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Infinite-dimensional systems play an important role in the continuous-variable quantum computation model, which can compete with a more standard approach based on qubit and quantum circuit computation models. But, in many cases, the value of entropy unfortunately cannot be easily computed for states originating from an infinite-dimensional Hilbert space. Therefore, in this article, the unified quantum entropy (which extends the standard von Neumann entropy) notion is extended to the case of infinite-dimensional systems by using the Fredholm determinant theory. Some of the known (in the finite-dimensional case) basic properties of the introduced unified entropies were extended to this case study. Certain numerical examples for computing the proposed finite- and infinite-dimensional entropies are outlined as well, which allowed us to calculate the entropy values for infinite Hilbert spaces. [ABSTRACT FROM AUTHOR]

Enzymes capable of processing a variety of compounds enable plants to adapt to diverse environmental conditions. PRISEs (progesterone-5β-reductase/iridoid synthase-like enzymes), examples of such substrate-promiscuous enzymes, are involved in iridoid and cardenolide pathways and demonstrate notable substrate promiscuity by reducing the activated C=C double bonds of plant-borne and exogenous 1,4-enones. In this study, we identified PRISE genes in Plantago media (PmdP5βR1) and Plantago lanceolata (PlP5βR1), and the corresponding enzymes were determined to share a sequence identity of 95%. Despite the high sequence identity, recombinant expressed PmdP5βR1 was 70 times more efficient than PlP5βR1 for converting progesterone. In order to investigate the underlying reasons for this significant discrepancy, we focused on specific residues located near the substrate-binding pocket and adjacent to the conserved phenylalanine "clamp". This clamp describes two phenylalanines influencing substrate preferences by facilitating the binding of smaller substrates, such as 2-cyclohexen-1-one, while hindering larger ones, such as progesterone. Using structural analysis based on templates PDB ID: 5MLH and 6GSD from PRISE of Plantago major, along with in silico docking, we identified positions 156 and 346 as hot spots. In PlP5βR1 amino acid residues, A156 and F346 seem to be responsible for the diminished ability to reduce progesterone. Moreover, the double mutant PlP5βR_F156L_A346L, which contains the corresponding amino acids from PmdP5βR1, showed a 15-fold increase in progesterone 5β-reduction. Notably, this modification did not significantly alter the enzyme's ability to convert other substrates, such as 8-oxogeranial, 2-cyclohexen-1-one, and methyl vinyl ketone. Hence, a rational enzyme design by reducing the number of hotspots selectively, specifically improved the substrate preference of PlP5βR1 for progesterone. [ABSTRACT FROM AUTHOR]

Objectives: Blood pressure (BP) management is challenging in patients with acute ischemic supratentorial stroke undergoing recanalization therapy due to the lack of established guidelines. Assessing dynamic cerebral autoregulation (dCA) may address this need, as it is a bedside technique that evaluates the transfer function phase in the very low-frequency (VLF) range (0.02–0.07 Hz) between BP and cerebral blood flow velocity (CBFV) in the middle cerebral artery. This phase is a prognostically relevant parameter, with lower values associated with poorer outcomes. This study aimed to evaluate whether early cranial computed tomography perfusion (CTP) can predict this parameter. Methods: In this retrospective study, 165 consecutive patients with hemispheric strokes who underwent recanalizing therapy were included (median age: 73 years; interquartile range (IQR) 60–80; women: 43 (26%)). The cohort comprised 91 patients treated with intravenous thrombolysis (IV-lysis) alone (median National Institute of Health Stroke Scale (NIHSS) score: 5; IQR 3–7) and 74 patients treated with mechanical thrombectomy (median NIHSS: 15; IQR 9–18). Regression analysis was performed to assess the relationship between pretreatment CTP-derived ischemic penumbra and core stroke volumes and the dCA VLF phase, as well as CBFV assessed within the first 72 h post-stroke event. Results: Pretreatment penumbra volume was a significant predictor of the VLF phase (adjusted r2 = 0.040; β = −0.001, 95% confidence interval (CI): −0.0018 to −0.0002, p = 0.02). Core infarct volume was a stronger predictor of CBFV (adjusted r2 = 0.082; β = 0.205, 95% CI: 0.0968–0.3198; p = 0.0003) compared to penumbra volume (p = 0.01). Additionally, in the low-frequency range (0.07–0.20 Hz), CBFV and BP were inversely related to the gain, an index of vascular tone. Conclusion: CTP metrics appear to correlate with the outcome-relevant VLF phase and reactive hyperemic CBFV, which interact with BP to influence vascular tone and gain. These aspects of dCA could potentially guide BP management in patients with acute stroke undergoing recanalization therapy. However, further validation is required. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease (CD) is a complex systemic entity, characterized by the progressive and relapsing inflammatory involvement of any part of the gastrointestinal tract. Its clinical pattern may be categorized as penetrating, stricturing or non-penetrating non-stricturing. Methods: In this paper, we performed a database search (Pubmed, MEDLINE, Mendeley) using combinations of the queries "crohn", "stricture" and "elastography" up to 19 June 2024 to summarize current knowledge regarding the diagnostic utility of ultrasound (US) and magnetic resonance (MR) elastography techniques in the evaluation of stricturing CD by means of an assessment of the transmural intestinal fibrosis. We decided to include papers published since 1 January 2017 for further evaluation (n = 24). Results: Despite growing collective and original data regarding numerous applications of mostly ultrasound elastography (quantification of fibrosis, distinguishing inflammatory from predominantly fibrotic strictures, assessment of treatment response, predicting disease progression) constantly emerging, to date, we are still lacking a uniformization in both cut-off values and principles of measurements, i.e., reference tissue in strain elastography (mesenteric fat, abdominal muscles, unaffected bowel segment), units, not to mention subtle differences in technical background of SWE techniques utilized by different vendors. All these factors imply that ultrasound elastography techniques are hardly translatable throughout different medical centers and practitioners, largely depending on the local experience. Conclusions: Nonetheless, the existing medical evidence is promising, especially in terms of possible longitudinal comparative studies (follow-up) of patients in the course of the disease, which seems to be of particular interest in children (lack of radiation, less invasive contrast media) and terminal ileal disease (easily accessible). [ABSTRACT FROM AUTHOR]

