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To identify a novel optimized strategy for preventing fraudulent substitutions of squid species and origins, forty European squids (Loligo vulgaris) and forty flying squids (Todarodes sagittatus) from the Mediterranean Sea and Atlantic Ocean were analyzed for δ 13 C, δ 15 N, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Yb, and Lu using isotope ratio mass spectrometry and inductively coupled plasma-mass spectrometry. While δ 13 C and δ 15 N variations were mainly species-related, they alone could not reliably distinguish samples. To address this issue, decision rules were developed using Classification and Regression Tree analysis. Threshold values for δ 13 C (-19.91‰), δ 15 N (14.87‰), and Pr (0.49 μg kg -1 ) enabled successful discrimination among Mediterranean European squids, Atlantic European squids, Mediterranean flying squids, and Atlantic flying squids, achieving over 90% accuracy, 81% precision, 80% sensitivity, and 93% specificity. This method holds promise for enhancing traceability and safety in the seafood industry, ensuring product integrity and consumer trust., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tumor cells often adapt to amino acid deprivation through metabolic rewiring, compensating for the loss with alternative amino acids/substrates. We have described such a scenario in leukemic cells treated with L-asparaginase (ASNase). Clinical effect of ASNase is based on nutrient stress achieved by its dual enzymatic action which leads to depletion of asparagine and glutamine and is accompanied with elevated aspartate and glutamate concentrations in serum of acute lymphoblastic leukemia patients. We showed that in these limited conditions glutamate uptake compensates for the loss of glutamine availability. Extracellular glutamate flux detection confirms its integration into the TCA cycle and its participation in nucleotide and glutathione synthesis. Importantly, it is glutamate-driven de novo synthesis of glutathione which is the essential metabolic pathway necessary for glutamate's pro-survival effect. In vivo findings support this effect by showing that inhibition of glutamate transporters enhances the therapeutic effect of ASNase. In summary, ASNase induces elevated extracellular glutamate levels under nutrient stress, which leads to a rewiring of intracellular glutamate metabolism and has a negative impact on ASNase treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for chronic kidney disease (CKD) evaluation and management bring important updates, particularly for European laboratories. These guidelines emphasize the need for harmonization in CKD testing, promoting the use of regional equations. In Europe, the European Kidney Function Consortium (EKFC) equation is particularly suited for European populations, particularly compared to the CKD-EPI 2021 race-free equation. A significant focus is placed on the combined use of creatinine and cystatin C to estimate glomerular filtration rate (eGFRcr-cys), improving diagnostic accuracy. In situations where eGFR may be inaccurate or clinically insufficient, the guidelines encourage the use of measured GFR (mGFR) through exogenous markers like iohexol. These guidelines emphasize the need to standardize creatinine and cystatin C measurements, ensure traceability to international reference materials, and adopt harmonized reporting practices. The recommendations also highlight the importance of incorporating risk prediction models, such as the Kidney Failure Risk Equation (KFRE), into routine clinical practice to better tailor patient care. This article provides a European perspective on how these KDIGO updates should be implemented in clinical laboratories to enhance CKD diagnosis and management, ensuring consistency across the continent., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background and Objectives: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS., Methods: In this retrospective study, we collected 3D T1-weighted brain MRI scans of PwMS to build (1) a cross-sectional multicentric cohort for age and disease duration (DD) modeling and (2) a longitudinal single-center cohort of patients with early MS as a clinical use case. We trained and evaluated a 3D DenseNet architecture to predict DD from minimally preprocessed images while age predictions were obtained with the DeepBrainNet model. The brain-predicted DD gap (the difference between predicted and actual duration) was proposed as a DD-adjusted global measure of MS-specific brain damage. Model predictions were scrutinized to assess the influence of lesions and brain volumes while the DD gap was biologically and clinically validated within a linear model framework assessing its relationship with BAG and physical disability measured with the Expanded Disability Status Scale (EDSS)., Results: We gathered MRI scans of 4,392 PwMS (69.7% female, age: 42.8 ± 10.6 years, DD: 11.4 ± 9.3 years) from 15 centers while the early MS cohort included 749 sessions from 252 patients (64.7% female, age: 34.5 ± 8.3 years, DD: 0.7 ± 1.2 years). Our model predicted DD better than chance (mean absolute error = 5.63 years, R 2 = 0.34) and was nearly orthogonal to the brain-age model (correlation between DD and BAGs: r = 0.06 [0.00-0.13], p = 0.07). Predictions were influenced by distributed variations in brain volume and, unlike brain-predicted age, were sensitive to MS lesions (difference between unfilled and filled scans: 0.55 years [0.51-0.59], p < 0.001). DD gap significantly explained EDSS changes ( B = 0.060 [0.038-0.082], p < 0.001), adding to BAG (Δ R 2 = 0.012, p < 0.001). Longitudinally, increasing DD gap was associated with greater annualized EDSS change ( r = 0.50 [0.39-0.60], p < 0.001), with an incremental contribution in explaining disability worsening compared with changes in BAG alone (Δ R 2 = 0.064, p < 0.001)., Discussion: The brain-predicted DD gap is sensitive to MS-related lesions and brain atrophy, adds to the brain-age paradigm in explaining physical disability both cross-sectionally and longitudinally, and may be used as an MS-specific biomarker of disease severity and progression.

Importance: Advancements in molecular engineering have facilitated the creation of engineered T cells that express synthetic receptors, termed chimeric antigen receptors (CARs). This is promising not only in cancer treatment but also in addressing a spectrum of other conditions. This review provides a comprehensive overview of the current approaches and future potential of CAR T-cell therapy in the field of neurology, particularly for primary brain tumors and autoimmune neurological disorders., Observations: CAR T-cell therapy for glioblastoma is promising; however, first-in-human trials did not yield significant success or showed only limited success in a subset of patients. To date, the efficacy of CAR T-cell therapies has been demonstrated in animal models of multiple sclerosis, but larger human studies to corroborate the efficacy remain pending. CAR T cells showed efficacy in treatment of patients with relapsed or refractory aquaporin 4-immunoglobulin G-seropositive neuromyelitis optica spectrum disorders. Further studies with larger patient populations are needed to confirm these results. Success was reported also for treatment of cases with generalized myasthenia gravis using CAR T cells. Chimeric autoantibody receptor T cells, representing a modified form of CAR T cells directed against autoreactive B cells secreting autoantibodies, were used to selectively target autoreactive anti-N-methyl-d-aspartate B cells under in vitro and in vivo conditions, providing the basis for human studies and application to other types of autoimmune encephalitis associated with neuronal or glial antibodies., Conclusions and Relevance: CAR T cells herald a new era in the therapeutic landscape of neurological disorders. While their application in solid tumors, such as glioblastoma, has not universally yielded robust success, emerging innovative strategies show promise, and there is optimism for their effectiveness in certain autoimmune neurological disorders.

Purpose of the Review: The purpose of this Review was to summarize the evidence on the associations among estrogen status, cellular senescence, the gut microbiome and osteoporosis., Recent Findings: Indicate that osteoporosis is a global public health problem that impacts individuals and society. In postmenopausal women, a decrease in estrogen levels is associated with a decrease in gut microbial diversity and richness, as well as increased permeability of the gut barrier, which allows for low-grade inflammation. The direct effects of estrogen status on the association between bone and the gut microbiome were observed in untreated and treated ovariectomized women. In addition to the direct effects of estrogens on bone remodeling, estrogen therapy could reduce the risk of postmenopausal osteoporosis by preventing increased gut epithelial permeability, bacterial translocation and inflammaging. However, in studies comparing the gut microbiota of older women, there were no changes at the phylum level, suggesting that age-related comorbidities may have a greater impact on changes in the gut microbiota than menopausal status does. Estrogens modify bone health not only by directly influencing bone remodeling, but also indirectly by influencing the gut microbiota, gut barrier function and the resulting changes in immune system reactivity., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests. Human and Animal Rights and Informed Consent: All the reported data from the human studies performed by the authors have been previously published and complied with all the applicable ethical standards including the Helsinki Declaration and its amendments institutional/national research committee standards and guidelines., (© 2024. The Author(s).)

