endoplasmic reticulum. Genetic deletion of OTUB2 markedly decreases the expression of PD-L1 proteins on the tumor cell surface, resulting in increased tumor cell sensitivity to CD8+ T-cell-mediated cytotoxicity. To underscore relevance in human patients, we observe a significant correlation between OTUB2 expression and PD-L1 abundance in human non-small cell lung cancer. An inhibitor of OTUB2, interfering with its deubiquitinase activity without disrupting the OTUB2-PD-L1 interaction, successfully reduces PD-L1 expression in tumor cells and suppressed tumor growth. Together, these results reveal the roles of OTUB2 in PD-L1 regulation and tumor evasion and lays down the proof of principle for OTUB2 targeting as therapeutic strategy for cancer treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Linfócitos T Citotóxicos/metabolismo , Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Preparações Farmacêuticas/metabolismo , Tioléster Hidrolases/metabolismo
4.
J Hazard Mater ; 465: 133077, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38035525

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are a group of extremely carcinogenic organic pollutants. Our previous findings have demonstrated that plant roots actively take up PAHs through co-transport with H+ ions. Auxin serves as a pivotal regulator of plant growth and development. However, it remains unclear whether the hormone can enhance the uptake of PAHs by plant roots. Hence, the wheat root exposed to PAHs with/without auxins was set to investigate how the auxin promotes the PAHs uptake by roots. In our study, auxin could significantly enhance the uptake of PAHs after 4 h of exposure. After the addition of auxin, the root tissue cytoplasmic pH value was decreased and the H+ influx was observed, indicating that the extracellular space was alkalinized in a short time. The increased H+ influx rate enhanced the uptake of PAHs. In addition, the H+-ATPase activity was also increased, suggesting that auxin activated two distinct and antagonistic H+ flux pathways, and the H+ influx pathway was dominant. Our findings offer important information for exploring the mechanism underlying auxin regulation of PAHs uptake and the phytoremediation of PAH-contaminated soil and water.


Assuntos
Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Hidrocarbonetos Policíclicos Aromáticos/análise , Fenantrenos/metabolismo , Triticum/metabolismo , Concentração de Íons de Hidrogênio , Ácidos Indolacéticos , Poluentes do Solo/metabolismo , Raízes de Plantas/metabolismo
5.
Adv Mater ; 36(4): e2309732, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37971044

RESUMO

Gallium-based metallic liquids, exhibiting high theoretical capacity, are considered a promising anode material for room-temperature liquid metal alkali-ion batteries. However, electrochemical performances, especially the cyclic stability, of the liquid metal anode for alkali-ion batteries are strongly limited because of the volume expansion and unstable solid electrolyte interphase film of liquid metal. Here, the bottleneck problem is resolved by designing carbon encapsulation on gallium-indium liquid metal nanoparticles (EGaIn@C LMNPs). A superior cycling stability (644 mAh g-1 after 800 cycles at 1.0 A g-1 ) is demonstrated for lithium-ion batteries, and excellent cycle stability (87 mAh g-1 after 2500 cycles at 1.0 A g-1 ) is achieved for sodium-ion batteries by carbon encapsulation of the liquid metal anode. Morphological and phase changes of EGaIn@C LMNPs during the electrochemical reaction process are revealed by in situ transmission electron microscopy measurements in real-time. The origin for the excellent performance is uncovered, that is the EGaIn@C core-shell structure effectively suppresses the non-uniform volume expansion of LMNPs from ≈160% to 127%, improves the electrical conductivity of the LMNPs, and exhibits superior electrochemical kinetics and a self-healing phenomenon. This work paves the way for the applications of room-temperature liquid metal anodes for high-performance alkali-ion batteries.

6.
Environ Pollut ; 343: 123112, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38097155

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are a category of organic pollutants known for their high carcinogenicity. Our previous research has illustrated that plant roots actively absorb PAHs through a co-transport mechanism with H+ ions. Because auxin can increase the H+-ATPase activity, the wheat roots were exposed to PAHs with/without auxins to study whether auxins facilitate the uptake of PAHs by plant roots and to gain insights into the underlying mechanisms of this process. In our study, indole acetic acid (100 µM) and α-naphthaleneacetic acid (10 µM) significantly increased the PAHs concentrations in apoplast and symplast, and the treating time and concentrations were positively correlated with PAHs accumulations. The time-dependent kinetics for 36 h followed the Elovich equation, and the concentration-dependent kinetics of apoplastic and symplastic uptake for 4 h could be described with the Freundlich and Michaelis-Menten equations, respectively. The proportion of PAHs accumulated in apoplast could be enhanced by auxins in most treatments. Our findings offer novel insights into the mechanisms of PAH uptake by plant roots under auxin exposure. Additionally, this research aids in refining strategies for ensuring crop safety and improving phytoremediation of PAH-contaminated soil and water.