Biomaterials play an important role in treating bone defects. The functional characteristics of scaffolds, such as their structure, mechanical strength, and antibacterial and osteogenesis activities, effectively promote bone regeneration. In this study, mineralized collagen and polycaprolactone were used to prepare loaded porous scaffolds with bilayer-structured microspheres with dual antibacterial and osteogenesis functions. The different drug release mechanisms of PLGA and chitosan in PLGA/CS microspheres caused differences in the drug release models in terms of the duration and rate of Pac-525 and BMP-2 release. The prepared PLGA(BMP-2)/CS(Pac-525)@MC/PCL scaffolds were analyzed in terms of physical characteristics, bioactivity, and antibacterial properties. The scaffolds with a dimensional porous structure showed similar porosity and pore diameter to cancellous bone. The release curve of the microspheres and scaffolds with high encapsulation rates displayed the two-stage release of Pac-525 and BMP-2 over 30 days. It was found that the scaffolds could inhibit S. aureus and E. coli and then promote ALP activity. The PLGA(BMP-2)/CS(Pac-525)@MC/PCL scaffold could be used as a dual delivery system to promote bone regeneration. [ABSTRACT FROM AUTHOR]

The objective of this review is to examine the connection between osteoporosis and diabetes, compare the underlying causes of osteoporosis in various forms of diabetes, and suggest optimal methods for diagnosing and assessing fracture risk in diabetic patients. This narrative review discusses the key factors contributing to the heightened risk of fractures in individuals with diabetes, as well as the shared elements impacting the treatment of both diabetes mellitus and osteoporosis. Understanding the close link between diabetes and a heightened risk of fractures is crucial in effectively managing both conditions. There are several review articles of meta-analysis regarding diaporosis. Nevertheless, no review articles showed collected and well-organized medications of antidiabetics and made for inconvenient reading for those who were interested in details of drug mechanisms. In this article, we presented collected and comprehensive charts of every antidiabetic medication which was linked to fracture risk and indicated plausible descriptions according to research articles. [ABSTRACT FROM AUTHOR]

Simple Summary: Environmental factors, maternal inheritance, and feeding success are influential factors in fish growth, especially during the larval stage, encompassing their early days of life. Growth rates play a crucial role in larval survival, particularly in species with high energy requirements such as the Atlantic bluefin tuna (ABFT). Our analyses of two patches of ABFT larvae collected in the Gulf of Mexico's spawning region during different years reveal variable larval growth, depending on prey availability. Larval growth also shows a direct relationship to maternal feeding. Estimates of larval trophic positions are primarily influenced by food web length and energy transmission efficiency, leading to differences in larval growth and underscoring the importance of considering trophic dynamics in interpreting results. These findings offer novel insights into how these factors affect ABFT larval growth, potentially informing conservation efforts and fisheries management strategies by governmental institutions. Two cohorts of Atlantic bluefin tuna (Thunnus thynnus) larvae were sampled in 2017 and 2018 during the peak of spawning in the Gulf of Mexico (GOM). We examined environmental variables, daily growth, otolith biometry and stable isotopes and found that the GOM18 cohort grew at faster rates, with larger and wider otoliths. Inter and intra-population analyses (deficient vs. optimal growth groups) were carried out for pre- and post-flexion developmental stages to determine maternal and trophodynamic influences on larval growth variability based on larval isotopic signatures, trophic niche sizes and their overlaps. For the pre-flexion stages in both years, the optimal growth groups had significantly lower δ15N, implying a direct relationship between growth potential and maternal inheritance. Optimal growth groups and stages for both years showed lower C:N ratios, reflecting a greater energy investment in growth. The results of this study illustrate the interannual transgenerational trophic plasticity of a spawning stock and its linkages to growth potential of their offsprings in the GOM. [ABSTRACT FROM AUTHOR]

