A molecular dynamics simulation study of glycine/serine octapeptides labeled with 2,3-diazabicyclo[2.2.2]oct-2-ene fluorophore.

The compound 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) is a versatile fluorophore widely used in Förster resonance energy transfer (FRET) spectroscopy studies due to its remarkable sensitivity, enabling precise donor-acceptor distance measurements, even for short peptides. Integrating time-resolved and FRET spectroscopies with molecular dynamics simulations provides a robust approach to unravel the structure and dynamics of biopolymers in a solution. This study investigates the structural behavior of three octapeptide variants: Trp-(Gly-Ser)3-Dbo, Trp-(GlyGly)3-Dbo, and Trp-(SerSer)3-Dbo, where Dbo represents the DBO-containing modified aspartic acid, using molecular dynamics simulations. Glycine- and serine-rich amino acid fragments, common in flexible protein regions, play essential roles in functional properties. Results show excellent agreement between end-to-end distances, orientational factors from simulations, and the available experimental and theoretical data, validating the reliability of the GROMOS force field model. The end-to-end distribution, modeled using three Gaussian distributions, reveals a complex shape, confirmed by cluster analysis highlighting a limited number of significant conformations dominating the peptide landscape. All peptides predominantly adopt a disordered state in the solvent, yet exhibit a compact shape, aligning with the model of disordered polypeptide chains in poor solvents. Conformations show marginal dependence on chain composition, with Ser-only chains exhibiting slightly more elongation. This study enhances our understanding of peptide behavior, providing valuable insights into their structural dynamics in solution.

Emulating biological synaptic characteristics of HfOx/AlN-based 3D vertical resistive memory for neuromorphic systems.

Here, we demonstrate double-layer 3D vertical resistive random-access memory with a hole-type structure embedding Pt/HfOx/AlN/TiN memory cells, conduct analog resistive switching, and examine the potential of memristors for use in neuromorphic systems. The electrical characteristics, including resistive switching, retention, and endurance, of each layer are also obtained. Additionally, we investigate various synaptic characteristics, such as spike-timing dependent plasticity, spike-amplitude dependent plasticity, spike-rate dependent plasticity, spike-duration dependent plasticity, and spike-number dependent plasticity. This synapse emulation holds great potential for neuromorphic computing applications. Furthermore, potentiation and depression are manifested through identical pulses based on DC resistive switching. The pattern recognition rates within the neural network are evaluated, and based on the conductance changing linearly with incremental pulses, we achieve a pattern recognition accuracy of over 95%. Finally, the device's stability and synapse characteristics exhibit excellent potential for use in neuromorphic systems.

Transferable non-invasive modal fusion-transformer (NIMFT) for end-to-end hand gesture recognition.

Objective.Recent studies have shown that integrating inertial measurement unit (IMU) signals with surface electromyographic (sEMG) can greatly improve hand gesture recognition (HGR) performance in applications such as prosthetic control and rehabilitation training. However, current deep learning models for multimodal HGR encounter difficulties in invasive modal fusion, complex feature extraction from heterogeneous signals, and limited inter-subject model generalization. To address these challenges, this study aims to develop an end-to-end and inter-subject transferable model that utilizes non-invasively fused sEMG and acceleration (ACC) data.Approach.The proposed non-invasive modal fusion-transformer (NIMFT) model utilizes 1D-convolutional neural networks-based patch embedding for local information extraction and employs a multi-head cross-attention (MCA) mechanism to non-invasively integrate sEMG and ACC signals, stabilizing the variability induced by sEMG. The proposed architecture undergoes detailed ablation studies after hyperparameter tuning. Transfer learning is employed by fine-tuning a pre-trained model on new subject and a comparative analysis is performed between the fine-tuning and subject-specific model. Additionally, the performance of NIMFT is compared to state-of-the-art fusion models.Main results.The NIMFT model achieved recognition accuracies of 93.91%, 91.02%, and 95.56% on the three action sets in the Ninapro DB2 dataset. The proposed embedding method and MCA outperformed the traditional invasive modal fusion transformer by 2.01% (embedding) and 1.23% (fusion), respectively. In comparison to subject-specific models, the fine-tuning model exhibited the highest average accuracy improvement of 2.26%, achieving a final accuracy of 96.13%. Moreover, the NIMFT model demonstrated superiority in terms of accuracy, recall, precision, and F1-score compared to the latest modal fusion models with similar model scale.Significance.The NIMFT is a novel end-to-end HGR model, utilizes a non-invasive MCA mechanism to integrate long-range intermodal information effectively. Compared to recent modal fusion models, it demonstrates superior performance in inter-subject experiments and offers higher training efficiency and accuracy levels through transfer learning than subject-specific approaches.