Assuntos
Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Plântula/química , Triticum , Raízes de Plantas/química , Poluentes do Solo/análise , Ácidos Indolacéticos
7.
Plant Physiol Biochem ; 206: 108275, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38103340

RESUMO

The study focuses on the uptake, accumulation, and translocation of polycyclic aromatic hydrocarbons (PAHs) in cereals, specifically exploring the role of peroxidase (UniProt accession: A0A3B5XXD0, abbreviation: PX1) and unidentified protein (UniProt accession: A0A3B6LUC6, abbreviation: UP1) in phenanthrene solubilization within wheat xylem sap. This research aims to clarify the interactions between these proteins and phenanthrene. Employing both in vitro and in vivo analyses, we evaluated the solubilization capabilities of recombinant transport proteins for phenanthrene and examined the relationship between protein expression and phenanthrene concentration. UP1 displayed greater transport efficiency, while PX1 excelled at lower concentrations. Elevated PX1 levels contributed to phenanthrene degradation, marginally diminishing its transport. Spectral analyses and molecular dynamics simulations validated the formation of stable protein-phenanthrene complexes. The study offers crucial insights into PAH-related health risks in crops by elucidating the mechanisms of PAH accumulation facilitated by transport proteins.


Assuntos
Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Proteínas de Transporte/metabolismo , Triticum/metabolismo , Raízes de Plantas/metabolismo , Fenantrenos/análise , Fenantrenos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo
8.
Contact Dermatitis ; 90(3): 201-210, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38148670

RESUMO

After almost three-quarters of a century during which contact dermatologists have often struggled to comprehend the relationship between metal allergy and failure of metal-alloy containing implant, it is possible to say that a relationship does exist, particularly for cobalt and chromium, but also for nickel. There is still debate as to whether allergy develops as a consequent of failure but thenceforth contributes to it, or whether sensitisation starts first and induces failure secondarily-opinion probably favours the first. Metal-on-polypropylene articulations were associated with few metal allergic problems but now are less favoured by orthopaedists due to plastic wear products causing osteolysis and pseudotumour formation through local inflammation. New metal alloys are regularly being introduced such that interested dermatologists need to stay on top of the situation. The jury is still out as to whether the recent favouring of titanium-containing alloys will confirm them to be more inert allergenically. Case reports do show some clinical reactions to titanium-containing implants and patch test series have inferred sometimes quite a high background rate of allergy, but interpretation must be tempered by the awareness that titanium salts on patch testing have a tendency to cause irritant reactions. Blood monitoring of metal ion values is now recommended in certain situations after joint replacement and increasing levels may be an indication that allergy with joint failure can develop, in which case patch testing is indicated, and suggested series are available. Predictive patch testing, whilst generally not recommended in the past, has been introduced into some protocols often by non-dermatologists, such that it is now needed for temporo-mandibular joint and Nuss bar insertion, and it can be anticipated that this may become more commonplace in the future. One of the major current deficits for patch testers is standardised guidance on which preparation or preparations to use for suspected titanium allergy. One suggestion is 0.5% titanium sulphate in petrolatum, though experience in at least one centre suggests the use of a battery of titanium salts might be desirable.


