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This paper combines the nine-factor model with the construction of university think tanks, establishes the strategic positioning of university think tanks, analyzes the methods and measures of cultivating leading talents and innovative talents in university think tanks and classifies the influence of university think tanks into decision-making influence, elite influence and popular influence. Based on the analysis of big data and concerning the fuzzy hierarchical analysis method, the evaluation model of information service quality of university think tanks has been established. The evaluation indexes of the information platform of university think tanks are divided into four indexes: service resources, service content, webpage technology, and service effect. According to the constructed evaluation indexes, two-by-two comparisons are made between each index to obtain the score of the importance of each index. Based on fuzzy mathematics, the qualitative evaluation can be transformed into quantitative evaluation according to the principle of affiliation degree to arrive at the evaluation grade of the information platform capacity of university think tanks and innovative talents.

Ferrites were prepared using the oxide method with strontium carbonate (SrCO3), zinc oxide (ZnO), cobalt trioxide (CO3O4), and iron oxide (Fe2O3) as raw materials. The effects of sintering temperature on the phase composition, microstructure, particle size and porosity, intrinsic coercivity Hcj, saturation magnetization Ms and electromagnetic parameters of W-type ferrite absorbent were studied. The results show that W-type ferrite is not formed when the sintering temperature is 1 125 °C. When the sintering temperature is 1 175 °C, lamellar W-type ferrite is formed. At 1 225 °C and 1 275 °C, the prepared W-type ferrite absorbent shows better absorbing properties. [ABSTRACT FROM AUTHOR]

An efficient and versatile synthesis of alcohols via transfer hydrogenation from ketones with isopropanol, utilizing [Ni(6,6′‐(OH)2‐2,2′‐bpy)][Br2] under alkaline conditions, has been documented. It was noteworthy that many readily reducible or labile functional groups such as nitro, cyano, and halide, within the same molecular framework, did not undergo any change under the standard reaction conditions. Furthermore, the gram scale transfer hydrogenation reaction was successfully carried out with good yield using a common route with only a single purification by column chromatography. [ABSTRACT FROM AUTHOR]

Fe3+ is a promising dopant for designing near‐infrared (NIR) phosphors due to its broadband emitting, non‐toxic, and inexpensive properties. However, the 4E (4D) and 4E + 4A1 (4G) levels of Fe3+ ions are independent of the crystal‐field parameter, and the spectral regulation has become a huge challenge. Herein, a broadband NIR‐emitting phosphor Ca2.5Hf2.5(Ga, Al)3O12: Fe3+ is successfully developed toward long‐wave ultraviolet (LWUV) light‐pumped NIR phosphor‐converted LED (pc‐LED). Significantly, the excited transition reverse of Ca2.5Hf2.5Ga3O12: Fe3+ can be realized by simply adjusting Fe3+ concentration, which results in the largely enhanced excitation around 410 nm and matches well with the commercial LWUV LED. Moreover, Ca2.5Hf2.5Ga3O12: Fe3+ can exhibit a broadband NIR emission centered at 770 nm with optimized doping content at 0.01 mol%, which are demonstrated to ascribe to Fe3+ occupying both octahedral Hf 4+ and tetrahedral Ga3+ sites. Further, a simple cation modulation strategy is proposed to successfully break the lattice symmetry around Fe3+ ions and largely enhance the NIR‐emission intensity to 200% as much as before. Finally, a NIR pc‐LED is fabricated by employing Ca2.5Hf2.5Ga3O12: Fe3+, Al3+ coating on a 410 nm LED chip, which shows great potential in non‐destructive inspection applications. [ABSTRACT FROM AUTHOR]