The ongoing energy crisis has made it imperative to develop low-cost, easily fabricated, yet efficient materials. It is highly desirable for these nanomaterials to function effectively in multiple applications. Among transition metal dichalcogenides, tungsten diselenide (WSe 2 ) shows great promise but remains understudied. In this work, we doped WSe 2 with Mn using a simple hydrothermal method. The resulting material exhibited excellent electrocatalytic activity for the hydrogen evolution reaction, achieving a low overpotential of -0.28 V vs. RHE at -10 mA cm -2 , enhanced conductivity, and high stability and durability. Moreover, as an anode material in lithium-ion batteries, the Mn-doped WSe 2 outperformed pristine WSe 2 , reaching initial discharge capacities of 1223 and 922 mA h g -1 , respectively. Additionally, the Mn-doped material maintained a significantly higher discharge capacity of 201 mA h g -1 compared to intact WSe 2 , which had 68 mA h g -1 after 150 cycles. This work offers novel insights into designing efficient bifunctional nanomaterials using transition metal dichalcogenides.

Exposure to aromatic amines may occur via tobacco smoke, hair dyes or tattoo inks, but also in the workplace during certain manufacturing processes. As some aromatic amines are known or suspected carcinogens, human biomonitoring (HBM) is essential to assess their exposure. Aromatic amines were among the selected chemicals in HBM4EU, a European-wide project to harmonise and advance HBM within 30 European countries. For this purpose, the analytical comparability and accuracy of participating laboratories were assessed by a QA/QC programme comprising interlaboratory comparison investigations (ICIs) and external quality assurance schemes (EQUASs). This paper presents the evaluation process and discusses the results of three ICI/EQUAS rounds for the determination of aromatic amines in urine conducted in 2019 and 2020. The final evaluation included ten participants which analysed the following six targeted aromatic amines over three rounds: aniline, ortho -toluidine (TOL), 4,4'-methylenedianiline (MDA), 4,4'-methylenebis(2-chloroaniline) (MOCA), 2,4-diaminotoluene (2,4-TDA), and 2,6-diaminotoluene (2,6-TDA). Most participants achieved satisfactory and highly comparable results, although low quantification limits were required to quantify the parameters at the level of exposure in the general population. Hydrolysis of the sample followed by liquid-liquid extraction and subsequent analysis of the derivatised analytes by means of GC-MS/MS were preferred for the sensitive and precise determination of aromatic amines in urine. This QA/QC programme succeeded in establishing a network of laboratories with high analytical comparability and accuracy for the analysis of aromatic amines in Europe.

Aim: To assess the feasibility, safety and efficacy of using a high-flow nasal cannula (HFNC) for stabilising very preterm infants after birth., Methods: A prospective observational study included preterm infants born at 28 + 0 to 31 + 6 weeks' gestation between February 2021 and December 2022 at the General University Hospital in Prague. Following delayed cord clamping, HFNC was administered at a flow rate of 8 L/min through the infants' nostrils. Criteria for switching to continuous positive airway pressure (CPAP) or positive pressure ventilation (PPV) included persistent bradycardia in the first few minutes or low saturation of oxygen (SpO 2 ) after 5 min, respectively., Results: Of the 65 infants enrolled in the study, 56 (86%) were successfully stabilised exclusively using HFNC while 7 (11%) required PPV. Additionally, 52 (80%) infants achieved SpO 2 > 80% at 5 min, and 54 (83%) infants were successfully treated with HFNC within the first 3 h of life., Conclusion: The primary use of HFNC seems to be an appropriate alternative to CPAP for the stabilisation of very premature infants after birth and subsequent transfer to the NICU. A randomised trial comparing HFNC and CPAP in the delivery room will enable to answer the questions raised in this study., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

This study aimed to reveal interactions of the stress response sigma subunits (factors) σ D and σ H of RNA polymerase and promoters in Gram-positive bacterium Corynebacterium glutamicum by combining wet-lab obtained data and in silico modeling. Computer modeling-guided point mutagenesis of C. glutamicum σ H subunit led to the creation of a panel of σ H variants. Their ability to initiate transcription from naturally occurring hybrid σ D /σ H -dependent promoter Pcg0441 and two control canonical promoters (σ D -dependent PrsdA and σ H -dependent PuvrD3) was measured and interpreted using molecular dynamics simulations of homology models of all complexes. The results led us to design the artificial hybrid promoter PD 35 H 10 combining the -10 element of the PuvrD3 promoter and the -35 element of the PrsdA promoter. This artificial hybrid promoter PD 35-rsdA H 10-uvrD3 showed almost optimal properties needed for the bio-orthogonal transcription (not interfering with the native biological processes)., Competing Interests: Declarations. Conflict of interests: The authors declare that this work was carried out in the absence of any personal, professional, or financial relationships that could potentially be construed as a conflict of interest. Data Availability: No datasets were generated or analysed during the current study., (© 2024. The Author(s).)

The presented guidelines are an update of the position paper, endorsed by the International Osteoporosis Foundation (IOF), on nomenclature of bone markers published over 2 decades ago. Novel insight into bone biology and pathophysiology of bone disorders has highlighted the increasing relevance of new and known mediators implicated in various aspects of bone metabolism. This updated guideline proposes the nomenclature Bone Status Indices (BSI) as the comprehensive classification rather than bone turnover markers, bone markers, metabolic markers of bone turnover or metabolic markers of bone turnover, that are currently in use for the implicated molecules. On behalf of the IFCC Committee on Bone Metabolism and the Joint IOF Working Group and IFCC Committee on Bone Metabolism, the authors propose standardized nomenclature, abbreviations and measurement units for the bone status indices., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: To prospectively validate the diagnostic performance of a non-invasive point-of-care tool (Rapid IAI System), including vaginal alpha-fetoprotein and interleukin-6, to predict the occurrence of intra-amniotic inflammation in a Spanish cohort of patients admitted with a diagnosis of preterm labor and intact membranes., Methods: From 2017 to 2022, we prospectively evaluated a cohort of pregnant women diagnosed with preterm labor and intact membranes admitted below 34+0 weeks who underwent amniocentesis to rule-in/out intra-amniotic infection and/or inflammation. Vaginal sampling was performed at the time of amniocentesis or within 24-48 h. Amniotic fluid IL-6, vaginal alpha-fetoprotein and vaginal IL-6 concentrations were measured using a point-of-care tool provided by Hologic Inc., "Rapid IAI System". We defined intra-amniotic inflammation when amniotic fluid IL-6 values were greater than 11.3 ng/mL. During recruitment, clinicians were blinded to the results of the point-of-care tool. The original prediction model proposed by Hologic Inc. to predict intra-amniotic inflammation was validated in this cohort of patients., Results: We included 151 patients diagnosed with preterm labor and intact membranes. Among these, 29 (19.2 %) had intra-amniotic inflammation. The algorithm including vaginal IL-6 and alpha-fetoprotein showed an area under curve to predict intra-amniotic inflammation of 80.3 % (±5.3 %) with a sensitivity of 72.4 %, specificity of 84.6 %, positive predictive valuve (PPV) of 52.5 %, negative predictive value (NPV) of 92.9 %, and a positive likelihood ratio (LR+) of 4.6 and negative likelihood ratio (LR-) of 0.33., Conclusions: External validation of a non-invasive rapid point-of-care tool, including vaginal alpha-fetoprotein and IL-6, showed very good diagnostic performance for predicting the absence of intra-amniotic inflammation in women with preterm labor and intact membranes., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