Circulating cell-free DNA (ccfDNA) of mitochondrial origin (ccf-mtDNA) consists of a minor fraction of total ccfDNA in blood or in other biological fluids. Aberrant levels of ccf-mtDNA have been observed in many pathologies. Here, we introduce a simple and effective standardized Taqman probe-based dual-qPCR assay for the simultaneous detection and relative quantification of nuclear and mitochondrial fragments of ccfDNA. Three pathologies of major burden, one malignancy (Breast Cancer, BrCa), one inflammatory (Osteoarthritis, OA) and one metabolic (Type 2 Diabetes, T2D), were studied. Higher levels of ccf-mtDNA were detected both in BrCa and T2D in relation to health, but not in OA. In BrCa, hormonal receptor status was associated with ccf-mtDNA levels. Machine learning analysis of ccf-mtDNA datasets was used to build biosignatures of clinical relevance. (A) a three-feature biosignature discriminating between health and BrCa (AUC: 0.887) and a five-feature biosignature for predicting the overall survival of BrCa patients (Concordance Index: 0.756). (B) a five-feature biosignature stratifying among T2D, prediabetes and health (AUC: 0.772); a five-feature biosignature discriminating between T2D and health (AUC: 0.797); and a four-feature biosignature identifying prediabetes from health (AUC: 0.795). (C) a biosignature including total plasma ccfDNA with very high performance in discriminating OA from health (AUC: 0.934). Aberrant ccf-mtDNA levels could have diagnostic/prognostic potential in BrCa and Diabetes, while the developed multiparameter biosignatures can add value to their clinical management. [ABSTRACT FROM AUTHOR]

Intestinal ultrasound is a non-invasive, safe, and cost-effective technique to study the small and large intestines. In addition to conventional B-mode and color doppler imaging, new US tools have been developed in more recent years that provide auxiliary data on many GI conditions, improving the diagnosis and assessment of relevant outcomes. We have reviewed the more recent literature (from 2010 onwards) on auxiliary tools in bowel ultrasound such as elastography techniques, CEUS, SICUS, and the potential contribution by artificial intelligence (AI) to overcome current intestinal ultrasound limitations. For this scoping review, we performed an extensive literature search on PubMed and EMBASE to identify studies published until December 2023 and investigating the application of elastography techniques, CEUS, SICUS, and AI in the ultrasonographic assessment of the small and large intestines. Multiparametric intestinal ultrasound shows promising capabilities in Crohn's disease, while less is known about the role in ulcerative colitis. Despite some evidence, the CEUS role as a point-of-care examination tool for rare conditions such as intestinal GvHD and ischemic small bowel disease seems promising, possibly avoiding the need to perform further cross-sectional imaging. The use of AI in intestinal ultrasound is still anecdotical and limited to acute appendicitis. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD), especially Crohn's disease (CD), characterized by a chronic inflammatory process and progressive intestinal tissue damage, leads to the unrestrained proliferation of mesenchymal cells and the development of bowel strictures. Complications induced by fibrosis are related to high rates of morbidity and mortality and lead to a substantial number of hospitalizations and surgical procedures, generating high healthcare costs. The development of easily obtained, reliable fibrogenesis biomarkers is essential to provide an important complementary tool to existing diagnostic and prognostic methods in IBD management, guiding decisions on the intensification of pharmacotherapy, proceeding to surgical methods of treatment and monitoring the efficacy of anti-fibrotic therapy in the future. The most promising potential markers of fibrosis include cartilage oligomeric matrix protein (COMP), hepatocyte growth factor activator (HGFA), and fibronectin isoform- extra domain A (ED-A), as well as antibodies against granulocyte macrophage colony-stimulating factor (GM-CSF Ab), cathelicidin (LL-37), or circulatory miRNAs: miR-19a-3p and miR-19b-3p. This review summarizes the role of genetic predisposition, and risk factors and serological markers potentially contributing to the pathophysiology of fibrotic strictures in the course of IBD. [ABSTRACT FROM AUTHOR]

Liquid biopsies, in particular the profiling of circulating tumor DNA (ctDNA), have long held promise as transformative tools in cancer precision medicine. Despite a prolonged incubation phase, ctDNA profiling has recently experienced a strong wave of development and innovation, indicating its imminent integration into the cancer management toolbox. Various advancements in mutation-based ctDNA analysis methodologies and technologies have greatly improved sensitivity and specificity of ctDNA assays, such as optimized preanalytics, size-based pre-enrichment strategies, targeted sequencing, enhanced library preparation methods, sequencing error suppression, integrated bioinformatics and machine learning. Moreover, research breakthroughs have expanded the scope of ctDNA analysis beyond hotspot mutational profiling of plasma-derived apoptotic, mono-nucleosomal ctDNA fragments. This broader perspective considers alternative genetic features of cancer, genome-wide characterization, classical and newly discovered epigenetic modifications, structural variations, diverse cellular and mechanistic ctDNA origins, and alternative biospecimen types. These developments have maximized the utility of ctDNA, facilitating landmark research, clinical trials, and the commercialization of ctDNA assays, technologies, and products. Consequently, ctDNA tests are increasingly recognized as an important part of patient guidance and are being implemented in clinical practice. Although reimbursement for ctDNA tests by healthcare providers still lags behind, it is gaining greater acceptance. In this work, we provide a comprehensive exploration of the extensive landscape of ctDNA profiling methodologies, considering the multitude of factors that influence its development and evolution. By illuminating the broader aspects of ctDNA profiling, the aim is to provide multiple entry points for understanding and navigating the vast and rapidly evolving landscape of ctDNA methodologies, applications, and technologies. [ABSTRACT FROM AUTHOR]

