Mitochondria are dynamic organelles whose architecture changes depending on the cell’s energy requirements and other signalling events. These structural changes are collectively known as ...mitochondrial dynamics. Mitochondrial dynamics are crucial for cellular functions such as differentiation, energy production and cell death. Importantly, it has become clear in recent years that mitochondrial dynamics are a critical control point for immune cell function. Mitochondrial remodelling allows quiescent immune cells to rapidly change their metabolism and become activated, producing mediators, such as cytokines, chemokines and even metabolites to execute an effective immune response. The importance of mitochondrial dynamics in immunity is evident, as numerous pathogens have evolved mechanisms to manipulate host cell mitochondrial remodelling in order to promote their own survival. In this review, we comprehensively address the roles of mitochondrial dynamics in immune cell function, along with modulation of host cell mitochondrial morphology during viral and bacterial infections to facilitate either pathogen survival or host immunity. We also speculate on what the future may hold in terms of therapies targeting mitochondrial morphology for bacterial and viral control.
Mitochondrial dynamics is crucial for several cellular processes including immune cell function. This review discusses how modulation of host cell mitochondrial morphology affects pathogen survival and host immunity and speculates on related therapeutic approaches.
Herein, the effect of the insertion of a thin dielectric HfO2:Al2O3 (HAO) layer at different positions in the Pt/0.5Ba(Zr0.2Ti0.8)O3–0.5(Ba0.7Ca0.3)TiO3 (BCZT)/Au structure on the energy storage ...performance of the capacitors is investigated. A high storage performance is achieved through the insertion of a HAO layer between BCZT and Au layers. The insertion of the dielectric layer causes a depolarization field which results in a high linearity hysteresis loop with low energy dissipation. The Pt/BCZT/HAO/Au capacitors show an impressive energy storage density of 99.8 J cm−3 and efficiency of 71.0%, at an applied electric field of 750 kV cm−1. Further, no significant change in the energy storage properties is observed after passing 108 switching cycles through the capacitor. The presence of resistive switching (RS) in leakage current characteristics confirms the strong charge coupling between ferroelectric and insulator layers. The same trend of the RS ratio and the energy storage performance with the variation of the architecture of the devices suggests that the energy storage properties can be improved through the charge coupling between the layers. By combining ferroelectrics and dielectrics into one single structure, the proposed strategy provides an efficient way for developing highly efficient energy storage capacitors.
It is demonstrated that high‐performance energy storage devices can be achieved through integration of ferroelectric and dielectric thin films and can be further optimized through selection of proper architecture of the device. The Pt/BCZT/HAO/Au capacitors exhibit an energy storage density of 99.8 J cm−3 and efficiency of 71.0%, with no significant change in the energy storage properties observed after passing 108 switching cycles.
Objective
In current management paradigms of rheumatoid arthritis (RA), patient global assessment (PGA) is crucial to decide whether a patient has attained remission (target) or needs reinforced ...therapy. We investigated whether the clinical and psychological determinants of PGA are appropriate to support this important role.
Methods
This was a cross‐sectional, single‐center study including consecutive ambulatory RA patients. Data collection comprised swollen 28‐joint count (SJC28), tender 28‐joint count (TJC28), C‐reactive protein (CRP) level, PGA, pain, fatigue, function, anxiety, depression, happiness, personality traits, and comorbidities. Remission was categorized using American College of Rheumatology/European League Against Rheumatism Boolean‐based criteria: remission, near‐remission (only PGA >1), and nonremission. A binary definition without PGA (3v‐remission) was also studied. Univariable and multivariable analyses were used to identify explanatory variables of PGA in each remission state.
Results
A total of 309 patients were included (remission 9.4%, near‐remission 37.2%, and nonremission 53.4%). Patients in near‐remission were indistinguishable from remission regarding disease activity, but described a disease impact similar to those in nonremission. In multivariable analyses, PGA in near‐remission was explained (R2adjusted = 0.50) by fatigue, pain, anxiety, and function. Fatigue and pain had no relationship with disease activity measures.
Conclusion
In RA, a consensually acceptable level of disease activity (SJC28, TJC28, and CRP level ≤1) does not equate to low disease impact: a large proportion of these patients are considered in nonremission solely due to PGA. PGA mainly reflects fatigue, pain, function, and psychological domains, which are inadequate to define the target for immunosuppressive therapy. This consideration suggests that clinical practice should be guided by 2 separate remission targets: inflammation (3v‐remission) and disease impact.