The CACHE challenges are a series of prospective benchmarking exercises to evaluate progress in the field of computational hit-finding. Here we report the results of the inaugural CACHE challenge in which 23 computational teams each selected up to 100 commercially available compounds that they predicted would bind to the WDR domain of the Parkinson's disease target LRRK2, a domain with no known ligand and only an apo structure in the PDB. The lack of known binding data and presumably low druggability of the target is a challenge to computational hit finding methods. Of the 1955 molecules predicted by participants in Round 1 of the challenge, 73 were found to bind to LRRK2 in an SPR assay with a K D lower than 150 μM. These 73 molecules were advanced to the Round 2 hit expansion phase, where computational teams each selected up to 50 analogs. Binding was observed in two orthogonal assays for seven chemically diverse series, with affinities ranging from 18 to 140 μM. The seven successful computational workflows varied in their screening strategies and techniques. Three used molecular dynamics to produce a conformational ensemble of the targeted site, three included a fragment docking step, three implemented a generative design strategy and five used one or more deep learning steps. CACHE #1 reflects a highly exploratory phase in computational drug design where participants adopted strikingly diverging screening strategies. Machine learning-accelerated methods achieved similar results to brute force (e.g., exhaustive) docking. First-in-class, experimentally confirmed compounds were rare and weakly potent, indicating that recent advances are not sufficient to effectively address challenging targets.

Metal-free graphitic carbon nitrides are on the rise as polymer photocatalysts under visible light illumination, taking shares in a range of promising photocatalytic reactions, including water splitting. Their simple synthesis and facile structural modification afford them exceptional tunability, enabling the creation of photocatalysts with distinct properties. While their metal-free nature marks a significant step towards environmental sustainability, the high energy consumption required to produce carbon nitride photocatalysts remains a substantial barrier to their widespread adoption. Furthermore, the process of condensation at approximately 550 °C typically results in solid yields of less than 15 %, significantly challenging their economic viability. Here, we report on lowering manufacturing conditions of carbon nitride photocatalysts whilst enhancing photocatalytic activity by introducing binaphthyl diamine as a structural mediator. At 450 °C in 2 hours, carbon nitride photocatalyst shows a lower bandgap and enables visible light induced hydrogen evolution (194 μmol h -1 ) comparable to benchmark carbon nitride photocatalysts., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Perfusion dynamics play a vital role in delivering essential nutrients and oxygen to tissues while removing metabolic waste products. Imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) use contrast agents to visualize perfusion and clearance patterns; however, each technique has specific limitations. Hybrid PET/MRI combines the quantitative power and sensitivity of PET with the high functional and anatomical detail of MRI and holds great promise for precision in molecular imaging. However, the development of dual PET/MRI probes has been hampered by challenging synthesis and radiolabeling. Here, we present a novel PET/MRI probe, [ 18 F][Gd(FL 1 )], which exhibits excellent stability comparable to macrocyclic MRI contrast agents used in clinical practice. The unique molecular design of [ 18 F][Gd(FL 1 )] allows selective and expeditious radiolabeling of the gadolinium chelate in the final synthetic step. Leveraging the strengths of MRI and PET signals, the probe enables quantitative in vivo mapping of perfusion and excretion dynamics through an innovative voxel-based analysis. The diagnostic capabilities of [ 18 F][Gd(FL 1 )] were demonstrated in a pilot study on healthy mice, successfully detecting early cases of unilateral renal dysfunction, a condition that is typically challenging to diagnose. This study introduces a new approach for PET/MRI and emphasizes a streamlined probe design for practical synthesis and improved diagnostic accuracy., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Treatment of gingival fibroblasts with PDL extracellular vesicles results in promotion of Wnt signalling pathway and osteogenic differentiation. PDL secretome shows selective wound healing and matrix remodelling which can have implications for future periodontal regenerative strategies., (© 2024 The Author(s). Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Understanding mechanisms driving tropical tree growth is essential for comprehending carbon sequestration and predicting the future of tropical forests amid rapid deforestation. We conducted a natural experiment in Mount Cameroon to identify climatic factors limiting diurnal and seasonal growth in dominant tree species across a 2200-m elevation gradient, from lowland rainforests to montane mist forests with distinct wet and dry seasons. Using high-precision automatic dendrometers, we recorded radial growth rates of 28 tropical tree species from 2015 to 2018, correlating them with rainfall (11 100-2500 mm) and temperatures (23-14°C) across elevations. Significant growth limitations were suggested at both extremes of water availability. Tree growth peaked during the dry and prewet seasons at humid lower elevations and during wet seasons at drier higher elevations. Growth rates increased with soil moisture at higher elevations and peaked at medium soil moisture at lower elevations. Trees grew fastest at lower temperatures relative to their elevation-specific means, with growth limited by high daytime temperatures and promoted by nighttime temperatures. Our results revealed significant interspecific diurnal and seasonal growth variations hindered by both water scarcity and excess in West African rainforests, essential for forecasting and modelling carbon sinks., (© 2024 The Author(s). Plant, Cell & Environment published by John Wiley & Sons Ltd.)

Key Message: Anaesthetics affect not only humans and animals but also plants. Plants exposed to certain anaesthetics lose their ability to respond adequately to various stimuli such as touch, injury or light. Available results indicate that anaesthetics modulate ion channel activities in plants, e.g. Ca 2+ influx. The word anaesthesia means loss of sensation. Plants, as all living creatures, can also sense their environment and they are susceptible to anaesthesia. Although some anaesthetics are often known as drugs with well-defined target to their animal/human receptors, some other are promiscuous in their binding. Both have effects on plants. Application of general volatile anaesthetics (GVAs) inhibits plant responses to different stimuli but also induces strong cellular response. Of particular interest is the ability of GVAs inhibit long-distance electrical and Ca 2+ signalling probably through inhibition of GLUTAMATE RECEPTOR-LIKE proteins (GLRs), the effect which is surprisingly very similar to inhibition of nerve impulse transmission in animals or human. However, GVAs act also as a stressor for plants and can induce their own Ca 2+ signature, which strongly reprograms gene expression . Down-regulation of genes encoding enzymes of chlorophyll biosynthesis and pigment-protein complexes are responsible for inhibited de-etiolation and photomorphogenesis. Vesicle trafficking, germination, and circumnutation movement of climbing plants are also strongly inhibited. On the other hand, other cellular processes can be upregulated, for example, heat shock response and generation of reactive oxygen species (ROS). Upregulation of stress response by GVAs results in preconditioning/priming and can be helpful to withstand abiotic stresses in plants. Thus, anaesthetic drugs may become a useful tool for scientists studying plant responses to environmental stimuli., Competing Interests: Declarations. Conflict of interest: The author declares that he has no conflict of interest., (© 2024. The Author(s).)