Mitochondria are the bioenergetic organelles responsible for the maintenance of cellular homeostasis and have also been found to be associated with inflammation. They are necessary to induce and maintain innate and adaptive immune cell responses, acting as signalling platforms and mediators in effector responses. These organelles are also known to play a pivotal role in cation homeostasis as well, which regulates the inflammatory responses through the modulation of these cation channels. In particular, this review focuses on mitochondrial Ca2+ and K+ fluxes in the regulation of inflammatory response. Nevertheless, this review aims to understand the interplay of these inflammation inducers and pathophysiological conditions. In detail, we discuss some examples of chronic inflammation such as lung, bowel, and metabolic inflammatory diseases caused by a persistent activation of the innate immune response due to a dysregulation of mitochondrial cation homeostasis. [ABSTRACT FROM AUTHOR]

The widespread use of immunosuppressive drugs makes it possible to reduce inflammation in autoimmune diseases, as well as prevent transplant rejection in organ recipients. Despite their key action in blocking the body's immune response, these drugs have many side effects. These actions primarily affect the cardiovascular system, and the incidence of complications in patients using immunosuppressive drugs is significant, being associated with a higher incidence of cardiovascular incidents such as myocardial infarction and stroke. This paper analyzes the mechanisms of action of commonly used immunosuppressive drugs and their impact on the cardiovascular system. The adverse effect of immunosuppressive drugs is associated with toxicity within the cardiovascular system, which may be a problem in the clinical management of patients after transplantation. Immunosuppressants act on the cardiovascular system in a variety of ways, including fibrosis and myocardial remodeling, endothelium disfunction, hypertension, atherosclerosis, dyslipidemia or hyperglycaemia, metabolic syndrome, and hyperuricemia. The use of multidrug protocols makes it possible to develop regimens that can reduce the incidence of cardiovascular events. A better understanding of their mechanism of action and the range of complications could enable physicians to select the appropriate therapy for a given patient, as well as to reduce complications and prolong life. [ABSTRACT FROM AUTHOR]

In order to alleviate the serious problem of scaling in oilfield water injection pipelines, we developed a scale collection device and applied it in the field based on the idea to "change passive descaling to active descaling", but the effect is not stable, so we need to improve the descaling effect. Firstly, this paper analyzed the effect of surface physical properties of eight non-metallic materials on CaCO3 scale growth and their mechanisms through shear experiments. Then, the influence of surface properties (roughness, contact angle, surface energy) on the scale growth characteristics was investigated. Finally, the influence of material surface properties on the friction coefficient was studied by a cyclic experiment. The results showed that except for PTFE (polytetrafluoroethylene), the fouling amount of the other seven materials changed abruptly at 18 h, and the maximum fouling amount of FRP was 2.05 g/m3. It was found by scanning electron microscopy that the fouling particles on the surface of FRP were interconnected and presented in the form of flakes, which was related to the larger surface wettability, surface energy, and roughness. At the same time, the surface properties of the material have a certain relationship with the friction coefficient, and the influence of the contact angle on the friction coefficient is greater than the surface energy and roughness. [ABSTRACT FROM AUTHOR]

Ultrasound imaging is the first-line investigation for patients with abdominal symptoms, as it effectively depicts the gastrointestinal tract and enables the diagnosis of multiple pathological conditions. Among different recent ultrasound technological advancements, elastography enables the evaluation of various tissue characteristics, such as neoplastic transformation or fibroinflammatory status. In recent years, ultrasound elastography has been utilized extensively for the study of liver diseases and in numerous other clinical settings, including gastrointestinal diseases. Current guidelines suggest the use of transabdominal ultrasound elastography to characterize bowel wall lesions, to assess gastrointestinal contractility, to diagnose and grade chronic pancreatitis; however, no specific indications are provided. In the present paper, we summarize the evidence concerning the application of different ultrasound elastography modalities in gastrointestinal non-liver diseases. [ABSTRACT FROM AUTHOR]

In this review, we will describe the importance of fibrosis in inflammatory bowel disease (IBD) by discussing its distinct impact on Crohn's disease (CD) and ulcerative colitis (UC) through their translation to histopathology. We will address the existing knowledge on the correlation between inflammation and fibrosis and the still not fully explained inflammation-independent fibrogenesis. Finally, we will compile and discuss the recent advances in the noninvasive assessment of intestinal fibrosis, including imaging and biomarkers. Based on the available data, none of the available cross-sectional imaging (CSI) techniques has proved to be capable of measuring CD fibrosis accurately, with MRE showing the most promising performance along with elastography. Very recent research with radiomics showed encouraging results, but further validation with reliable radiomic biomarkers is warranted. Despite the interesting results with micro-RNAs, further advances on the topic of fibrosis biomarkers depend on the development of robust clinical trials based on solid and validated endpoints. We conclude that it seems very likely that radiomics and AI will participate in the future non-invasive fibrosis assessment by CSI techniques in IBD. However, as of today, surgical pathology remains the gold standard for the diagnosis and quantification of intestinal fibrosis in IBD. [ABSTRACT FROM AUTHOR]