Predicting the responses of European grassland communities to climate and land cover change.

European grasslands are among the most species-rich ecosystems on small spatial scales. However, human-induced activities like land use and climate change pose significant threats to this diversity. To explore how climate and land cover change will affect biodiversity and community composition in grassland ecosystems, we conducted joint species distribution models (SDMs) on the extensive vegetation-plot database sPlotOpen to project distributions of 1178 grassland species across Europe under current conditions and three future scenarios. We further compared model accuracy and computational efficiency between joint SDMs (JSDMs) and stacked SDMs, especially for rare species. Our results show that: (i) grassland communities in the mountain ranges are expected to suffer high rates of species loss, while those in western, northern and eastern Europe will experience substantial turnover; (ii) scaling anomalies were observed in the predicted species richness, reflecting regional differences in the dominant drivers of assembly processes; (iii) JSDMs did not outperform stacked SDMs in predictive power but demonstrated superior efficiency in model fitting and predicting; and (iv) incorporating co-occurrence datasets improved the model performance in predicting the distribution of rare species. This article is part of the theme issue 'Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere'.

Association of cardiovascular disease prevalence with BMD and fracture in men with T2DM.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are predisposed to cardiovascular disease (CVD). Bone mineral density (BMD) is linked to CVD, but most studies focused on women. Our analysis aims to explore the association of BMD and fracture with the prevalence of CVD in men with T2DM. METHODS: In this retrospective cross-sectional study, 856 men with T2DM were enrolled. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The CVD outcome was determined as the sum of the following conditions: congestive heart failure, coronary heart disease, angina pectoris, myocardial infarction, the requirement for coronary artery revascularization, and stroke. The relationship between BMDs and CVD was investigated by restricted cubic spline curves and logistic regression models. RESULTS: A total of 163 (19.0%) patients developed CVD. The restricted cubic spline curve revealed a linear and negative association between FN-BMD, TH-BMD, and CVD. After full adjustments for confounding covariates, the odds ratios were 1.34 (95% confidence interval [CI] [1.11-1.61], p < .05), 1.3 (95% CI [1.05-1.60], p < .05), and 1.26 (95% CI [1.02-1.55], p < .05) for each 1-SD decrease in BMDs of L2-4, FN and TH, respectively. T-scores of < -1 for BMD of L2-4 and FN were independently associated with CVD (p < .05). Subgroup analyses further supported our findings. CONCLUSIONS: The prevalence of CVD was inversely correlated with BMD levels in men with T2DM, particularly at the FN. We hypothesized that monitoring FN-BMD and early intervention would help reduce CVD risk in men with T2DM, especially those with hypertension.

The role of traditional Chinese medicine in postoperative wound complications of gastric cancer.

Due to the high risks of postoperative complications brought on by gastric cancer, traditional Chinese medicine (TCM) as a commonly used therapy, has exerted its vital role in postoperative recovery care. In this sense, this meta-analysis was conducted to explore the related documents about TCM's impact on gastric cancer postoperative recovery. During the research, we explored a total of 1549 results from databases PubMed, China National Knowledge Infrastructure (CNKI), Embase, Cochrane Library and Web of Science (WoS). Thirty-two clinical randomized trials (RCTs) were then selected and analysed for this meta-analysis by using the software RevMan 5.4 (under PRISMA 2020 regulations), with a population of 3178 patients. Data prove that TCM therapy reduced the risks for postoperative complications exposure by an estimated average of 19% (95% CI). Among the complications, TCM therapy suppressed the risks of wound infection and incisional infections by 53% and 48% respectively. Meanwhile, the patient's wound healing duration exhibited a significant reduction compared to those without TCM treatment, with a difference at around 0.74 days (95% CI). TCM also exerted its potential to strengthen the patient's immune and health conditions, leading to a significantly promoted gastrointestinal function in the patients with a shorter duration to release first exhaustion and defecation compared to those with no TCM therapy. In addition, similar promoted phenomena also exist in those patients with TCM therapy in terms of their immunity and nutritional conditions. These facts all indicate a positive impact of TCM therapy in clinical applications.