Neuropsychiatric symptoms (NPS) are common in hereditary ataxias as a part of the cerebellar cognitive affective syndrome. In Friedreich ataxia (FRDA), one of the most common hereditary ataxias, depressive symptoms were previously reported, but little is known about other NPS. We aimed to study the presence and severity of a broad range of NPS in individuals with FRDA and assess the relationship between the NPS and the disease severity, cognition, and quality of life and to examine the concordance between the NPS reported by the patients and by their informants. Mild Behavioral Impairment Checklist (MBI-C), a questionnaire designed for screening NPS in the early stages of neurodegenerative diseases, was administered to informants of individuals with FRDA and healthy controls and to people with FRDA themselves. Compared to healthy controls, patients with FRDA scored significantly higher in the total MBI-C score, emotion dysregulation domain (corresponding to depression and anxiety), and decreased motivation domain. When assessed by caregiver, the total MBI-C score and several NPS domains correlated with activities of daily living. Only psychotic symptoms were related to ataxia severity and general cognition. When endorsed by patients, only the relation between few MBI-C domains and quality of life was observed. We found slight to moderate agreement between informant-rated and patient-rated scores. NPS, particularly emotion dysregulation and decreased motivation, are common and clinically relevant in FRDA and should receive more attention due to their potential impact on quality of life and the possibility of therapeutic intervention., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Studies have correlated living close to major roads with Alzheimer's disease (AD) risk. However, the mechanisms responsible for this link remain unclear., Methods: We exposed olfactory mucosa (OM) cells of healthy individuals and AD patients to diesel emissions (DE). Cytotoxicity of exposure was assessed, mRNA, miRNA expression, and DNA methylation analyses were performed. The discovered altered pathways were validated using data from the human population-based Rotterdam Study., Results: DE exposure resulted in an almost four-fold higher response in AD OM cells, indicating increased susceptibility to DE effects. Methylation analysis detected different DNA methylation patterns, revealing new exposure targets. Findings were validated by analyzing data from the Rotterdam Study cohort and demonstrated a key role of nuclear factor erythroid 2-related factor 2 signaling in responses to air pollutants., Discussion: This study identifies air pollution exposure biomarkers and pinpoints key pathways activated by exposure. The data suggest that AD individuals may face heightened risks due to impaired cellular defenses., Highlights: Healthy and AD olfactory cells respond differently to DE exposure. AD cells are highly susceptible to DE exposure. The NRF2 oxidative stress response is highly activated upon air pollution exposure. DE-exposed AD cells activate the unfolded protein response pathway. Key findings are also confirmed in a population-based study., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Most polyurethanes (PU) are currently produced through the polyaddition reaction of polyisocyanates with polyols and chain extenders, using components of petrochemical origin. From an environmental and geopolitical point of view, and with regard to the problems of oil supply and processing, the replacement of petrochemical PU raw materials with renewable resources is highly desirable. It is also one of the principles of sustainable development and an important challenge for chemical companies and market competitiveness. Current research studies focus mainly on the use of bio-based polyols for PUs, while other PU components, in particular polyisocyanates, remain of petrochemical origin. In this work, a series of PUs have been synthesized by polyaddition reactions of different types of renewable polyols and bio-based polyisocyanates. The effects of the bio-derived components on the structure, thermal stability and phase transformations of the PU were studied using FTIR and NMR spectroscopy, SWAXS, TGA, DSC, DMTA and TGA-FTIR. A full conversion of the bio-based monomers was achieved in all cases, indicating good compatibility and reactivity of all bio-based components. It was observed that bio-based PU exhibited a lower degree of phase separation and slightly lower thermal stability compared to PUs from petrochemical monomers., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The spread of tau pathology closely correlates with the disease course and cognitive decline in Alzheimer's disease (AD). Tau-targeting immunotherapies are being developed to stop the spread of tau pathology and thus halt disease progression. In this post hoc analysis of the ADAMANT clinical trial, we examined the performance of AADvac1, an active immunotherapy targeting the microtubule-binding region (MTBR) of tau, in a subgroup of participants with elevated plasma p-tau217, indicating AD-related neuropathological changes., Methods: ADAMANT was a 24-month, randomized, placebo-controlled, parallel-group, double-blinded, multicenter, phase 2 clinical trial in subjects with mild AD. The trial participants were randomized 3:2 to receive six doses of AADvac1 or placebo at 4-week intervals, followed by five booster doses at 14-week intervals. The primary outcome was safety. The secondary outcomes were the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Alzheimer's Disease Cooperative Study - Activities of Daily Living score for Mild Cognitive Impairment 18-item version (ADCS-ADL-MCI-18), and immunogenicity. Volumetric MRI, plasma neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were exploratory outcomes. The inclusion criterion for this post-hoc analysis was a baseline plasma p-tau217 level above the cutoff for AD., Results: Among 196 ADAMANT participants, 137 were positive for plasma p-tau217 (mean age 71.4 years, 59% women). AADvac1 was safe and well tolerated in this subgroup. AADvac1 reduced the rate of accumulation of log-plasma NfL by 56% and that of GFAP by 73%. The treatment differences in the CDR-SB and ADCS-ADL-MCI-18 scores favored AADvac1 but were not statistically significant. AADvac1 had no effect on whole-brain volume but nonsignificantly reduced the loss of brain cortical tissue in several regions. Importantly, the impact on the study outcomes was more pronounced in participants with higher anti-tau antibody levels., Conclusions: These results suggest that AADvac1 tau immunotherapy can reduce plasma biomarkers of neurodegeneration and neuroinflammation. These findings and possible observations on brain atrophy and cognition are hypothesis-generating and warrant further evaluation in a larger clinical trial., Trial Registration: EudraCT 2015-000630-30 (primary) and NCT02579252., Competing Interests: Declarations. Ethics approval and consent to participate: The ADAMANT study protocol (provided with the Statistical Analysis Plan in Clinical Trial Material Supplement) was approved by the appropriate ethics committees and competent authorities [8]. All patients and their caregivers provided written informed consent before the study procedures. Consent for publication: Not applicable. Competing interests: All authors affiliated with AXON Neuroscience SE or AXON Neuroscience R&D Services SE received salaries from their respective companies. Petr Novak received payments from F. Hoffmann-La Roche AG. The investigators’ institutions received reimbursement on a per-patient per-visit basis. Bengt Winblad received personal fees from Axon Neuroscience for participating in SAB and DSMB. Howard H Feldman reports serving as a consultant to AXON Neuroscience through a service agreement with UC San Diego. No funds have been personally received, and no funding for this manuscript has been received. All the authors affiliated with ADx NeuroSciences received a salary. Eugeen Vanmechelen is a cofounder of the company., (© 2024. The Author(s).)