Derived Hench bioactive glass (BaG) containing boron (B) is explored in this work as it plays an important role in bone development and regeneration. B was also found to enhance BaG dissociation. However, it is only possible to incorporate a limited amount of B. To increase the amount of B in BaG, bioactive borosilicate glasses (BaG-Bx) were fabricated based on the use of the solution-gelation process (sol-gel). In this work, a high B content (20 wt.%) in BaG, respecting the conditions of bioactivity and biodegradability required by Hench, was achieved for the first time. The capability of BaG-Bx to form an apatite phase was assessed in vitro by immersion in simulated body fluid (SBF). Then, the chemical structure and the morphological changes in the fabricated BaG-Bx (x = 0, 5, 10 and 20) were studied. The formation of hydroxyapatite (HAp) layer was observed with X-ray diffraction (XRD) and infrared (IR) spectroscopy. The presence of HAp layer was confirmed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Enhanced bioactivity and chemical stability of BaG-Bx were evaluated with an ion exchange study based on Inductively Coupled Plasma–Optical Emission Spectrometry (ICP-OES) and energy dispersive spectroscopy (EDS). Results indicate that by increasing the concentration of B in BaG-Bx, the crystallization rate and the quality of the newly formed HAp layer on BaG-Bx surfaces can be improved. The presence of B also leads to enhanced degradation of BaGs in SBF. Accordingly, BAG-Bx can be used for bone regeneration, especially in children, because of its faster degradation as compared to B-free glass. [ABSTRACT FROM AUTHOR]

Human nutrition, and what can be considered "ideal" nutrition, is a complex, multi-faceted topic which many researchers and practitioners deliberate. While some attest that basic human nutrition is relatively understood, it is undeniable that a global nutritional problem persists. Many countries struggle with malnutrition or caloric deficits, while others encounter difficulties with caloric overconsumption and micronutrient deficiencies. A multitude of factors contribute to this global problem. Limitations to the current scope of the recommended daily allowances (RDAs) and dietary reference intakes (DRIs), changes in soil quality, and reductions in nutrient density are just a few of these factors. In this article, we propose a new, working approach towards human nutrition designated "Foundational Nutrition". This nutritional lens combines a whole food approach in conjunction with micronutrients and other nutrients critical for optimal human health with special consideration given to the human gut microbiome and overall gut health. Together, this a synergistic approach which addresses vital components in nutrition that enhances the bioavailability of nutrients and to potentiate a bioactive effect. [ABSTRACT FROM AUTHOR]

The objective of this study is to provide an updated account of the distribution history of two invasive molluscs, Corbicula fluminea and Dreissena polymorpha, both in Europe and worldwide. In addition to this, the study also intends to review their ecological requirements to gain a better understanding of their invasive potential and distribution dynamics. Specifically, the study focuses on updating the distribution and ecological characteristics of these freshwater bivalves in the lower sector of the Danube River and the lakes of the Danube Delta. The purpose is to better understand their invasive and distribution dynamics and to develop effective measures to limit their spread in the future. To achieve this, environmental proxies such as sediment particle size and Total Organic Carbon (TOC) concentrations were used to assess their tolerances. However, the results did not show a significant correlation between the densities of these bivalves and the analyzed environmental parameters. Despite this, the species were found in high densities and formed well-developed benthic communities in some stations. The study contributes to the understanding of the invasiveness of these bivalve species and their distribution range dynamics. Nonetheless, further investigation is required to fully comprehend the role of environmental parameters in their distribution. The study covers the period between 2010 and 2020 and focuses on the lower Danube River sector and Danube Delta. [ABSTRACT FROM AUTHOR]

Background: Obese and pre-diabetic women have a higher risk for cardiovascular death than age-matched men with the same symptoms, and there are no effective treatments. We reported that obese and pre-diabetic female Zucker Diabetic Fatty (ZDF-F) rats recapitulate metabolic and cardiac pathology of young obese and pre-diabetic women and exhibit suppression of cardio-reparative AT2R. Here, we investigated whether NP-6A4, a new AT2R agonist with the FDA designation for pediatric cardiomyopathy, mitigate heart disease in ZDF-F rats by restoring AT2R expression. Methods: ZDF-F rats on a high-fat diet (to induce hyperglycemia) were treated with saline, NP-6A4 (10 mg/kg/day), or NP-6A4 + PD123319 (AT2R-specific antagonist, 5 mg/kg/day) for 4 weeks (n = 21). Cardiac functions, structure, and signaling were assessed by echocardiography, histology, immunohistochemistry, immunoblotting, and cardiac proteome analysis. Results: NP-6A4 treatment attenuated cardiac dysfunction, microvascular damage (−625%) and cardiomyocyte hypertrophy (−263%), and increased capillary density (200%) and AT2R expression (240%) (p < 0.05). NP-6A4 activated a new 8-protein autophagy network and increased autophagy marker LC3-II but suppressed autophagy receptor p62 and autophagy inhibitor Rubicon. Co-treatment with AT2R antagonist PD123319 suppressed NP-6A4's protective effects, confirming that NP-6A4 acts through AT2R. NP-6A4-AT2R-induced cardioprotection was independent of changes in body weight, hyperglycemia, hyperinsulinemia, or blood pressure. Conclusions: Cardiac autophagy impairment underlies heart disease induced by obesity and pre-diabetes, and there are no drugs to re-activate autophagy. We propose that NP-6A4 can be an effective drug to reactivate cardiac autophagy and treat obesity- and pre-diabetes-induced heart disease, particularly for young and obese women. [ABSTRACT FROM AUTHOR]