Glucose regulation of adipose tissue browning by CBP/p300- and HDAC3-mediated reversible acetylation of CREBZF.

Glucose is required for generating heat during cold-induced nonshivering thermogenesis in adipose tissue, but the regulatory mechanism is largely unknown. CREBZF has emerged as a critical mechanism for metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). We investigated the roles of CREBZF in the control of thermogenesis and energy metabolism. Glucose induces CREBZF in human white adipose tissue (WAT) and inguinal WAT (iWAT) in mice. Lys208 acetylation modulated by transacetylase CREB-binding protein/p300 and deacetylase HDAC3 is required for glucose-induced reduction of proteasomal degradation and augmentation of protein stability of CREBZF. Glucose induces rectal temperature and thermogenesis in white adipose of control mice, which is further potentiated in adipose-specific CREBZF knockout (CREBZF FKO) mice. During cold exposure, CREBZF FKO mice display enhanced thermogenic gene expression, browning of iWAT, and adaptive thermogenesis. CREBZF associates with PGC-1α to repress thermogenic gene expression. Expression levels of CREBZF are negatively correlated with UCP1 in human adipose tissues and increased in WAT of obese ob/ob mice, which may underscore the potential role of CREBZF in the development of compromised thermogenic capability under hyperglycemic conditions. Our results reveal an important mechanism of glucose sensing and thermogenic inactivation through reversible acetylation.

Synthesis and study of optical properties of a Gd3+-doped NaYF4 phosphor for phototherapy lamp application.

In recent trends, radiation falls under the narrowband ultraviolet-B region (305-315 nm) widely used in phototherapy lamp applications in the treatment of skin diseases. In this paper, we report a Gd3+-doped NaYF4 luminescent material synthesized for the first time using the low-temperature co-precipitation method. It crystallized into a face-centred cubic structure, as confirmed by X-ray diffraction characterization techniques and Rietveld refinement. The photoluminescence property of the as-prepared sample shows a highly intense, sharp emission band obtained at 311 nm, which belongs to the narrowband ultraviolet-B region and corresponds to the transition of the 6P7/2→8S7/2 level of the Gd3+ ions under 272 nm excitation (8S7/2 to 6IJ). The transitions of the Gd3+ ions are detected entirely with different concentrations of Gd3+ ions. Scanning electron microscopy analysis indicated that the average particle was 288 nm. The critical distance for energy transfer was calculated to be equal to 11.5017 Å. Dipole-dipole interaction is responsible for energy transfer, as analyzed by Dexter theory. These excellent optical characteristics, together with their highly efficient and low-cost synthesis approach, indicate that synthesized NaYF4:Gd3+ phosphors have excessive potential for phototherapeutic lamp applications.

Ultra Processed Foods: A South Asian culinary perspective.

There is a vast multitude of foodstuffs available, and health care professionals find it challenging to distinguish between healthy and unhealthy offerings. Recent evidence suggests that ultra processed foods should be avoided, as they are associated with harmful effects on health. This communication defines and describes ultra-processed foods, using the internationally accepted NOVA classification. It uses South Asian examples to make the concept easy to understand for South Asian readers.

Effects of duty cycle on passive acoustic monitoring metrics: The case of blue whale songs.