Background: Skeletal muscle alterations are associated with higher mortality and morbidity in patients with liver cirrhosis. Assessing these changes seems to be a promising method for identifying patients at a high risk of poor outcomes following liver transplantation (LT). This is particularly important given the current global shortage of organ donors. However, evidence of the impact of these alterations on the prognosis of patients undergoing LT is inconclusive. The aim of our prospective study was to evaluate the impact of skeletal muscle changes, reflected in sarcopenia, myosteatosis and metabolic changes in the calf muscles, on perioperative outcomes and long-term survival after LT. We also sought to determine the posttransplant evolution of the resting muscle metabolism., Methods: We examined 134 adult LT candidates. Of these, 105 underwent LT. Sarcopenia and myosteatosis were diagnosed by measuring the skeletal muscle index and mean psoas muscle radiation attenuation, respectively, which were obtained from computed tomography (CT) scans taken during pretransplant assessment. Additionally, patients underwent 31 P MR spectroscopy (MRS) of the calf muscles at rest before LT and 6, 12 and 24 months thereafter. The median follow-up was 6 years., Results: Patients with abnormal 31 P MRS results and CT-diagnosed myosteatosis prior to LT had significantly worse long-term survival after LT (hazard ratio (HR), 3.36; 95% confidence interval (CI), 1.48-7.60; p = 0.0021 and HR, 2.58; 95% CI, 1.06-6.29; p = 0.03, respectively). Multivariable analysis showed that abnormal 31 P MR spectra (HR, 3.40; 95% CI, 1.50-7.71; p = 0.003) were a better predictor of worse long-term survival after LT than myosteatosis (HR, 2.78; 95% CI, 1.14-6.78; p = 0.025). Patients with abnormal 31 P MR spectra had higher blood loss during LT (p = 0.038), required a higher number of red blood cell transfusions (p = 0.006) and stayed longer in ICU (p = 0.041) and hospital (p = 0.007). Myosteatosis was associated with more revision surgeries following LT (p = 0.038) and a higher number of received red blood cell transfusion units (p = 0.002). Sarcopenia had no significant effect on posttransplant patient survival. An improvement in the resting metabolism of the calf muscles was observed at 12 and 24 months after LT., Conclusions: Abnormal 31 P MRS results of calf muscles were superior to CT-based diagnosis of myosteatosis and sarcopenia in predicting perioperative complications and long-term survival after LT. Resting muscle metabolism normalized 1 year after LT in most recipients., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Despite covering <5% of Earth's terrestrial area, peatlands are crucial for global carbon storage and are hot spots of methane cycling. This study examined the dynamics of aerobic and anaerobic methane oxidation in two undisturbed peatlands: a fen and a spruce swamp forest. Using microcosm incubations, we investigated the effect of ammonium addition, at a level similar to current N pollution processes, on aerobic methane oxidation. Our findings revealed higher methane consumption rates in fen compared to swamp peat, but no effect of ammonium amendment on methane consumption was found. Members of Methylocystis and Methylocella were the predominant methanotrophs in both peatlands. Furthermore, we explored the role of ferric iron and sulfate as electron acceptors for the anaerobic oxidation of methane (AOM). AOM occurred without the addition of an external electron acceptor in the fen, but not in the swamp peat. AOM was stimulated by sulfate and ferric iron addition in the swamp peat and inhibited by ferric iron in the fen. Our findings suggest that aerobic methane oxidizers are not N-limited in these peatlands and that there is an intrinsic potential for AOM in these environments, partially facilitated by ferric iron and sulfate acting as electron acceptors., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Tailocins are nano-scale phage tail-like protein complexes that can mediate antagonistic interactions between closely related bacterial species. While the capacity to produce R-type tailocin was found widely across Gammaproteobacteria, the production of F-type tailocins seems comparatively rare. In this study, we examined the freshwater isolate, Pragia fontium 24613, which can produce both R- and F-type tailocins. We investigated their inhibition spectrum, focusing on clinically relevant enterobacteria, and identified the associated tailocin gene cluster. Transmission electron microscopy confirmed that inactivation of the tape measure protein within the tailocin cluster disrupted R-tailocin production. Comparative analysis of Budviciaceae gene clusters showed high conservation of R-type tailocin genes, whereas F-type tailocin genes were found in only a few species, with little conservation. Our findings indicate a high prevalence of bacteriocin production among underexplored Enterobacteriales strains. Detected tailocins showed potential as antimicrobials targeting clinically significant pathogens., (Copyright © 2024. Published by Elsevier Masson SAS.)

This study investigated the impact of Hofstede cultural dimensions on sustainable competitive advantage with the mediating role of entrepreneurial innovativeness among Malays, Malaysian Chinese, and Malaysian Indian entrepreneurs in the retail industry. This study involved a quantitative approach with standardized questionnaires distributed among target respondents through non-probability sampling techniques, including snowball sampling, quota sampling, and convenience sampling. The data were collected in a cross-sectional setting from Malaysian retail ethnic entrepreneurs. AMOS-SEM and SPSS were used to analyze the data. The findings of this study revealed a positive and significant influence of indulgence, long-term orientation, masculinity, and low power distance on sustainable competitive advantage among Chinese, Malay, and Indian entrepreneurs. Furthermore, the direct effect of entrepreneurial innovativeness was also positive and significant in terms of sustainable competitive advantage among Chinese, Malay, and Indian entrepreneurs. Finally, the indirect effects of collectivism, indulgence, low uncertainty avoidance, low power distance, masculinity, and long-term orientation on sustainable competitive advantage through mediator entrepreneurial innovativeness were positive and significant among Malaysian Chinese. However, in Malay (indulgence) and India (collectivism, low uncertainty avoidance, and low power distance), these were not significant. Our results suggest that academics and businesses should consider how cultural norms of masculinity, long-term orientation, and uncertainty avoidance impact sustainable competitive advantage activities. Rewards encouraging sustainable competitive advantage in one subculture may not promote it in another. Subcultural norms influence entrepreneurs' decisions, expectations, and incentives in a culturally diverse community., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The Short Form-8 (SF-8) is a widely used 8-item tool for health-related quality of life assessment. This study aimed to evaluate the psychometric properties of the Slovak version of the SF-8 in a population sample., Methods: A cross-sectional survey on a Slovak representative sample (n = 1018; mean age 46.24 ± 16.56 years; 51.3% women) monitoring health and well-being was performed in 2019. Exploratory network analysis and confirmatory factor analysis were used to assess the construct validity of the scale. Reliability and sociodemographic differences were evaluated., Results: A 2-factor model had an adequate fit to the data [χ 2 (19) = 186.2, P < .001, comparative fit index = 0.998, Tucker-Lewis index = 0.997, root mean square error of approximation = 0.093, standardized root mean of residuals = 0.039], with high reliability (α = 0.93, ω = 0.95). The physical component score and mental component score (MCS) were negatively associated with the presence of chronic health conditions. Lower physical component score and MCS were associated with higher age (P < .001), and lower MCS were associated with female gender (P < .001)., Conclusions: The Slovak version of the SF-8 represents a valuable tool for measuring health-related quality of life in the Slovak population in both practice and research., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

The presented study focused on developing and optimizing a modern electroanalytical platform for the direct quantitative determination of galantamine. This work used different voltammetric methods to use a screen-printed sensor with a working boron-doped diamond electrode (SP/BDDE). Beneficial analytical performance for detecting galantamine was achieved in a Britton-Robinson buffer with pH 3.0. The oxidation peaks at 0.92 V and 1.20 V were followed for electrochemical quantification of galantamine. High-resolution mass spectrometry was used for the first time to analyze the products of preparative electrolysis, and a mechanism for the electrochemical oxidation of galantamine was proposed, which describes the demethylation of galantamine and the further oxidation of the hydroxyl group to a ketone group in the galantamine molecule. Coupled with the optimized parameters of differential pulse voltammetry and square-wave voltammetry on the SP/BDDE detected galantamine in two linear ranges (the first range was from 1.22 μM to 10 μM; the second range was from 10 μM to 200 μM), providing the limit of detection and limit of quantification on a micromolar level (0.50 μM and 1.48 μM, respectively). Amperometry and chronoamperometry were employed to develop a rapid detection method for galantamine. In this approach, galantamine can be detected at a level of 1.08 μM (amperometry at the second peak). The selectivity of the optimized amperometric methods was found to be excellent in the presence of ten times higher concentrations of certain interferences. The practical applicability of the SP/BDDE for detecting galantamine was demonstrated through the analysis of pharmaceutical products and human urine samples. The proposed procedure fully complies with the latest requirements of green analytical chemistry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The faster-X/Z effect hypothesis states that genes linked to X/Z chromosomes should accumulate mutations faster than autosomal genes. Although faster evolution of X/Z-linked genes has been reported in several plant and animal lineages, conflicting results have been reported in others. We examined the faster-Z effect in chameleons of the genus Furcifer, a lineage with differentiated ZZ/ZW chromosomes for at least 20 million years. We sequenced the genomes of four species of Furcifer chameleons in the Illumina platform and compared the substitution rates of synonymous and non-synonymous mutations and their ratios among autosomal, Z-specific, and pseudoautosomal protein-coding genes. The inclusion of two chameleon outgroups lacking the differentiated ZZ/ZW sex chromosomes allowed us to control for gene-specific evolutionary rates that might confound the testing of the faster-X/Z effect. Significant differences in evolutionary rates were found between autosomal, Z-specific, and pseudoautosomal genes of Furcifer chameleons. However, the inclusion of the outgroups with different sex chromosomes suggests that these genes had different evolutionary rates prior to their incorporation into the differentiated ZZ/ZW sex chromosomes of the Furcifer genus. The results highlight the need to control for differences in the evolutionary rates of individual genes when testing for the faster X/Z effect., (© The Author(s) 2024. Published by Oxford University Press on behalf of The American Genetic Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In response to our study, the commentary by Infanti et al. (2024) raised critical points regarding (i) the conceptualization and utility of the user-avatar bond in addressing gaming disorder (GD) risk, and (ii) the optimization of supervised machine learning techniques applied to assess GD risk. To advance the scientific dialogue and progress in these areas, the present paper aims to: (i) enhance the clarity and understanding of the concepts of the avatar, the user-avatar bond, and the digital phenotype concerning gaming disorder (GD) within the broader field of behavioral addictions, and (ii) comparatively assess how the user-avatar bond (UAB) may predict GD risk, by both removing data augmentation before the data split and by implementing alternative data imbalance treatment approaches in programming.