As non-unions are still common, a predictive assessment of healing complications could enable immediate intervention before negative impacts for the patient occur. The aim of this pilot study was to predict consolidation with the help of a numerical simulation model. A total of 32 simulations of patients with closed diaphyseal femoral shaft fractures treated by intramedullary nailing (PFNA long, FRN, LFN, and DePuy Synthes) were performed by creating 3D volume models based on biplanar postoperative radiographs. An established fracture healing model, which describes the changes in tissue distribution at the fracture site, was used to predict the individual healing process based on the surgical treatment performed and full weight bearing. The assumed consolidation as well as the bridging dates were retrospectively correlated with the clinical and radiological healing processes. The simulation correctly predicted 23 uncomplicated healing fractures. Three patients showed healing potential according to the simulation, but clinically turned out to be non-unions. Four out of six non-unions were correctly detected as non-unions by the simulation, and two simulations were wrongfully diagnosed as non-unions. Further adjustments of the simulation algorithm for human fracture healing and a larger cohort are necessary. However, these first results show a promising approach towards an individualized prognosis of fracture healing based on biomechanical factors. [ABSTRACT FROM AUTHOR]

(1) Background: Interventional endoscopic procedures are growing more popular, requiring innovative instruments and novel techniques. Three-dimensional printing has demonstrated great potential for the rapid development of prototypes that can be used for the early assessment of various concepts. In this work, we present the development of a flexible endoscopic instrument and explore its potential benefits. (2) Methods: The properties of the instrument, such as its maneuverability, flexibility, and bending force, were evaluated in a series of bench tests. Additionally, the effectiveness of the instrument was evaluated in an ex vivo porcine model by medical experts, who graded its properties and performance. Furthermore, the time necessary to complete various interventional endoscopic tasks was recorded. (3) Results: The instrument achieved bending angles of ±216° while achieving a bending force of 7.85 (±0.53) Newtons. The time needed to reach the operating region was 120 s median, while it took 70 s median to insert an object in a cavity. Furthermore, it took 220 s median to insert the instrument and remove an object from the cavity. (4) Conclusions: This study presents the development of a flexible endoscopic instrument using three-dimensional printing technology and its evaluation. The instrument demonstrated high bending angles and forces, and superior properties compared to the current state of the art. Furthermore, it was able to complete various interventional endoscopic tasks in minimal time, thus potentially leading to the improved safety and effectiveness of interventional endoscopic procedures in the future. [ABSTRACT FROM AUTHOR]

Cancer is a highly heterogeneous disease, and thus treatment responses vary greatly between patients. To improve therapy efficacy and outcome for cancer patients, more representative and patient-specific preclinical models are needed. Organoids and tumoroids are 3D cell culture models that typically retain the genetic and epigenetic characteristics, as well as the morphology, of their tissue of origin. Thus, they can be used to understand the underlying mechanisms of cancer initiation, progression, and metastasis in a more physiological setting. Additionally, co-culture methods of tumoroids and cancer-associated cells can help to understand the interplay between a tumor and its tumor microenvironment. In recent years, tumoroids have already helped to refine treatments and to identify new targets for cancer therapy. Advanced culturing systems such as chip-based fluidic devices and bioprinting methods in combination with tumoroids have been used for high-throughput applications for personalized medicine. Even though organoid and tumoroid models are complex in vitro systems, validation of results in vivo is still the common practice. Here, we describe how both animal- and human-derived tumoroids have helped to identify novel vulnerabilities for cancer treatment in recent years, and how they are currently used for precision medicine., (© 2024. The Author(s).)

Simple Summary: Mutations of the DMD gene, encoding dystrophins, cause Duchenne muscular dystrophy (DMD). We found that while DMD transcription occurs throughout a spectrum of normal tissues, it is frequently downregulated across various malignancies. The molecular signature associated with this downregulation matches transcriptomic changes found in Duchenne muscles, even though most of these malignancies originate from tissues never previously associated with dystrophin expression or function. Importantly, we found that reduced DMD expression across different tumors was associated with reduced patients' survival and higher tumor stage. These findings call for re-evaluation of the current view that dystrophin expression found across numerous tissues is the result of an "illegitimate transcription" and demonstrate that the significance of this gene goes beyond its known involvement in Duchenne muscular dystrophy. Moreover, these data unite and explain the growing evidence that the DMD gene has a role in tumors. Altered dystrophin expression was found in some tumors and recent studies identified a developmental onset of Duchenne muscular dystrophy (DMD). Given that embryogenesis and carcinogenesis share many mechanisms, we analyzed a broad spectrum of tumors to establish whether dystrophin alteration evokes related outcomes. Transcriptomic, proteomic, and mutation datasets from fifty tumor tissues and matching controls (10,894 samples) and 140 corresponding tumor cell lines were analyzed. Interestingly, dystrophin transcripts and protein expression were found widespread across healthy tissues and at housekeeping gene levels. In 80% of tumors, DMD expression was reduced due to transcriptional downregulation and not somatic mutations. The full-length transcript encoding Dp427 was decreased in 68% of tumors, while Dp71 variants showed variability of expression. Notably, low expression of dystrophins was associated with a more advanced stage, older age of onset, and reduced survival across different tumors. Hierarchical clustering analysis of DMD transcripts distinguished malignant from control tissues. Transcriptomes of primary tumors and tumor cell lines with low DMD expression showed enrichment of specific pathways in the differentially expressed genes. Pathways consistently identified: ECM-receptor interaction, calcium signaling, and PI3K-Akt are also altered in DMD muscle. Therefore, the importance of this largest known gene extends beyond its roles identified in DMD, and certainly into oncology. [ABSTRACT FROM AUTHOR]