Assuntos
Dermatite Alérgica de Contato , Hipersensibilidade , Humanos , Titânio/efeitos adversos , Sais , Dermatite Alérgica de Contato/complicações , Ligas/efeitos adversos , Metais , Hipersensibilidade/etiologia
10.
J Exp Clin Cancer Res ; 42(1): 284, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891570

RESUMO

BACKGROUND: Oncolytic viruses are now well recognized as potential immunotherapeutic agents against cancer. However, the first FDA-approved oncolytic herpes simplex virus 1 (HSV-1), T-VEC, showed limited benefits in some patients in clinical trials. Thus, the identification of novel oncolytic viruses that can strengthen oncolytic virus therapy is warranted. Here, we identified a live-attenuated swine pseudorabies virus (PRV-LAV) as a promising oncolytic agent with broad-spectrum antitumor activity in vitro and in vivo. METHODS: PRV cytotoxicity against tumor cells and normal cells was tested in vitro using a CCK8 cell viability assay. A cell kinase inhibitor library was used to screen for key targets that affect the proliferation of PRV-LAV. The potential therapeutic efficacy of PRV-LAV was tested against syngeneic tumors in immunocompetent mice, and against subcutaneous xenografts of human cancer cell lines in nude mice. Cytometry by time of flight (CyTOF) and flow cytometry were used to uncover the immunological mechanism of PRV-LAV treatment in regulating the tumor immune microenvironment. RESULTS: Through various tumor-specific analyses, we show that PRV-LAV infects cancer cells via the NRP1/EGFR signaling pathway, which is commonly overexpressed in cancer. Further, we show that PRV-LAV kills cancer cells by inducing endoplasmic reticulum (ER) stress. Moreover, PRV-LAV is responsible for reprogramming the tumor microenvironment from immunologically naïve ("cold") to inflamed ("hot"), thereby increasing immune cell infiltration and restoring CD8+ T cell function against cancer. When delivered in combination with immune checkpoint inhibitors (ICIs), the anti-tumor response is augmented, suggestive of synergistic activity. CONCLUSIONS: PRV-LAV can infect cancer cells via NRP1/EGFR signaling and induce cancer cells apoptosis via ER stress. PRV-LAV treatment also restores CD8+ T cell function against cancer. The combination of PRV-LAV and immune checkpoint inhibitors has a significant synergistic effect. Overall, these findings point to PRV-LAV as a serious potential candidate for the treatment of NRP1/EGFR pathway-associated tumors.


Assuntos
Herpesvirus Suídeo 1 , Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Animais , Suínos , Camundongos , Vacinas Atenuadas , Camundongos Nus , Inibidores de Checkpoint Imunológico , Vírus Oncolíticos/genética , Receptores ErbB , Microambiente Tumoral
11.
Water Res X ; 21: 100197, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37655163

RESUMO

Various phosphorus (P)-inactivating materials with a strong capability of immobilizing P in sediment have been developed for lake geoengineering purposes to control internal P pollution. However, unsatisfactory applications have raised concerns about the reliability of the method. This study hypothesized that P migration from sediment to material is a key process regulating the immobilization, which is often neglected by common assessment procedures that assume that the material is closely in contact with sediment (e.g., as mixtures). To verify this hypothesis, 90-day incubation tests were conducted using drinking water treatment residue (DWTR). The results showed that the soluble P in the overlying water of sediment-DWTR mixtures and the mobile P in the mixtures were substantially reduced from the initial period and remained low during the whole incubation tests. However, assessment based on separated samples indicated a gradual P migration from sediment to DWTR for immobilization. Even after 90 days of incubation, mobile P still accounted for ∼5.33% of total P in the separated sediment. Further analysis suggested that using mixtures of sediment with DWTR accelerated P migration during the assessment, leading to a faster P immobilization assessment. Considering the relatively low levels of mobile P in the separated DWTR during incubation, the gradual decrease in mobile P in the separated sediment indicates that sediment P release regulates P immobilization efficiency. Therefore, designing a proper strategy to ensure sufficient time for the material to remain in close contact with the target sediment is critical to reducing uncertainties in lake geoengineering.

12.
Foods ; 12(15)2023 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-37569236

RESUMO

Coffee flavor considerably depends on the fermentation process, with contributing factors including fermentation temperature, oxygen concentration, and microbial diversity. Efficient controlling of the fermentation can improve the quality of coffee beverages. Therefore, several studies on coffee fermentation processes have been conducted in various regions. The objective of this study was to assess the microbial diversity of coffee beans undergoing anaerobic fermentation at various temperatures (4 °C or 37 °C) and fermentation durations (12 h or 36 h) using full-length 16S rRNA sequencing. This analysis aimed to evaluate the inhibitory effects of the fermented metabolites against ochratoxin-producing Aspergillus niger. From our results, Acetobacter was identified as the dominant microbial community at higher fermentation temperatures, whereas Leuconostoc and Gluconobacter were the dominant genera at lower temperatures. However, at lower temperatures, changes in microbial communities were relatively slow. This study expands our knowledge of the microbial diversity involved in the anaerobic fermentation of coffee beans in Taiwan. The findings of this study can be used in future research to cultivate microorganisms linked to the quality and improve the quality of coffee beverages through fermentation.