Background: Percutaneous rhizotomy of the Gasserian ganglion is a well-established intervention for patients suffering from refractory trigeminal pain, not amenable to pharmacological management or microvascular decompression. Traditionally conducted under fluoroscopic guidance using Hartel's technique, this study investigates a modified approach employing low-dose CT guidance to achieve maximal procedural precision and safety with the emphasis on minimizing radiation exposure., Methods: A retrospective analysis of patients undergoing percutaneous rhizotomy of the Gasserian ganglion at our institution was undertaken. Procedures were divided into fluoroscopy and CT-guided foramen ovale (FO) cannulation cohorts. Radiation doses were assessed, excluding cases with incomplete data. The study included 32 procedures in the fluoroscopy group and 30 in the CT group., Results: In the CT-guided group, the median effective dose was 0.21 mSv. The median number of CT scans per procedure was 4.5, and the median procedure time was 15 min. Successful FO cannulation was achieved in all 30 procedures (100%). In the fluoroscopy group, the median effective dose was 0.022 mSv, and the median procedure time was 15 min. Cannulation of FO was successful in 31 of 32 procedures (96.9%). The only complications in the CT-guided group were three minor cheek hematomas. Immediate pain relief in the CT-guided group was reported in 25 of 30 procedures (83.3%), 22 of 30 (73.3%) provided relief at one month, and 10 of 18 (55.6%) procedures resulting in pain relief at one month continued to provide relief after two years., Conclusion: Low-dose CT-guided percutaneous rhizotomy conducted in the radiology suite carries negligible radiation exposure for patients and eliminates it for personnel. This method is fast, simple, precise, and carries a very low risk of complications., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the University Hospital Pilsen and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Plasmodiophora brassicae, a soil-borne biotroph, establishes galls as strong physiological sinks on Brassicaceae plants including Brassica napus and Arabidopsis thaliana. We compare transcriptional profiles of phloem dissected from leaf petioles and hypocotyls of healthy and infected B. napus plants. Our results highlight how pathogenesis accompanies phloem-mediated defence responses whilst exerting a strong influence on carbon-nitrogen (C-N) economy. We observe transcriptional changes indicating decreased aliphatic glucosinolate biosynthesis, fluctuating jasmonic acid responses, altered amino acid (AA) and nitrate transport, carbohydrate metabolism and modified cytokinin responses. Changes observed in phloem-dissected from upper versus lower plant organs point to phloem as a conduit in mediating C-N repartitioning, nutrition-related signalling and cytokinin dynamics over long distances during clubroot disease. To assess changes in physiology, we measured AAs, sugars and cytokinins, in phloem exudates from B. napus plants. Despite the decrease in most AA and sucrose levels, isopentyl-type cytokinins increased within infected plants. Furthermore, we employed Arabidopsis for visualising promoter activities of B. napus AA and N transporter orthologues and tested the impact of disrupted cytokinin transport during P. brassicae-induced gall formation using Atabcg14 mutants. Our physiological and microscopy studies show that the host developmental reaction to P. brassicae relies on cytokinin and is accompanied by intense nitrogen and carbon repartitioning. Overall, our work highlights the systemic aspects of host responses that should be taken into account when studying clubroot disease., (© 2024 The Author(s). The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are intriguing compounds with potential pharmacological applications. While many RiPPs are known as antimicrobial agents, a limited number of RiPPs with anti-proliferative effects in cancer cells are available. Here we report the discovery of nostatin A (NosA), a highly modified RiPP belonging among nitrile hydratase-like leader peptide RiPPs (proteusins), isolated from a terrestrial cyanobacterium Nostoc sp. Its structure was established based on the core peptide sequence encoded in the biosynthetic gene cluster recovered from the producing strain and subsequent detailed nuclear magnetic resonance and high-resolution mass spectrometry analyses. NosA, composed of a 30 amino-acid peptide core, features a unique combination of moieties previously not reported in RiPPs: the simultaneous presence of oxazole/thiazole heterocycles, dehydrobutyrine/dehydroalanine residues, and a sactionine bond. NosA includes an isobutyl-modified proline residue, highly unusual in natural products. NosA inhibits proliferation of multiple cancer cell lines at low nanomolar concentration while showing no hemolysis. It induces cell cycle arrest in S-phase followed by mitochondrial apoptosis employing a mechanism different from known tubulin binding and DNA damaging compounds. NosA also inhibits Staphylococcus strains while it exhibits no effect in other tested bacteria or yeasts. Due to its novel structure and selective bioactivity, NosA represents an excellent candidate for combinatorial chemistry approaches leading to development of novel NosA-based lead compounds.

Introduction: This study was performed to compare the efficacy and safety of PreserFlo MicroShunt (PMS) implantation with mitomycin C (MMC) applied by sub-tenon injection versus conventional application by MMC-soaked sponges., Methods: This retrospective, 1-year cohort study included 100 eyes of 100 patients with glaucoma who underwent PMS implantation with MMC (0.4 mg/ml) delivered either by sub-tenon injection (50 eyes) or via soaked sponges (50 eyes). The primary outcome measure at 1 year was intraocular pressure (IOP) reduction, with complete success defined as an IOP reduction of ≥ 20% and achieving a target IOP of ≤ 21 or 18 mmHg without the use of medication. Secondary outcomes, including corneal endothelial cell density (CECD) loss, the number of medications, and complications, were assessed and compared between the groups., Results: Sustained reductions in mean IOP were observed in both groups over the 1-year follow-up, with no significant differences between the groups. The complete success rate, with a target IOP of ≤ 21 mmHg after 1 year, was 19.3% in the sponge group and 26.4% in the injection group. The qualified success rate was 59.0% and 87.4% in the sponge and injection groups, respectively. A longer survival rate was observed in the injection group than in the sponge group when IOP was below 21 mmHg. The mean CECD significantly decreased (P < 0.01) from baseline to each postoperative follow-up time point in both groups. At 1 year postoperatively, the percentage of total CECD loss was 8.1% in the sponge group and 8.0% in the injection group. However, no significant differences in mean CECD values, the number of medications, or adverse events were found between the groups., Conclusions: PMS implantation with sub-tenon injection of MMC was comparable in terms of efficacy and safety to traditional MMC delivery via soaked sponges. However, the injection group demonstrated a significantly higher success rate than the sponge group., Competing Interests: Declarations. Conflict of Interest: Nora Majtanova and Petr Kolar have the following financial disclosures: Alcon (honorarium); Santen (consultancy and honorarium) and Bayer (honorarium). Adriana Takacova has the following financial disclosures: Alcon (honorarium) and Santen (honorarium). Veronika Kurilova, Libor Hejsek, and Juraj Majtan have no competing interests. Ethical Approval: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of St. Cyril and Method University Hospital No. 1/9/20/24. Informed consent for surgical procedure was obtained from all subjects involved in the study., (© 2024. The Author(s).)