Long-term fixed passive acoustic monitoring of cetacean populations is a logistical and technological challenge, often limited by the battery capacity of the autonomous recorders. Depending on the research scope and target species, temporal subsampling of the data may become necessary to extend the deployment period. This study explores the effects of different duty cycles on metrics that describe patterns of seasonal presence, call type richness richness, and daily call rate of three blue whale acoustics populations in the Southern Indian Ocean. Detections of blue whale calls from continuous acoustic data were subsampled with three different duty cycles of 50%, 33%, and 25% within listening periods ranging from 1 min to 6 h. Results show that reducing the percentage of recording time reduces the accuracy of the observed seasonal patterns as well as the estimation of daily call rate and call call type richness. For a specific duty cycle, short listening periods (5-30 min) are preferred to longer listening periods (1-6 h). The effects of subsampling are greater the lower the species' vocal activity or the shorter their periods of presence. These results emphasize the importance of selecting a subsampling scheme adapted to the target species.

FLIM-FRET Protein-Protein Interaction Assay.

Fluorescence lifetime imaging performed under FRET conditions between two interacting molecules is a sensitive and robust way to quantify intermolecular interactions in cells. The fluorescence lifetime, an inherent property of the fluorophore, remains unaffected by factors such as concentration, laser intensity, and other photophysical artifacts. In the context of FLIM-FRET, the focus lies on measuring the fluorescence lifetime of the donor molecule, which diminishes upon interaction with a neighboring acceptor molecule. In this study, we present a step-by-step experimental protocol for applying FLIM-FRET to investigate protein-protein interactions involving various RAS isoforms and RAS effectors at the live cell's plasma membrane. By utilizing the FRET pair comprising enhanced green fluorescent protein (eGFP) and fluorescent mCherry, we demonstrate that the proximity and possible nanoclustering of eGFP-tagged KRAS4b G12D and mCherry-tagged KRAS4b WT led to a reduction in the donor eGFP's fluorescence lifetime. The donor lifetime of eGFP-tagged KRAS decreases even further when treated with a dimer-inducing small molecule, or in the presence of RAF proteins, suggesting a greater FRET efficiency, and thus less distance, between donor and acceptor.

Studying RAS Interactions in Live Cells with BRET.

Bioluminescence resonance energy transfer (BRET) is a valuable technique for studying protein-protein interactions (PPIs) within live cells (Pfleger and Eidne, Nat Methods 3:165-174, 2006). Among the various BRET methodologies, a recent addition called NanoBRET has emerged, leveraging advancements in donor and acceptor technologies (Machleidt and Woodroofe, ACS Chem Biol 10:1797-1804, 2015). In this study, we present a developed methodology designed to measure PPIs involving the RAS protein family and their effectors and interactors at the plasma membrane. By utilizing the NanoLuc and HaloTag BRET pair, we provide evidence of a saturable interaction between KRAS4b-G12D and full-length RAF1. Conversely, the RAF1 R89L mutant, known to impede RAF1 binding to active RAS, exhibits nonspecific interactions. The assay exhibits remarkable signal-to-background ratios and is highly suitable for investigating the interactions of RAS with effectors, as well as for high-throughput screening assays.

KRAS4b:RAF-1 Homogenous Time-Resolved Fluorescence Resonance Energy Transfer Assay for Drug Discovery.

Homogenous time-resolved FRET (HTRF) assays have become one of the most popular tools for pharmaceutical drug screening efforts over the last two decades. Large Stokes shifts and long fluorescent lifetimes of lanthanide chelates lead to robust signal to noise, as well as decreased false positive rates compared to traditional assay techniques. In this chapter, we describe an HTRF protein-protein interaction (PPI) assay for the KRAS4b G-domain in the GppNHp-bound state and the RAF-1-RBD currently used for drug screens. Application of this assay contributes to the identification of lead compounds targeting the GTP-bound active state of K-RAS.

Analysing food groups and nutrient intake in adults who met and did not meet the daily recommended vegetable intake of 350 g: the 2016 National Health and Nutrition Survey in Japan.