13.
Water Res ; 243: 120327, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37451125

RESUMO

The importance of controlling internal phosphorus (P) pollution in lakes has been recognized by scientists, and the application of P-inactivating materials to immobilize sediment P is often considered. However, sediment resuspension, a typical physical process occurring in lakes, has been demonstrated to increase the uncertainty of immobilization. In this study, we explored the characteristics of P immobilization in the horizontal direction under the effects of resuspension using annular flume tests based on drinking water treatment residuals (DWTR). The results showed that resuspension caused the mobile P and bioavailable P to be heterogeneously distributed in sediment planes after DWTR addition, resulting in varying P immobilization efficiencies at different depths. In particular, the coefficient of variation was 14.2-24.5% for mobile P horizontally distributed in the planes, resulting in a range of mobile P decreasing efficiencies at 24.0-47.8%. Further analysis indicated that variations in horizontal distribution were typically due to the varied migration of particles of different sizes. Specifically, P immobilization in sediment planes at different depths was regulated by promoting the migration of <8 µm DWTR after relatively low-intensity disturbance (in surface 0-1 cm sediment). After relatively high-intensity disturbance (in the whole 0-3 cm sediment), immobilization in the horizontal direction was regulated by coupling the migration of >63 µm DWTR (to the bottom) with the mixing of <8 µm DWTR in the sediment plane at different depths. The varying horizontal distributions of total P, resulting from the migration of 16-32 µm sediment, could enhance the heterogeneities of the P immobilization. Thus, the particle size of materials and lake background conditions, for example, the hydrodynamic characteristics and P distributions in differently sized sediments, should be used as key bases to select or develop P-inactivating materials to design proper remediation strategies for controlling internal P pollution in lakes.


Assuntos
Fósforo , Poluentes Químicos da Água , Sedimentos Geológicos , Poluentes Químicos da Água/análise , Eutrofização , Lagos
14.
FEBS J ; 290(20): 4921-4932, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37329190

RESUMO

Assembly of cell division protein FtsZ into the Z-ring at the division site is a key step in bacterial cell division. The Min proteins can restrict the Z-ring to the middle of the cell. MinC is the main protein that obstructs Z-ring formation by inhibiting FtsZ assembly. Its N-terminal domain (MinCN ) regulates the localization of the Z-ring by inhibiting FtsZ polymerization, while its C-terminal domain (MinCC ) binds to MinD as well as to FtsZ. Previous studies have shown that MinC and MinD form copolymers in vitro. This copolymer may greatly enhance the binding of MinC to FtsZ, and/or prevent FtsZ filaments from diffusing to the ends of the cell. Here, we investigated the assembly properties of MinCC -MinD of Pseudomonas aeruginosa. We found that MinCC is sufficient to form the copolymers. Although MinCC -MinD assembles into larger bundles, most likely because MinCC is spatially more readily bound to MinD, its copolymerization has similar dynamic properties: the concentration of MinD dominates their copolymerization. The critical concentration of MinD is around 3 µm and when MinD concentration is high enough, a low concentration MinCC could still be copolymerized. We also found that MinCC -MinD can still rapidly bind to FtsZ protofilaments, providing direct evidence that MinCC also interacts directly with FtsZ. However, although the presence of minCC can slightly improve the division defect of minC-knockout strains and shorten the cell length from an average of 12.2 ± 6.7 to 6.6 ± 3.6 µm, it is still insufficient for the normal growth and division of bacteria.