The expansion of human settlements over the past few centuries is responsible for an unprecedented number of invasive species introductions globally. An important component of biological invasion management is understanding how introduction history and postintroduction processes have jointly shaped present-day distributions and patterns of population structure, diversity and adaptation. One example of a successful invader is the European starling (Sturnus vulgaris), which was intentionally introduced to numerous countries in the 19th century, including Aotearoa New Zealand, where it has become firmly established. We used reduced representation sequencing to characterise the genetic population structure of the European starling in New Zealand, comparing it to that present in sampling locations in the native range and invasive Australian range. The population structure and genetic diversity patterns we found suggested restricted gene flow from the majority of New Zealand to the northmost sampling location (Auckland). We also profiled genetic bottlenecks and shared outlier genomic regions, which supported historical accounts of translocations between both Australian subpopulations and New Zealand, and provided evidence of which documented translocation events were more likely to have been successful. Using these results as well as historic demographic patterns, we demonstrate how genomic analysis complements even well-documented invasion histories to better understand invasion processes, with direct implications for understanding contemporary gene flow and informing invasion management., (© 2024 John Wiley & Sons Ltd.)

Cd toxicity emerges as a major environmental concern with detrimental impacts on global agricultural systems and food safety. Therefore, there is an urgent need to cope with the high concentration of Cd in the soil and crops. This study elucidates the potential of iron (FeBC) and zinc doped biochar (ZnBC) on the growth and yield of chickpea (Cicer arietinum L.) in Cd-contaminated soil. The parallels of biochemical attributes and Cd absorption of Cicer arietinum L. were investigated after a 120-day pot trial under 1% (w/w) biochar doses and two Cd concentrations (25 and 50 mg kg -1 ). The results demonstrated that FeBC was more effective in promoting plant growth by reducing Cd mobility in soil than ZnBC and normal biochar (NBC). Additionally, the application of FeBC resulted in significant improvement in photosynthesis rate (53.98%), transpiration rate (91.53%), stomatal conductance (197%), and sub-stomatal conductance (213.33%) compared to other applied treatments. Cd uptake in roots, shoots, and grains was reduced by 44.19%, 56.89%, and 88.25% respectively with the application of FeBC. Notably, the highest decrease in Cd bioaccumulation factor (99.72% and 99.65%) and Cd translocation factor (99.89% and 99.85%) were recorded under FeBC application in 25 and 50 mg kg -1 Cd-contaminated soils, respectively. The improved plant growth and reduced Cd buildup with FeBC under Cd stress suggest that FeBC is a promising strategy to remediate Cd-contaminated soil and simultaneously promote sustainable production of legume crops in Cd-contaminated soils., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Ticks obtain a blood meal by lacerating small blood vessels and ingesting the blood that flows to the feeding site, which triggers various host responses. However, ticks face the challenge of wound healing, a process involving hemostasis, inflammation, cell proliferation and migration, and remodeling, hindering blood acquisition. To overcome these obstacles, tick salivary glands produce an array of bioactive molecules. Here, we characterize ixochymostatin, an Ixodes scapularis protein belonging to the trypsin inhibitor-like (TIL) family. It is expressed in multiple developmental stages and in tick salivary glands and acts as a slow and tight-binding inhibitor of chymase, cathepsin G, and chymotrypsin. Predictions for the tertiary structure complex between ixochymostatin and chymase suggest a direct interaction between the inhibitor reactive site loop and protease active sites. In vitro, ixochymostatin protects the endothelial cell barrier against chymase degrading action, decreasing cell permeability. In vivo, it reduces vascular permeability induced by chymase and compound 48/80, a mast cell degranulator agonist, in a mouse model. Additionally, ixochymostatin inhibits the chymase-dependent generation of vasoconstrictor peptides. Antibodies against ixochymostatin neutralize its inhibitory properties, with epitope mapping identifying potential neutralization regions. Ixochymostatin emerges as a novel tick protein modulating host responses against tick feeding, facilitating blood acquisition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: This research aims to design and evaluate an enteric-coated hard capsule dosage form for targeted delivery of biological materials, such as FMT (fecal microbiota transplant) or live microbes, to the distal parts of the GIT. The capsules are designed to be internally protected against destruction by hydrophilic filling during passage through the digestive tract., Methods: Hard gelatin capsules and DRcaps TM capsules based on HPMC and gellan were used to encapsulate a hydrophilic body temperature-liquefying gelatin hydrogel with caffeine or insoluble iron oxide mixture. Different combinations of polymers were tested for the internal (ethylcellulose, Eudragit® E, and polyvinyl acetate) and external (Eudragit® S, Acryl-EZE®, and cellacefate) coating. The external protects against the acidic gastric environment, while the internal protects against the liquid hydrophilic filling during passage. Coated capsules were evaluated using standard disintegration and modified dissolution methods for delayed-release dosage forms., Results: Combining suitable internal (ethylcellulose 1.0 %) and external (Eudragit® S 20.0 %) coating of DRcaps TM capsules with the wiping and immersion method achieved colonic release times. While most coated capsules met the pharmaceutical requirements for delayed release, one combination stood out. Colonic times were indicated by the dissolution of soluble caffeine (during 120-720 min) measured by the dissolution method, and capsule rupture was indicated by the release of insoluble iron oxide (after 480 min) measured by the disintegration method. This promising result demonstrates the composition's suitability and potential to protect the content until it's released, inspiring hope for the future of colon-targeted delivery systems and its potential for the pharmaceutical and biomedical fields., Conclusion: Innovative and easy capsule coatings offer significant potential for targeted drugs, especially FMT water suspension, to the GIT, preferably the colon. The administration method is robust and not considerably affected by the quantity of internal or external coatings. It can be performed in regular laboratories without specialized individual and personalized treatment equipment, making it a practical and feasible method for drug delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Aim: To propose a standardized, high-resolution ultrasound (US) protocol to assess the patellar tendon-Hoffa fat pad interface (PTHFPI) in patients with (proximal) patellar tendinopathy (PPT)., Methods: Using a high-frequency transducer and a high-level machine, we matched the cadaveric and histological microarchitecture of the PTHFPI with multiple sonographic patterns of patients with PPT. Likewise, high-sensitive color/power Doppler assessments were also performed to evaluate the microcirculation of the soft tissues beneath the patellar tendon., Results: Modern US equipment allows for detailed assessment of the potential pain generators located inside the PTHFPI in patients with PPT. They include anterosuperior portion of the Hoffa body and the loose connective tissue of the deep paratenon with its microvascular plexus., Conclusions: In patients with PPT, accurate sonographic assessment of the PTHFPI can be performed using adequate technological equipment. Accordingly, tailored ultrasound-guided interventions can also be planned if/when clinically indicated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Findings on the link between the number of children and dementia risk are inconsistent, mostly studied in females, suggesting pregnancy-related changes may be a key factor in this association., Methods: The Adult Changes in Thought Study is a cohort of adults aged ≥65 years from Kaiser Permanente Washington. The primary exposure was the number of children (0, 1, 2, 3 or ≥4), and the outcome was an incident dementia diagnosis. Cox proportional-hazards models were adjusted for demographic and early-life socioeconomic confounders. Models were then stratified by sex and by birth year <1928 versus ≥1928., Results: Among 4668 participants (average age at enrolment 74.1±SD 6.3 years; 59% female), 967 (21%) had 0 children, 484 (10%) had one child, 1240 (27%) had two children, 968 (21%) had three children and 1009 (22%) had four or more children. We found no association between the number of children and dementia overall or after stratification by birth cohort. When stratified by sex and adjusting for confounders, having ≥4 children compared with two children was associated with a higher rate of dementia in males (HR=1.31, 95% CI 1.01 to 1.71)., Conclusions: The number of children was not consistently associated with the risk of dementia. We observed a greater risk of dementia only among males who had ≥4 children, with the lower bound of the 95% CI marginally exceeding 1. These findings suggest that the number of children may influence the risk of dementia through other than pregnancy-related pathways., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The magnetic field-induced modification of the electric-dipole forbidden transitions between the lowest rotational states of the 2 Π 1/2 and the 2 Π 3/2 substates of a 2 Π diatomic radical is probed by model calculations for the ground electronic states of NO, OH and CH. Magnetic fields in the range of 0-12 T and more were considered and the intensities of the respective allowed rotational transitions for the given systems were calculated for comparison. In particular, NO shows enhanced field dependence of calculated intensities.