This study aimed to compare the differences in the intake of food groups and nutrients between Japanese adults who consumed the recommended daily vegetable intake (350 g/day) and those who did not. Dietary information was obtained from one-day dietary records collected from the 2016 National Health and Nutrition Survey, which was conducted in 46 prefectures in Japan. The participants aged ≥20 years (n = 21,606; 53.8% women) were classified into the < and ≥350 g/day groups. Inter-group differences for 17 food groups and 27 nutrients were assessed as percentages of consumers (food groups only) and energy-adjusted intake (units/MJ/d or % of total energy intake). Overall, 29% of participants consumed ≥350 g/day of vegetables. The ≥350 g/day group had a higher percentage of consumers and energy-adjusted intakes for all vegetable subgroups than the <350 g/day group. For other food groups, the ≥350 g/day group had higher percentages of consumers for all food groups, except for cereals, eggs, and condiments and seasonings, which showed no significant differences. However, the ≥350 g/day group had a significantly higher energy-adjusted intake for potatoes and other tubers, mushrooms, meats, and condiments and seasonings but a significantly lower value for cereals, eggs, savoury snacks and confectionaries, and beverages. The ≥350 g/day group had a significantly higher intake of almost all (25/27) nutrients, including sodium, than the <350 g/day group. Participants with vegetable intake ≥350 g/day might have a more favourable intake of food groups and nutrients; however, watching for salt intake is necessary when promoting vegetable intake.

[Care assistants at the international level: a narrative review]. / Gli operatori di supporto a livello internazionale: una revisione narrativa.

. Care assistants at the international level: a narrative review. INTRODUCTION: At the international level, the role of care assistants, their competencies and scope of their professional practice has been debated for many years. Periodically updating the state of the art regarding the different training pathways, expected competencies, and responsibilities of care assistants at the international level is crucial for monitoring the evolution of these professional profiles. OBJECTIVE: To map the available classifications of care assistants at the international level, by describing (a) where these figures receive training, with which pathways, and for which competencies, and (b) where they can work and with what level of professional autonomy/interdependence with respect to other healthcare professions. METHOD: A narrative review of the literature was conducted by examining documents produced by the World Health Organization and the European Union; and that of three reference countries, the United Kingdom, Canada, and the United States of America. RESULTS: Fourteen documents were selected. Numerous care assistant profiles are described in available classifications, totaling 32 different profiles; these individuals may receive training in upper secondary school or colleges to perform a range of competencies. They may be supervised in their practice not only by nurses. In some countries, compulsory registration is required. DISCUSSION: The results show an important heterogeneity in care assistant figures internationally.

Navigating the Science System: Research Integrity and Academic Survival Strategies.

Research Integrity (RI) is high on the agenda of both institutions and science policy. The European Union as well as national ministries of science have launched ambitious initiatives to combat misconduct and breaches of research integrity. Often, such initiatives entail attempts to regulate scientific behavior through guidelines that institutions and academic communities can use to more easily identify and deal with cases of misconduct. Rather than framing misconduct as a result of an information deficit, we instead conceptualize Questionable Research Practices (QRPs) as attempts by researchers to reconcile epistemic and social forms of uncertainty in knowledge production. Drawing on previous literature, we define epistemic uncertainty as the inherent intellectual unpredictability of scientific inquiry, while social uncertainty arises from the human-made conditions for scientific work. Our core argument-developed on the basis of 30 focus group interviews with researchers across different fields and European countries-is that breaches of research integrity can be understood as attempts to loosen overly tight coupling between the two forms of uncertainty. Our analytical approach is not meant to relativize or excuse misconduct, but rather to offer a more fine-grained perspective on what exactly it is that researchers want to accomplish by engaging in it. Based on the analysis, we conclude by proposing some concrete ways in which institutions and academic communities could try to reconcile epistemic and social uncertainties on a more collective level, thereby reducing incentives for researchers to engage in misconduct.

Optimal sizing and power losses reduction of photovoltaic systems using PSO and LCL filters.