Fast optical modulation of nanoplasmonics is fundamental for on-chip integration of all-optical devices. Although various strategies have been proposed for dynamic modulation of surface plasmons, critical issues of device compatibility and extremely low efficiency in the visible spectrum hamper the application of optoplasmonic nanochips. Here we establish an optoplasmonic system based on Au@Cu2–xS hybrid core–shell nanoparticles. The optical excitation of hot electrons and their charge transfer to the semiconductor coating (Cu2–xS) lead to lowered electron density of Au, which results in the red shift of the localized surface plasmon resonance. The hot electrons can also transport through the Cu2–xS layer to the metal substrate, which increases the conductance of the nanogap. As such, the coupled gap plasmon blue-shifts with a magnitude of up to ∼15 nm, depending on the excitation power and the thickness of the coatings, which agrees with numerical simulations. All of this optoelectronic tuning process is highly reversible, controllable and fast with a modulated laser beam, which is highly compatible and sufficiently useful for on-chip integration of nanophotonic devices. [ABSTRACT FROM AUTHOR]

The concrete-filled steel tubular (CFST) arch bridge has achieved significant development in recent years due to its unique mechanical performance and technical advantages. However, due to the lagging theoretical research compared to engineering practice, many problems have been exposed in the existing bridges, resulting in adverse social impacts and enormous economic losses. With the increasing prominence of safety issues in CFST arch bridges, it is necessary to assess their safety condition in service. This paper establishes a safety assessment index system for CFST arch bridges using the fuzzy analytic hierarchy process (AHP) based on an exponential scale. The assessment method proposed includes the following main points: (1) Bridge safety assessment is closely related to the load-bearing capacity of components. This study proposes an assessment index that comprehensively considers both the defect conditions and the design load-bearing capacity of components for the safety assessment. (2) The exponential scale method is introduced to safety assessment for the first time, and the AHP based on an exponential scale is applied to calculate the component weights. (3) Considering the specific structural characteristics of CFST arch bridges, this study provides a detailed division of component types and calculates the component weights. By combining the component assessment indexes, a comprehensive safety assessment index system is established, and a safety assessment method for CFST arch bridges is proposed. (4) Taking the Jiantiao Bridge in Zhejiang Province as an engineering case, the load-bearing capacity of components is calculated using finite element software ANSYS 19.1. Based on the established safety assessment index system, the safety of the bridge is assessed by integrating the inspection results. (5) Software for the safety assessment of a CFST arch bridge is developed using Visual Basic, and the assessment results align well with the actual condition of the bridge. [ABSTRACT FROM AUTHOR]

Mechanoluminescent materials are characterized by high luminescence intensity, high repeatability, no external voltage activation, and a good linear relationship between stress and mechanoluminescence intensity within a certain range. Therefore, mechanoluminescent materials have attracted increasing attention from researchers in the fields of stress sensing, encryption and anti-counterfeiting, structural health monitoring, energy-saving lighting, intelligent wearable devices, and other fields. In this study, ZnS:Mn powders with different Mn 2+ ratios and different ion doping were synthesized by a high-temperature solid-phase reaction, and the synthesis of various materials was characterized. Then, the optimal mechanoluminescence effect of the ZnS:1%Mn,1%Li material was obtained. The photoluminescence intensity of ZnS:1%Mn,1%Li was 16.7 times higher than that of the sample without doping with Li + , and the mechanoluminescence intensity was 1.64 times higher. Finally, polyethylene terephthalate (PET) film was combined with ZnS:Mn,Li mechanoluminescent powders to prepare flexible three-layer composite film. Based on this, a feasible strategy for the detection of temporomandibular disorders was proposed. The composite film is easy to use, economical, and safe, and has good mechanoluminescent performance, which has potential application value in the field of occlusal force detection and visualization., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