Chronic skin wounds are the leading cause of nontraumatic foot amputations worldwide and present a significant risk of morbidity and mortality due to the lack of efficient therapies. The intrinsic ...characteristics of hydrogels allow them to benefit cutaneous healing essentially by supporting a moist environment. This property has long been explored in wound management to aid in autolytic debridement. However, chronic wounds require additional therapeutic features that can be provided by a combination of hydrogels with biochemical mediators or cells, promoting faster and better healing. We survey hydrogel-based approaches with potential to improve the healing of chronic wounds by reviewing their effects as observed in preclinical models. Topics covered include strategies to ablate infection and resolve inflammation, the delivery of bioactive agents to accelerate healing, and tissue engineering approaches for skin regeneration. The article concludes by considering the relevance of treating chronic skin wounds using hydrogel-based strategies.
Tuberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, has recently joined HIV/AIDS as the world's deadliest infectious disease, affecting around 9.6 million people ...worldwide in 2014. Of those, about 1.2 million died from the disease. Resistance acquisition to existing antibiotics, with the subsequent emergence of Multi-Drug Resistant mycobacteria strains, together with an increasing economic burden, has urged the development of new anti-TB drugs. In this scope, antimicrobial peptides (AMPs), which are small, cationic and amphipathic peptides that make part of the innate immune system, now arise as promising candidates for TB treatment. In this review, we analyze the potential of AMPs for this application. We address the mechanisms of action, advantages and disadvantages over conventional antibiotics and how problems associated with its use may be overcome to boost their therapeutic potential. Additionally, we address the challenges of translational development from benchside to bedside, evaluate the current development pipeline and analyze the expected global impact from a socio-economic standpoint. The quest for more efficient and more compliant anti-TB drugs, associated with the great therapeutic potential of emerging AMPs and the rising peptide market, provide an optimal environment for the emergence of AMPs as promising therapies. Still, their pharmacological properties need to be enhanced and manufacturing-associated issues need to be addressed.
The basis invariant flavor puzzle Bento, Miguel P.; Silva, João P.; Trautner, Andreas
The journal of high energy physics,
01/2024, Letnik:
2024, Številka:
1
Journal Article
Recenzirano
Odprti dostop
A
bstract
The flavor puzzle of the Standard Model quark sector is formulated in a non-perturbative way, using basis invariants that are independent of the choice of quark field basis. To achieve ...this, we first derive the algebraic ring of 10 CP even (primary) and 1 CP odd (secondary) basis invariants, using the Hilbert series and plethystic logarithm. An orthogonal basis in the ring of basis invariants is explicitly constructed, using hermitian projection operators derived via birdtrack diagrams. The thereby constructed invariants have well defined CP transformation behavior and give the most direct access to the flavor symmetric alignments of basis covariants. We firstly “measure” the orthogonal basis invariants from experimental data and characterize their location in the available parameter space. The experimentally observed orthogonal basis invariants take very close to maximal values and are highly correlated. Explaining the location of the invariants at close to maximal points, including the associated miniscule and highly correlated deviations, corresponds to solving the flavor puzzle in the invariant language. Once properly normalized, the orthogonal basis invariants are close to scale (RGE) invariant, hence, provide exquisite targets for fits of both, low- and high-scale (bottom-up and top-down) flavor models. Our result provides an entirely new angle on the flavor puzzle, and opens up ample opportunities for its ultimate exploration.
Egypt is the most affected nation by hepatitis C virus (HCV) and needs a comprehensive characterization of HCV epidemiology to inform the scale-up of treatment and prevention programs. Systematic ...reviews, meta-analyses, and meta-regressions were conducted. A total of 25 incidence, 259 prevalence, and 47 genotype studies were identified. Incidence and prevalence levels were high across all populations. Genotype 4 accounted for 94.1% of infections with a relative Shannon Diversity Index of only 14.4%. Pooled mean HCV prevalence was estimated at 11.9% (95% CI = 11.1-12.6%) among the general population, 55.6% (95% CI = 49.4-61.7%) among populations at high risk, 14.3% (95% CI = 10.3-18.8%) among populations at intermediate risk, 56.0% (95% CI = 50.4-61.6%) among populations with liver-related conditions, and 35.0% (95% CI = 27.3-43.1%) among special clinical populations. Mean HCV viremic rate was estimated at 66.7% (95% CI = 61.7-71.5%). Meta-regression indicated 6% lower odds for HCV prevalence for each one-year increment in publication year (AOR = 0.94; 95% CI = 0.92-0.96). HCV prevalence is high with evidence for ongoing transmission mainly through healthcare. Genotype diversity is low with genotype 4 dominance. Two-thirds of antibody-positive Egyptians are chronically infected and need treatment. Clinical populations should be prioritized for screening. Despite the large-scale epidemic, prevalence appears to be declining rapidly consistent with a contracting epidemic.