The integration of renewable energy systems into electricity grids is a solution for strengthening electricity distribution networks (SEDNs). Renewable energies such as solar photovoltaics are suitable for reinforcing a low-voltage line by offering an electrical energy storage system. However, the integration of photovoltaic systems can lead to problems of harmonic distortion due to the presence of direct current or non-linear feedback in networks from other sources. Therefore, connection standards exist to ensure the quality of the energy before injection at a point of common coupling (PCC). In this work, particle swarm optimization (PSO) is used to control a boost converter and to evaluate the power losses and the harmonic distortion rate. The test on the IEEE 14 bus standard makes it possible to determine the allocation or integration nodes for other sources such as biomass, wind or hydrogen generators, in order to limit the impact of harmonic disturbances (LIHs). The evaluation of the harmonic distortion rate, the power losses as well as the determination of the system size is done using an objective function defined based on the integration and optimization constraints of the system. The proposed model performs better since the grid current and voltage are stabilized in phase after the photovoltaic source is injected.

Public health relevance of medicines developed under paediatric legislation in Europe and the USA: a systematic mapping study.

BACKGROUND: Legislation in the European Union (EU) and the USA promoting the development of paediatric medicines has contributed to new treatments for children. This study explores how such legislation responds to paediatric health needs in different country settings and globally, and whether it should be considered for wider implementation. METHODS: We searched EU and US regulatory databases for medicines with approved indications resulting from completed paediatric development between 2007 and 2018. Of 195 medicines identified, 187 could be systematically mapped to the burden of the target disease for six study countries (Australia, Brazil, Canada, Kenya, Russia, South Africa) and globally, using disability-adjusted life years (DALYs). All medicines were also screened for inclusion on the WHO Model List of Essential Medicines (EML) and the EML for children under 13 years (EMLc). RESULTS: The studied medicines were disproportionately focused on non-communicable diseases, which represented 68% of medicines and 21% of global paediatric DALYs. On the other hand, we found 28% of medicines for communicable, maternal, neonatal and nutritional disorders, representing 73% of global paediatric DALYs. Neonatal disorders and malaria were mapped with two medicines, tuberculosis and neglected tropical diseases with none. The gap between medicines and paediatric DALYs was greater in countries with lower income. Still, 34% of medicines are included in the EMLc and 48% in the EML. CONCLUSIONS: Paediatric policies in the EU and the USA are only partially responsive to paediatric health needs. To be considered for wider implementation, paediatric incentives and obligations should be more targeted towards paediatric health needs. International harmonisation of legislation and alignment with global research priorities could further strengthen its impact on child health and support ongoing efforts to improve access to medicines. Furthermore, efforts should be made to ensure global access to authorised paediatric medicines.

Orthogonal analysis of mitochondrial function in Parkinson's disease patients.

The etiopathology of Parkinson's disease has been associated with mitochondrial defects at genetic, laboratory, epidemiological, and clinical levels. These converging lines of evidence suggest that mitochondrial defects are systemic and causative factors in the pathophysiology of PD, rather than being mere correlates. Understanding mitochondrial biology in PD at a granular level is therefore crucial from both basic science and translational perspectives. In a recent study, we investigated mitochondrial alterations in fibroblasts obtained from PD patients assessing mitochondrial function in relation to clinical measures. Our findings demonstrated that the magnitude of mitochondrial alterations parallels disease severity. In this study, we extend these investigations to blood cells and dopamine neurons derived from induced pluripotent stem cells reprogrammed from PD patients. To overcome the inherent metabolic heterogeneity of blood cells, we focused our analyses on metabolically homogeneous, accessible, and expandable erythroblasts. Our results confirm the presence of mitochondrial anomalies in erythroblasts and induced dopamine neurons. Consistent with our previous findings in fibroblasts, we observed that mitochondrial alterations are reversible, as evidenced by enhanced mitochondrial respiration when PD erythroblasts were cultured in a galactose medium that restricts glycolysis. This observation indicates that suppression of mitochondrial respiration may constitute a protective, adaptive response in PD pathogenesis. Notably, this effect was not observed in induced dopamine neurons, suggesting their distinct bioenergetic behavior. In summary, we provide additional evidence for the involvement of mitochondria in the disease process by demonstrating mitochondrial abnormalities in additional cell types relevant to PD. These findings contribute to our understanding of PD pathophysiology and may have implications for the development of novel biomarkers and therapeutic strategies.