In designing porous scaffolds, permeability is essential to consider as a function of cell migration and bone tissue regeneration. Good permeability has been achieved by mimicking the complexity of natural cancellous bone. In this study, a porous scaffold was developed according to the morphological indices of cancellous bone (porosity, specific surface area, thickness, and tortuosity). The computational fluid dynamics method analyzes the fluid flow through the scaffold. The permeability values of natural cancellous bone and three types of scaffolds (cubic, octahedron pillar, and Schoen's gyroid) were compared. The results showed that the permeability of the Negative Schwarz Primitive (NSP) scaffold model was similar to that of natural cancellous bone, which was in the range of 2.0 × 10−11 m2 to 4.0 × 10−10 m2. In addition, it was observed that the tortuosity parameter significantly affected the scaffold's permeability and shear stress values. The tortuosity value of the NSP scaffold was in the range of 1.5–2.8. Therefore, tortuosity can be manipulated by changing the curvature of the surface scaffold radius to obtain a superior bone tissue engineering construction supporting cell migration and tissue regeneration. This parameter should be considered when making new scaffolds, such as our NSP. Such efforts will produce a scaffold architecturally and functionally close to the natural cancellous bone, as demonstrated in this study. [ABSTRACT FROM AUTHOR]

Two sodium vanadium phosphates, synthetic analogues of the minerals kosnarite, Na3V2(PO4)3, and yurmarinite, Na7V4(PO4)6, were obtained by hydrothermal synthesis simulating a natural hydrothermal solution. While the Na3V2(PO4)3 phase belongs to the NASICON family and is well-known for its high-ionic conductivity, the new Na7V4(PO4)6 compound is a rare case of V2+-containing oxosalts, which are hard to prepare due to their instability in air. Here we report the crystal structure of heterovalent vanadium phosphate studied by single crystal X-ray diffraction, XANES spectroscopy, and topological ion migration modelling. A discussion of divalent vanadium compounds of both natural and synthetic origin is also given, with a review of the methods for their synthesis and a comparative analysis of V–O bond lengths. [ABSTRACT FROM AUTHOR]

Large bone defects resulting from trauma, infection and tumors are usually difficult for the body's repair mechanisms to heal spontaneously. Generally, various types of bones and orthopedic implants are adopted to enhance bone repair and regeneration in the clinic. Due to the limitations of traditional treatments, bone defect repair is still a compelling challenge for orthopedic surgeons. In recent years, bone tissue engineering has become a potential option for bone repair and regeneration. Amidst the various scaffolds for bone tissue engineering applications, hydrogels are considered a new type of non-toxic, non-irritating and biocompatible materials, which are widely used in the biomedicine field currently. Some studies have demonstrated that hydrogels can provide a three-dimensional network structure similar to a natural extracellular matrix for tissue regeneration and can be used to transport cells, biofactors, nutrients and drugs. Therefore, hydrogels may have the potential to be multifunctional sustained-release drug carriers in the treatment of bone defects. The recent applications of different types of hydrogels in bone defect repair were briefly reviewed in this paper. [ABSTRACT FROM AUTHOR]

Background and Objectives: The majority of research on the effects of osteoporosis drugs has measured the bone mineral density (BMD) of the spine and femur through dual-energy X-ray absorptiometry (DEXA) and compared and analyzed the effects of the drugs through changes in the BMD values. This study aims to compare osteoclast and sclerostin expression in osteocytes after risedronate therapy by obtaining femoral heads from patients with hip fractures. Materials and Methods: We obtained the femoral heads of 10 female patients (age: ≥65 years) who received risedronate therapy for at least 1 year through hip arthroplasty during 2019–2021 (risedronate group). Meanwhile, 10 patients who had never received osteoporosis treatment were selected as controls using propensity scores with age, body mass index, and bone density as covariates (control group). While the osteoclast count was evaluated using tartrate-resistant acid phosphatase (TRAP) staining, the sclerostin expression in osteocytes was assessed using immunohistochemistry. Moreover, Western blotting and polymerase chain reaction (PCR) were performed for receptor activation of nuclear factor kappa-Β ligand (RANKL), RANK, osteoprotegerin (OPG), sclerostin, and bone morphogenetic protein-2 (BMP2). Results: TRAP staining revealed significantly more TRAP-positive cells in the control group (131.75 ± 27.16/mm2) than in the risedronate group (28.00 ± 8.12/mm2). Moreover, sclerostin-positive osteocytes were expressed more in the control group (364.12 ± 28.12/mm2) than in the risedronate group (106.93 ± 12.85/mm2). Western blotting revealed that the expressions of RANKL, RANK, sclerostin, and BMP2 were higher in the control group than in the risedronate group (p < 0.05). Furthermore, RANK, sclerostin, and OPG protein levels were higher in the control group than in the risedronate group. Conclusions: In this study, the risedronate group demonstrated lower osteoclast activity and sclerostin expression in osteocytes in the femoral head than the control group. [ABSTRACT FROM AUTHOR]