Assuntos
Proteínas de Escherichia coli , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Bactérias/metabolismo , Escherichia coli/metabolismo , Adenosina Trifosfatases/metabolismo , Divisão Celular , Proteínas de Membrana/metabolismo
15.
J Tradit Complement Med ; 13(3): 297-305, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37128194

RESUMO

Background and aim: Insomnia is a subjective illness that has been identified as a risk factor for dementia. In this study, we investigated the association of acupuncture treatment for insomnia with the risk of dementia. We collected data from the National Health Insurance Research Database (NHIRD) of Taiwan to analyze the incidence of dementia in patients with insomnia who received acupuncture treatment. Experimental procedure: This retrospective matched-cohort study included 152,585 patients, selected from the NHIRD, who were newly diagnosed with insomnia between 2000 and 2010. The follow-up period ranged from the index date to the date of dementia diagnosis, date of withdrawal from the insurance program, or December 31, 2013. A 1:1 propensity score method was used to match an equal number of patients (N = 18,782) in the acupuncture and non-acupuncture cohorts. We employed Cox proportional hazards models to evaluate the risk of dementia. The cumulative incidence of dementia in both cohorts was estimated using the Kaplan-Meier method, and the difference between them was assessed through a log-rank test. Results and conclusion: Patients with insomnia who received acupuncture treatment were observed to have a lower risk of dementia (adjusted hazard ratio = 0.54, 95% confidence interval = 0.50-0.60) than those who did not undergo acupuncture treatment. The cumulative incidence of dementia was significantly lower in the acupuncture cohort than in the non-acupuncture cohort (log-rank test, p < 0.001). The results suggest that acupuncture treatment significantly reduced or slowed the development of dementia in patients with insomnia.

16.
J Environ Manage ; 328: 117000, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36502704

RESUMO

The use of ceramsite to construct filtration systems (e.g., biofilters) is a common method for water treatment. To promote such applications, the development of low-cost, high-performance, and environmentally friendly ceramsites has received increasing attention from scientists, and a critical step in the development is the preparation of raw materials. As an inevitable and non-hazardous by-product during potable water production, drinking water treatment residue (DWTR) is typically recycled to make water treatment ceramsite to promote recycling in filtration systems. This study aims to bridge the knowledge gap regarding DWTR in making ceramsites for water treatment. The results suggest that the fabrication methods for DWTR-based ceramsite can be generally classified into sintering and non-sintering procedures. For the sintering method, owing to the heterogeneous properties (especially aluminum, iron, and calcium), DWTR has been applied as various sub-ingredients for raw materials preparations. In contrast, for the non-sintering method, DWTR is commonly applied as the main ingredient, and natural curing, physical crosslinking, and thermal treatment methods have been typically adopted to make ceramsite. However, DWTR-based ceramsites tend to have a high adsorption capability and favorable microbial effects to control different kinds of pollution (e.g., phosphorus, nitrogen, and organic matter). Future work is typically recommended to thoroughly evaluate the performance of DWTR-based ceramsite-constructed filtration systems to control water pollution concerning the making procedures, the potential to control pollution, the stability, and the safety of raw DWTR-based ceramsite, providing systematic information to design more proper planning for beneficial recycling.


Assuntos
Água Potável , Purificação da Água , Ferro , Alumínio , Purificação da Água/métodos
17.
J R Coll Physicians Edinb ; 52(4): 336-340, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36515578

RESUMO

In the Crimean War (1854-56), infamous for its high death rate from disease at 212 per thousand British troops annually - one third of which was due to cholera or dysentery - skin disease was common, accounting for 13% of all admissions and 4.2% of all deaths. Excluding typhus, skin disease caused 252 per thousand annual admissions and 8.8 per thousand annual deaths, with an overall case fatality of 3.4%. The commonest skin diseases were: localised cellulitis/abscess, ulcer, venereal disease, frostbite, scurvy, eruptive rashes and scabies. The biggest number of skin disease-related deaths were from frostbite and scurvy. Cutaneous afflictions with the highest case fatality were erysipelas (27%), gangrene (25%), smallpox (21%) and frostbite (19%). Problems from frostbite lessened during the better provisioned second winter. The experience of skin disease in the Crimea highlights the importance of public health and personal sanitation to skin health in the military context, and shows that skin-related infections and nutritional deficiencies easily develop if environmental conditions deteriorate.