The Permian (∼260 Ma) Song Da volcanic suite in Vietnam is one of very few known occurrences of Phanerozoic ultramafic volcanic rocks that are similar in composition to komatiites. Despite continuous efforts to determine the primary melt composition of Song Da ultramafic lavas, the concentrations of the volatile and fluid-mobile elements are still poorly constrained due to widespread alteration and low-grade metamorphism of bulk rocks. This study reports high-precision in-situ major- and trace element abundances in host olivine and inclusions of melt and Cr-spinel from the Song Da ultramafic lavas. Two different types were identified: low-Ti lavas, previously described as komatiites, and newly discovered Ti- and Na-rich picrites. The application of olivine-melt Sc/Y, olivine-spinel Al, and olivine-melt Fe/Mg geothermometers indicates crystallization temperatures of up to 1450 °C for the Song Da low-Ti suite, which are within the range of komatiite crystallization temperatures, and up to 1330 °C for the high-Ti picrites. These conditions correspond to mantle potential temperatures of 1590 °C and 1450 °C, respectively. The estimation of oxygen fugacity, based on V partitioning between olivine and melt and Fe2+/Fe3+ between spinel and melt, indicates that low-Ti melts crystallized in a closed system under reducing conditions starting from one to half an order of magnitude below the QFM buffer. The high-Ti melt crystallized at higher oxygen fugacity (∆QFM +0.5) in a buffered open system. The primary melt of the Song Da komatiites contained 0.7 wt% H 2 O, which was likely entrained from the hydrated Mantle Transition Zone (MTZ) by a partially molten plume. Our results indicate that the Song Da low-Ti ultramafic volcanics were likely derived from an ultramafic komatiite-like parental melt with an MgO content between 21 and 23 wt%. It was produced by a high degree (>26%) of partial melting of a depleted mantle source. The high-Ti picrite melt had 17–18 wt% MgO and was produced by a lower degree of partial melting (<9%) in a colder part of the same plume. • Studied Low-Ti (LTi) and High-Ti (HTi) ultramafic lavas are part of Emeishan LIP. • LTi and HTi crystalize from 1450 and 1330 °C at QFM-0.5 and NNO buffers respectively. • LTi parental melt has a komatiite composition with 22 wt% MgO and 0.7 wt% H 2 O. • HTi parental melt is alkaline with 17 wt% MgO, high LREE and Na, and low in HREE. • Primary melts form in mantle plume at Tp of 1590 °C (LTi) and 1450 °C (HTi). [ABSTRACT FROM AUTHOR]

We propose a flexible functional varying-coefficient single-index quantile regression model where the functional covariates of the linear part have time-varying coefficients and the single-index component offers great model flexibility in data analysis while circumventing the curse of dimensionality. The proposed model includes many existing quantile regression models for functional/longitudinal data as special cases. We use B-splines to estimate the link and coefficient functions. Under some mild conditions, we establish the asymptotic normality of the estimated index parameter vector, and obtain the convergence rates of the estimated link and coefficient functions. Moreover, we propose a score test to examine whether the effects of some covariates on the functional response are time-varying. Finally, we provide some numerical studies including Monte Carlo simulations and an empirical application to illustrate the proposed method. [ABSTRACT FROM AUTHOR]