In nature and many technological applications, aqueous solutions are in contact with patterned surfaces, which are dynamic over time scales spanning from ps to μs. For instance, in biology, exposed polar and apolar residues of biomolecules form a pattern, which fluctuates in time due to side chain and conformational motions. At metal/and oxide/water interfaces, the pattern is formed by surface topmost atoms, and fluctuations are due to, e.g., local surface polarization and rearrangements in the adsorbed water layer. All these dynamics have the potential to influence key processes such as wetting, energy relaxation, and biological function. Yet, their impact on the water H-bond network remains often elusive. Here, we leverage molecular dynamics to address this fundamental question at a self-assembled monolayer (SAM)/water interface, where ns dynamics is induced by frustrating SAM-water interactions via methylation of the terminal -OH groups of poly(ethylene glycol) (PEG) chains. We find that surface dynamics couples to the water H-bond network, inducing a response on the same ns time scale. This leads to time fluctuations of local wetting, oscillating from hydrophobic to hydrophilic environments. Our results suggest that rather than average properties, it is the local─ both in time and space─ solvation that determines the chemical-physical properties of dynamically patterned surfaces in water.

Novel ionene-type cationic copolyimides based on 4,4'-oxydiphthalic anhydride (ODPA), 4,4'-(1,4-phenylenediisopropylidene)bisaniline (BIS P), and 2,6-diaminopyridine (DAP) were synthesized. The copolyimides were obtained in two stages: first, the copolyimides with the 0/1, 0.2/0.8, 0.3/0.7, 0.5/0.5, 0.6/0.4 and 1/0 DAP/Bis P ratios were obtained through thermal imidization, and then quaternization of soluble copolyimides with methyl iodide was conducted for 24 or 48 h. The samples were characterized via FTIR, NMR and EDX methods to confirm their structure and composition. The cationic copolyimides with a DAP content of less than 0.3 showed initial weight loss (onset) at about 250 °C, according to TGA results and demonstrated solubility in chloroform. The highest ionic conductivity value of 0.234 S cm -1 was showed by the sample with 0.3 DAP content and 0.15 degree of quaternization. The stability of the membranes in alkaline media was evaluated using FTIR and TGA. It was shown that samples with a DAP content of more than 0.3 lost their integrity probably owing to partial hydrolysis of imide rings, while copolyimides with a DAP content of 0.2 and 0.3 remained stable., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Nanostructured materials with antibacterial activity face the same threat as conventional antibiotics - bacterial resistance, which reduces their effectiveness. However, unlike antibiotics, research into the emergence and mechanisms of bacterial resistance to antibacterial nanomaterials is still in its early stages. Here we show how Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria develop resistance to silver nanoparticles, resulting in an increase in the minimum inhibitory concentration from 1.69 mg/L for S. aureus and 3.38 mg/L for E. coli to 54 mg/L with repeated exposure over 12 and 6 cultivation steps, respectively. The mechanism of resistance is the same for both types of bacteria and involves the aggregation of silver nanoparticles leading to the formation of black precipitates. However, the way in which Gram-positive and Gram-negative bacteria induce aggregation of silver nanoparticles is completely different. Chemical analysis of the surface of the silver precipitates shows that aggregation is triggered by flagellin production in E. coli and by bacterial biofilm formation in S. aureus. However, resistance in both types of bacteria can be overcome by using pomegranate rind extract, which inhibits both flagellin and biofilm production, or by stabilizing the silver nanoparticles by covalently binding them to a composite material containing graphene sheets, which protects the silver nanoparticles from aggregation induced by the bacterial biofilm produced by S. aureus. This research improves the understanding of bacterial resistance mechanisms to nanostructured materials, which differ from resistance mechanisms to conventional antibiotics, and provides potential strategies to combat bacterial resistance and develop more effective antimicrobial treatments., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The production of high-quality crystals is a key step in crystallography in general, but control of crystallization conditions is even more crucial in serial crystallography, which requires sets of crystals homogeneous in size and diffraction properties. This protocol describes the implementation of a simple and user-friendly microfluidic device that allows both the production of crystals by the counter-diffusion method and their in situ analysis by serial crystallography. As an illustration, the whole procedure is used to determine the crystal structure of three proteins from data collected at room temperature at a synchrotron radiation source., (© 2024 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Age-related macular degeneration (AMD) is a progressive chronic disease causing visual impairment or central vision loss in the elderly. We hypothesized that successful rheopheresis would be associated with positive changes in soluble endoglin (sENG), PSCK9, alpha-2-macroglobulin (A2M), and hs-CRP levels. 31 elderly patients with the dry form of AMD, treated with rheopheresis with a follow-up period of at least 5 years and an average age of 68 ± 4 years, were evaluated. Each treated patient received a series of 8 procedures in 10 weeks and, after the 2-year period, another 2 procedures within 1 week. Then, the patients were followed up every 6 months and divided into the successfully treated and therapeutic failure group according to best-corrected visual acuity (BCVA), size of the drusen area, and the drusenoid pigment epithelium detachment (DPED). Based on the ophthalmological assessment, rheopheresis treatment was successful in 73% of AMD patients. The therapy was associated with a significant decrease in total cholesterol, LDL-C, HDL-C, apoprotein B, lipoprotein (a) levels, and rheologically important parameters, irrespective of the therapy's success or failure. The success of rheopheresis therapy was exclusively related to a significant decrease in sENG and A2M levels. Over the long term, rheopheresis prevented the decline of BCVA, reduced the DPED and area of macular drusen, and improved the preservation of an intact photoreceptor ellipsoid zone in most patients. Moreover, we showed for the first time that sENG and A2M could be potentially sensitive biomarkers of successful rheopheresis procedure, irrespective of lipid parameters changes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The protocol was carried out according to the Declaration of Helsinki. All participants gave written informed consent, which, together with the protocol of the study, were approved by the institute’s ethics committee (approval number 201607 S03P). The study has been registered under Clinical Trial Registration number NCT01943396 (17/09/2013). https://classic.clinicaltrials.gov/ct2/show/NCT01943396?cond=Age-Related+Macular+Degeneration&cntry=CZ&draw=2&rank=1, (© 2024. The Author(s).)

Three series of spiropyran photoswitches with an auxiliary chiral centre at position 3' of the indoline unit were synthesized. Using one example, a novel methodology for synthesis of an optically active spiropyran photoswitch with a defined chirality at position 3' is demonstrated. Furthermore, a new acid-mediated strategy for spiropyran purification affording moderate to excellent yields (up to 96%) is reported herein. Relative diastereomeric ratios of the prepared spiropyrans were evaluated using NMR spectroscopy in five different solvents ( syn  :  anti up to 21 : 79) and their photoswitching properties determined by UV-vis spectroscopy. It was found that substitution at position 8 of the chromene subunit notably accelerates the photoswitching process., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)