Despite the increasing use of pesticides in tropical countries, research and legislative efforts have focused on their temperate counterparts. This paper presents a review of the literature on ...environmental risk assessment of pesticides for tropical terrestrial agroecosystems. It aims at evaluating potential differences in pesticide risk between temperate and tropical regions as well as to highlight research needs in the latter. Peculiarities of pesticide risks in tropical terrestrial agroecosystems are discussed in subsections 1) agricultural practices; 2) research efforts; 3) fate and exposure; 4) toxicity testing methods; and 5) sensitivity. The intensive and often inadequate pesticide application practices in tropical areas are likely to result in a relatively greater pesticide exposure in edge-of-field water bodies. Since pesticide fate may be different under tropical conditions, tropical scenarios for models estimating predicted environmental pesticide concentrations should be developed. Sensitivity comparisons do not indicate a consistent similar, greater or lower relative sensitivity of tropical soil organisms as compared to temperate organisms. However, several methods and procedures for application in the tropics need to be developed, which include: 1) identifying and collecting natural soils to be used as reference test substrates in tests; 2) identifying and discerning the range of sensitivity of native test species to soil contaminants; 3) developing test guidelines applicable to tropical/subtropical conditions; and 4) developing methods and procedures for higher tier testing for full development and implementation of environmental risk assessment schemes.
•Peculiarities of pesticide risk in tropical terrestrial ecosystems were reviewed.•Pesticide exposure in the tropics is high due to intensive agricultural practices.•Research and legislative efforts in the tropics are insufficient.•Pesticide fate and toxicity may be different in different climatic zones.•Pesticide risk assessment schemes need to be adjusted to tropical conditions.
Commercially pure magnesium was processed by severe plastic deformation techniques and thermo-mechanical routes to produce samples with grain sizes in the range from 1.0 to 300 µm. Tensile testing of ...a fine-grained material revealed a decrease in hardening and an increase in strain rate sensitivity with decreasing testing strain rate from 10⁻² to 10⁻⁷ s⁻¹. Compression testing of fine-grained samples not only revealed similar trend, but also there was a transition from twinning to slip-dominated flow. Dynamic ultra-microhardness testing showed an increase in strain rate sensitivity with decreasing grain size. The trend of decreasing hardening rate and increasing strain rate sensitivity with decreasing strain rate was not observed in samples with a coarser grain size. Compression testing at different temperatures suggests that a creep mechanism with stress exponent of ~7 and activation energy close to grain boundary diffusion operates at low strain rates and moderate temperatures. A model for a new deformation mechanism is proposed based on the present experimental results and published data.
Gasification is a thermochemical process to convert the biomass chemical energy into a gaseous fuel, which is a suitable renewable energy source as a substitute for fossil fuel. Research on this ...technology has been developed to improve its efficiency and syngas quality. Computational modeling of the gasification process is an advantageous tool for predicting a complex process reducing actual experiments. This paper aims to present an updated review of application of stoichiometric thermodynamic equilibrium model that was widely investigated on the scientific literature. Due to its limitations in being based on ideal theoretical conditions, some authors modified the model based on experimental data to obtain more accurate results. The review presented in this work comprehends explaining the method of model implementation highlighting main modifications proposed by authors. The importance of this study is that the extensive literature review of model modifications provides a better understanding of gasification modeling that may serve as a basis for future research. In this way, further works will be able to develop new approaches for this model, contributing to the scientific knowledge of the area. As result of this research it was possible to point out as main modifications the following topics: to include tar and/or char; and to force the change in the equilibrium of reactions through the application of multiplication factors to equilibrium constants. It was proved that modified models predict the gas composition much closer to the experimental value than the basic model.
•The stoichiometric thermodynamic equilibrium model developments were reviewed.•Modifications of model based on experimental data improve prediction accuracy.•Reviewed modified models may include tar and/or char yields.•Reviewed modified models may use artifices to affect equilibrium of reactions.
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