Background: Metabolic clusters can stratify subgroups of individuals at risk for type 2 diabetes mellitus and related complications. Since obesity and insulin resistance are closely linked to alterations in hemostasis, we investigated the association between plasmatic coagulation and metabolic clusters including the impact on survival. Methods: Utilizing data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, we assigned 917 participants without diabetes to prediabetes clusters, using oGTT-derived glucose and insulin, high-density lipoprotein cholesterol, triglycerides, and anthropometric data. We performed a comprehensive analysis of plasmatic coagulation parameters and analyzed their associations with mortality using proportional hazards models. Mediation analysis was performed to assess the effect of coagulation factors on all-cause mortality in prediabetes clusters. Results: Prediabetes clusters were assigned using published tools, and grouped into low-risk (clusters 1,2,4; n = 643) and high-risk (clusters 3,5,6; n = 274) clusters. Individuals in the high-risk clusters had a significantly increased risk of death (HR = 1.30; CI: 1.01 to 1.67) and showed significantly elevated levels of procoagulant factors (fibrinogen, FVII/VIII/IX), D-dimers, von-Willebrand factor, and PAI-1, compared to individuals in the low-risk clusters. In proportional hazards models adjusted for relevant confounders, elevated levels of fibrinogen, D-dimers, FVIII, and vWF were found to be associated with an increased risk of death. Multiple mediation analysis indicated that vWF significantly mediates the cluster-specific risk of death. Conclusions: High-risk prediabetes clusters are associated with prothrombotic changes in the coagulation system that likely contribute to the increased mortality in those individuals at cardiometabolic risk. The hypercoagulable state observed in the high-risk clusters indicates an increased risk for cardiovascular and thrombotic diseases that should be considered in future risk stratification and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Oxidative damage resulting from weaning stress significantly impacts the growth performance and health status of piglets. Taurine, a dietary antioxidant with diverse functions, was investigated in this study for its protective role against weaning stress-induced oxidative damage and its underlying mechanism. Forty 28-day-old male castrated weaned piglets were randomly assigned to four groups. The control group received the basal diet, while the experimental groups were fed the basal diet supplemented with 0.1, 0.2%, or 0.3% taurine over a 28-day period. In vitro, H2O2 was utilized to induce oxidative damage to the jejunal mucosa of piglets via IPEC-J2 cells. The results demonstrated that taurine supplementation reduced the incidence of diarrhea in piglets compared to that in the control group (p < 0.05); the addition of 0.2 and 0.3% taurine led to increased average daily gain and improved feed conversion efficiency in weaned piglets, showing a linear dose-response correlation (p < 0.05). Taurine supplementation at 0.2 and 0.3% enhanced the activities of serum CAT and GSHPx while decreasing the levels of serum NO, XOD, GSSG, and MDA (p < 0.05). Moreover, it significantly elevated the levels of GSS, Trx, POD, complex I, mtnd5, and mt-nd6, enhancing superoxide anion scavenging capacity and the hydroxyl-free scavenging rate in the livers of weaned piglets while reducing NO levels in the liver (p < 0.05). Additionally, 0.2 and 0.3% taurine supplementation decreased serum IL-6 levels and elevated the concentrations of IgA, IgG, and IL-10 in weaned piglets (p < 0.05). The levels of occludin, claudin, and ZO-1 in the jejunum mucosa of weaned piglets increased with 0.2 and 0.3% taurine supplementation (p < 0.05). In IPEC-J2 cells, pretreatment with 25 mM taurine for 24 h enhanced the activities of SOD and CAT; reduced the MDA content; upregulated the mRNA expression of various genes, including ZO-1, occludin, claudin-1, Nrf2, and HO-1; and reversed the oxidative damage induced by H2O2 exposure (p < 0.05). Overall, the findings suggest that the inclusion of 2 and 3% taurine in the diet can enhance growth performance, reduce diarrhea rates, ameliorate oxidative stress and inflammation, and promote intestinal barrier function in weaned piglets. [ABSTRACT FROM AUTHOR]

Background: Body composition is recognized to be associated with clinical outcomes in patients with locally advanced rectal cancer (LARC). This study aimed to determine the prognostic role of regional adipose tissue distribution in patients with resectable LARC treated with or without neoadjuvant chemoradiotherapy (nCRT). Methods: This retrospective study included 281 consecutive patients who underwent radical surgery for LARC with or without preoperative nCRT between 2013 and 2019. Patients underwent contrast-enhanced CT scans before nCRT and before surgery. Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and gluteal subcutaneous adipose tissue (gSAT) were quantified on the CT images. The association of adipose tissue distribution with progression-free survival (PFS) was analyzed using Cox proportional hazards analysis. Results: A total of 102 nCRT-treated and 179 primarily resected patients were included. During a median follow-up period of 24 months, 74 (26.3%) patients experienced local recurrence or metastasis. Multivariable analysis showed that VAT was associated with PFS in all patients (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.04-1.57; P = 0.021). This association was only maintained in primarily resected patients (HR 1.31, 95% CI 1.02-1.69; P = 0.037). For patients receiving preoperative nCRT, VAT was not significantly associated with PFS, while the dynamic change in gSAT (ΔgSAT) between nCRT and surgery was associated with PFS (HR 0.43, 95%CI 0.27-0.69, P = 0.001). Conclusion: Visceral obesity is an adverse prognostic factor in patients with resectable LARC treated by primary resection, while increased gluteal subcutaneous adiposity during preoperative nCRT may indicate favorable clinical outcomes. [ABSTRACT FROM AUTHOR]