Assuntos
Congelamento das Extremidades , Militares , Escorbuto , Dermatopatias , Humanos , Guerra da Crimeia , Dermatopatias/epidemiologia , Dermatopatias/etiologia
18.
Neuropsychiatr Dis Treat ; 18: 1895-1906, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36065385

RESUMO

Background: Migraine is a recurrent headache disease that has been identified as a risk factor for subsequent dementia. The present study collected data from Taiwan's National Health Insurance Research Database (NHIRD) to investigate the incidence of dementia in patients with migraine who did or did not concurrently receive acupuncture treatment. Methods: A 1:1 propensity score method was used to match an equal number of patients (N = 4813) in the acupuncture and nonacupuncture cohorts based on sex, age, migraine diagnosis year, index year, insurance amount, urbanization level, baseline comorbidities, and medication usage. We employed Cox proportional hazards models to evaluate the risk of dementia. Results: Patients with migraine who received acupuncture treatment were found to have a lower risk of dementia (adjusted hazard ratio [aHR] = 0.51, 95% CI = 0.40-0.65) than those who did not undergo acupuncture treatment. The cumulative incidence of dementia was significantly lower in the acupuncture cohort than in the nonacupuncture cohort (Log rank test, p < 0.001). This propensity score-matched cohort study demonstrated an association between acupuncture treatment and dementia development in patients with migraine in Taiwan. Conclusion: The results suggest that acupuncture treatment significantly reduced the development of dementia in patients with migraine.

19.
Antiviral Res ; 207: 105407, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36152816

RESUMO

Human rotaviruses (RVs) are the leading cause of severe diarrhea in infants and young children worldwide. Among the structural proteins, as a spike protein, rotavirus VP4 plays a key role in both viral attachment and penetration. Currently, studies on monoclonal antibodies (mAbs) against VP4 are limited. In this study, mice were immunized with truncated VP4* to produce murine mAbs. In total, 50 mAbs were produced and characterized. Twenty-four mAbs were genotype-specific and 20 mAbs recognized the common VP4 epitopes shared by P[8], P[4], and P[6] viruses. Thirty-five of the 50 mAbs were neutralizing mAbs, among which nine mAbs could neutralize all three P-genotype RVs, and 10 neutralizing mAbs exhibited conformational sensitivity. Ten mAbs recognized dominant neutralizing epitopes, including the broadly neutralizing mAb 9C4 recognized conformational epitope. Further investigation shows that S376 and S464 are key amino acids for 9C4 binding, however, the exact binding sites of 9C4 remain to be fully defined. Overall, this panel of mAbs has demonstrated utility as immunodiagnostic and research reagents, and could potentially serve as crucial tools for exploring the neutralizing mechanisms and quality control of VP4* protein-based RV subunit vaccines. Further evaluation of cross-neutralizing mAbs could not only improve the understanding of the heterotypic protection conferred by RV vaccines, but also facilitate the development of broadly protective RV vaccines.


Assuntos
Rotavirus , Aminoácidos , Animais , Anticorpos Monoclonais , Anticorpos Antivirais , Proteínas do Capsídeo/genética , Criança , Pré-Escolar , Epitopos , Humanos , Imunossupressores , Camundongos , Testes de Neutralização , Glicoproteína da Espícula de Coronavírus
20.
ACS Appl Mater Interfaces ; 14(33): 38196-38204, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-35951545

RESUMO

Soft devices, especially capacitive stress (or strain) sensors, are important for applications, including wearable medical monitoring, electronic skin, and soft robotics. The incorporation of liquid metal particles (LMPs) into highly deformable elastomers as inclusions ameliorates the mechanical compliance caused by a rigid filler. The high dielectric constant and liquid feature of LMPs are suitable for soft sensors with high sensitivity and a large real-time dynamic detection range. Here, a class of LM-elastomer composites are introduced with elastic and high dielectric properties, making them uniquely suitable for the application of soft stress sensors. The prepared stretchable soft stress sensor can detect the bending degree of the finger, monitor physiological signals in real time, and distinguish the vibration from the pronunciation of different letters. The nanoscale X-ray computational tomography (nano-CT) measurements indeed detect the changes of LMPs under stress, i.e., LMPs in the matrix distribute from uneven to relatively uniform, agglomerate, and even connect each other to have a conduction path in the composition with high LMP contents, which cause the changes in the physical properties of devices under operation. The cognition of LMP changes in composites under stress is instructive for promoting their further applications in the field of soft devices.


Assuntos
Elastômeros , Dispositivos Eletrônicos Vestíveis , Eletrônica , Metais , Monitorização Fisiológica
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