Freezing temperatures are a severe issue in North Florida, primarily due to occasional cold snaps and frost events in winter and early spring that cause damage to citrus groves, resulting in reduced fruit yield. The apoplasm is the primary cell component that interacts with environmental stress and is essential for plant tolerance to freezing temperatures. The present study was conducted to gain insight into how the application of silicon (Si) and potassium (K) are involved in the leaf apoplasm contributes to freezing stress tolerance, and regulates carbohydrate metabolism. We used Satsuma mandarin (Citrus unshiu Marc.), the most successful commercially grown citrus cultivar in North Florida, and treated trees with two concentrations of Si and K (50 and 100 ppm) both individually and combined as foliar spray to determine their effect as they relate to improving cold hardiness. Freezing stress (-6 °C) caused a severe reduction in photosynthesis, and modulations in leaf carbohydrate metabolism resulted in inhibited plant growth. The exogenous application of Si and K both improved the photosynthesis rate, soluble sugars, and activities of enzymes of carbohydrate metabolism such as fructokinase, phosphofructokinase, hexokinase, sucrose and phosphate synthase, and acid and neutral invertase. Applying Si (100 ppm) and combined treatment (Si + K-50) showed the best response by inducing the maximum tolerance to freeze stress. Our data demonstrated the ameliorative effect of Si and K under freezing stress in citrus is associated with modification in carbohydrate metabolism in the leaf apoplasm. This study provides direction for future research to investigate the effect of Si and K on the transcriptome and metabolome in citrus plants and their tissues under freezing stress. [ABSTRACT FROM AUTHOR]

The limited arsenal of antifungal drugs have prompted the search for novel molecules with biological activity. This study aimed to characterize the antifungal mechanism of action of Eugenia uniflora extract and its synergistic activity with commercially available antifungal drugs on the following Candida species: C. albicans, C. tropicalis, C. glabrata, C. parapsilosis and C. dubliniensis. In silico analysis was performed to predict antifungal activity of the major compounds present in the extract. Minimal inhibitory concentrations (MICs) were determined in the presence of exogenous ergosterol and sorbitol. Yeast cells were grown in the presence of stressors. The loss of membrane integrity was assessed using propidium iodide staining (fluorescence emission). Synergism between the extract and antifungal compounds (in addition to time kill-curves) was determined. Molecular docking revealed possible interactions between myricitrin and acid gallic and enzymes involved in ergosterol and cell wall biosynthesis. Candida cells grown in the presence of the extract with addition of exogenous ergosterol and sorbitol showed 2 to 8-fold increased MICs. Strains treated with the extract revealed greater loss of membrane integrity when compared to their Fluconazole counterparts, but this effect was less pronounced than the membrane damage caused by Amphotericin B. The extract also made the strains more susceptible to Congo red and Calcofluor white. A synergistic action of the extract with Fluconazole and Micafungin was observed. The E. uniflora extract may be a viable option for the treatment of Candida infections. [ABSTRACT FROM AUTHOR]

Abnormal glucose metabolism in microglial is closely associated with Alzheimer's disease (AD). Reprogramming of microglial glucose metabolism is centered on regulating the way in which microglial metabolize glucose to alter microglial function. Therefore, reprogramming microglial glucose metabolism is considered as a therapeutic strategy for AD. Huanshaodan (HSD) is a Chinese herbal compound which shows significant efficacy in treating AD, however, the precise mechanism by which HSD treats AD remains unclear. This study is aim to investigate whether HSD exerts anti-AD effects by regulating the metabolic reprogramming of microglial through the mTOR/HIF-1α signaling pathway. SAMP8 mice and BV2 cells were used to explore the alleviative effect of HSD on AD and the molecular mechanism in vivo and in vitro. The pharmacodynamic effects of HSD was evaluated by behavioral tests. The pathological deposition of Aβ in brain of mice was detected by immunohistochemistry. ELISA method was used to measure the activity of HK2 and the expression of PKM2, IL-6 and TNF-α in hippocampus and cortex tissues of mice. Meanwhile, proteins levels of p-mTOR, mTOR, HIF-1α, CD86, Arg1 and IL-1β were detected by Western-blot. LPS-induced BV2 cells were treated with HSD-containing serum. The analysis of the expression profiles of the CD86 and CD206 markers by flow cytometry allows us to distinguish the BV2 polarization. Glucose, lactic acid, ATP, IL-6 and TNF-α levels, as well as lactate dehydrogenase and pyruvate dehydrogenase activities were evaluated in the BV2. Western-blot analysis was employed to detect mTOR, p-mTOR, HIF-1α and IL-1β levels in BV2. And the mTOR agonist MHY1485 (MHY) was chosen to reverse validate. In this study, it is found that HSD improved cognitive impairment in SAMP8 mice and reduced Aβ deposition, suppressed the levels of glycolysis and neuroinflammation in mice. In LPS-induced BV2 cells, HSD also regulated glycolysis and neuroinflammation, and suppressed the mTOR/HIF-1α signaling pathway. More importantly, these effects were reversed by MHY. It is demonstrated that HSD regulated microglial glucose metabolism reprogramming by inhibiting the mTOR/HIF-1α signaling pathway, alleviated neuroinflammation, and exerted anti-AD effects. This study provided scientific evidence for the clinical application of HSD for treating AD. [ABSTRACT FROM AUTHOR]

More than two million people worldwide are affected by life-threatening, invasive fungal infections annually. Candida species are the most common cause of nosocomial, invasive fungal infections and are associated with mortality rates above 40%. Despite the increasing incidence of drug-resistance, the development of novel antifungal formulations has been limited. Here we investigate the antifungal mode of action and therapeutic potential of positively charged, synthetic peptide mimics to combat Candida albicans infections. Our data indicates that these synthetic polymers cause endoplasmic reticulum stress and affect protein glycosylation, a mode of action distinct from currently approved antifungal drugs. The most promising polymer composition damaged the mannan layer of the cell wall, with additional membrane-disrupting activity. The synergistic combination of the polymer with caspofungin prevented infection of human epithelial cells in vitro, improved fungal clearance by human macrophages, and significantly increased host survival in a Galleria mellonella model of systemic candidiasis. Additionally, prolonged exposure of C. albicans to the synergistic combination of polymer and caspofungin did not lead to the evolution of tolerant strains in vitro. Together, this work highlights the enormous potential of these synthetic peptide mimics to be used as novel antifungal formulations as well as adjunctive antifungal therapy. Fungal infections are severely underestimated as a cause of mortality, and alternative drugs are urgently needed. Here, Schaefer et al. show that a synthetic polymer mimicking defensins shows different, but synergistic activity with known antifungals. [ABSTRACT FROM AUTHOR]

Introduction: For people with type 2 diabetes and/or cardiovascular conditions, deprescribing of glucose-lowering, blood pressure-lowering and/or lipid-lowering medication is recommended when they age, and their health status deteriorates. So far, deprescribing rates of these so-called cardiometabolic medications are low. A review of challenges and interventions addressing these challenges in this population is pertinent. Areas covered: We first provide an overview of relevant deprescribing recommendations. Next, we review challenges for healthcare providers (HCPs) to deprescribe cardiometabolic medication and provide insight in the patient and caregiver perspective on deprescribing. We summarize findings from research on implementing deprescribing of cardiometabolic medication and reflect on strategies to enhance deprescribing. We have used a combination of methods to search for relevant articles. Expert opinion: There is a need for rigorous development and evaluation of intervention strategies aimed at proactive deprescribing of cardiometabolic medication. To address challenges at different levels, these should be multifaceted interventions. All stakeholders must become aware of the relevance of deintensifying medication in this population. Education and training for HCPs and patients should support patient-centered communication and shared decision-making. Development of procedures and tools to select eligible patients and conduct targeted medication reviews are important for implementation of deprescribing in routine care. [ABSTRACT FROM AUTHOR]

Background: Health policy promotes patient participation in decision making about service organisation. In English general practice this happens through contractually required patient participation groups (PPGs). However, there are problems with the enactment of PPGs that have not been systematically addressed. Aim: To observe how a co-designed theory-informed intervention can increase representational legitimacy and facilitate power sharing to support PPGs to influence decision making about general practice service improvement. Design and setting: Participatory action research to implement the intervention in two general practices in the North of England was undertaken. The intervention combined two different participatory practices: partnership working involving externally facilitated meetings with PPG members and staff; and consultation with the wider patient population using a bespoke discrete choice experiment (DCE). Method: To illustrate decision making in PPGs, qualitative data are presented from participant observation notes and photographed visual data generated through participatory methods. The DCE results are summarised to illustrate how wider population priorities contributed to overall decision making. Observational data were thematically analysed using normalisation process theory with support from a multi-stakeholder co-research group. Results: In both general practices, patients influenced decision making during PPG meetings and through the DCE, resulting in bespoke patient-centred action plans for service improvement. Power asymmetries were addressed through participatory methods, clarification of PPG roles in decision making, and addressing representational legitimacy through wider survey consultation. Conclusion: Combining participatory practices and facilitated participatory methods enabled patients to influence decision making about general practice service improvement. The policy of mandatory PPGs needs updating to recognise the need to resource participation in a meaningful way. [ABSTRACT FROM AUTHOR]

Resistance to antibiotics is a critical growing public health problem that desires urgent action to combat. To avoid the stress on bacterial growth that evokes the resistance development, anti-virulence agents can be an attractive strategy as they do not target bacterial growth. Quorum sensing (QS) systems play main roles in controlling the production of diverse virulence factors and biofilm formation in bacteria. Thus, interfering with QS systems could result in mitigation of the bacterial virulence. Cilostazol is an antiplatelet and a vasodilator FDA approved drug. This study aimed to evaluate the anti-virulence activities of cilostazol in the light of its possible interference with QS systems in Pseudomonas aeruginosa. Additionally, the study examines cilostazol's impact on the bacterium's ability to induce infection in vivo, using sub-inhibitory concentrations to minimize the risk of resistance development. In this context, the biofilm formation, the production of virulence factors and influence on the in vivo ability to induce infection were assessed in the presence of cilostazol at sub-inhibitory concentration. Furthermore, the outcome of combination with antibiotics was evaluated. Cilostazol interfered with biofilm formation in P. aeruginosa. Moreover, swarming motility, biofilm formation and production of virulence factors were significantly diminished. Histopathological investigation revealed that liver, spleen and kidney tissues damage was abolished in mice injected with cilostazol-treated bacteria. Cilostazol exhibited a synergistic outcome when used in combination with antibiotics. At the molecular level, cilostazol downregulated the QS genes and showed considerable affinity to QS receptors. In conclusion, Cilostazol could be used as adjunct therapy with antibiotics for treating Pseudomonal infections. This research highlights cilostazol's potential to combat bacterial infections by targeting virulence mechanisms, reducing the risk of antibiotic resistance, and enhancing treatment efficacy against P. aeruginosa. These findings open avenues for repurposing existing drugs, offering new, safer, and more effective infection control strategies. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD), a prevalent and progressive degenerative disease of the macula, is the leading cause of blindness in elderly individuals in developed countries. The advanced stages include neovascular AMD (nAMD), characterized by choroidal neovascularization (CNV), leading to subretinal fibrosis and permanent vision loss. Despite the efficacy of anti-vascular endothelial growth factor (VEGF) therapy in stabilizing or improving vision in nAMD, the development of subretinal fibrosis following CNV remains a significant concern. In this review, we explore multifaceted aspects of subretinal fibrosis in nAMD, focusing on its clinical manifestations, risk factors, and underlying pathophysiology. We also outline the potential sources of myofibroblast precursors and inflammatory mechanisms underlying their recruitment and transdifferentiation. Special attention is given to the potential role of mast cells in CNV and subretinal fibrosis, with a focus on putative mast cell mediators, tryptase and granzyme B. We summarize our findings on the role of GzmB in CNV and speculate how GzmB may be involved in the pathological transition from CNV to subretinal fibrosis in nAMD. Finally, we discuss the advantages and drawbacks of animal models of subretinal fibrosis and pinpoint potential therapeutic targets for subretinal fibrosis. [ABSTRACT FROM AUTHOR]