When designing scaffolds for bone tissue engineering (BTE), the wall shear stress (WSS), due to the fluid flow inside the scaffold, is an important factor to consider as it influences the cellular process involved in new tissue formation. The present work analyzed the average WSS in Schwartz diamond (SD) and gyroid (SG) scaffolds with different surface topologies and mesh elements using computational fluid dynamics (CFD) analysis. It was found that scaffold meshes with a smooth surface topology with tetrahedral elements had WSS levels 35% higher than the equivalent scaffold with a non-smooth surface topology with hexahedral elements. The present work also investigated the possibility of implementing the optimization algorithm simulated annealing to aid in the design of BTE scaffolds with a specific average WSS, with the outputs showing that the algorithm was able to reach WSS levels in the vicinity of 5 mPa (physiological range) within the established limit of 100 iterations. This proved the efficacy of combining CFD and optimization methods in the design of BTE scaffolds. [ABSTRACT FROM AUTHOR]

Naegleria fowleri, also known as the "brain-eating" amoeba, is a free-living protozoan that resides in freshwater bodies. This pathogenic amoeba infects humans as a casual event when swimming in contaminated water. Upon inhalation, N. fowleri invades the central nervous system and causes primary amoebic meningoencephalitis (PAM), a rapidly progressive and often fatal disease. Although PAM is considered rare, reducing its case fatality rate compels the search for pathogen-specific proteins with a structure–function relationship that favors their application as targets for discovering new or improved drugs against N. fowleri infections. Herein, we report a computational approach to study the structural features of Nf314 (a serine carboxypeptidase that is a virulence-related protein in N. fowleri infections) and assess its potential as a drug target, using bioinformatics tools and in silico molecular docking experiments. Our findings suggest that Nf314 has a ligand binding site suitable for the structure-based design of specific inhibitors. This study represents a further step toward postulating a reliable therapeutic target to treat PAM with drugs specifically aimed at blocking the pathogen proliferation by inhibiting protein function. [ABSTRACT FROM AUTHOR]

Body fluids are constantly replenished with a population of genetically diverse cell-free DNA (cfDNA) fragments, representing a vast reservoir of information reflecting real-time changes in the host and metagenome. As many body fluids can be collected non-invasively in a one-off and serial fashion, this reservoir can be tapped to develop assays for the diagnosis, prognosis, and monitoring of wide-ranging pathologies, such as solid tumors, fetal genetic abnormalities, rejected organ transplants, infections, and potentially many others. The translation of cfDNA research into useful clinical tests is gaining momentum, with recent progress being driven by rapidly evolving preanalytical and analytical procedures, integrated bioinformatics, and machine learning algorithms. Yet, despite these spectacular advances, cfDNA remains a very challenging analyte due to its immense heterogeneity and fluctuation in vivo. It is increasingly recognized that high-fidelity reconstruction of the information stored in cfDNA, and in turn the development of tests that are fit for clinical roll-out, requires a much deeper understanding of both the physico-chemical features of cfDNA and the biological, physiological, lifestyle, and environmental factors that modulate it. This is a daunting task, but with significant upsides. In this review we showed how expanded knowledge on cfDNA biology and faithful reverse-engineering of cfDNA samples promises to (i) augment the sensitivity and specificity of existing cfDNA assays; (ii) expand the repertoire of disease-specific cfDNA markers, thereby leading to the development of increasingly powerful assays; (iii) reshape personal molecular medicine; and (iv) have an unprecedented impact on genetics research. [ABSTRACT FROM AUTHOR]

Improving photophysical properties of poly[2-methoxy-5-(3,7-dimethyl-octyloxy)-1,4-phenylenevinylene]-end capped with dimethylphenyl, MDMO-PPV-DMP, was achieved via incorporation anatase titania nanoparticles (TiO2 NPs). Various contents of TiO2 NPs (up to 50 wt%) were dispersed into fixed concentration of the MDMO-PPV-DMP (5 mg/mL) via solution blending method followed by spin coating onto cleaned glass substrates to form their thin films. The formation of MDMO-PPV-DMP/TiO2 nanocomposites was evidenced from the results of X-ray diffractograms and Fourier transform infrared spectra, while the homogeneity of the films was detected by field emission-scanning electron microscopy (FE-SEM). Increasing the contents of TiO2 NPs resulted in a slight decrease (up to ~ 0.07 eV) in both direct and indirect energy band gaps of the MDMO-PPV-DMP in the nanocomposite thin films. A higher degree of disorder in the electronic structure of the MDMO-PPV-DMP/TiO2 nanocomposite and increasing the localized states density within the forbidden gap can be achieved by increasing the energy tail values and decreasing the steepness parameter with rising the TiO2 NPs content. The enhancement in emission intensity and broadening of emission spectra with increasing the TiO2 NPs content can be explained by the charge trapping effect and particle size distribution, respectively. Moreover, the incorporation of TiO2 NPs into the MDMO-PPV-DMP led to tuning its emitted light color which is of distinct interest in optoelectronic devices. [ABSTRACT FROM AUTHOR]

Strictures and abdominal pain often complicate Crohn's disease (CD). The primary aim was to explore whether parameters obtained by preoperative contrast-enhanced (CE) ultrasonography (US) and dynamic CE MR Enterography (DCE-MRE) of strictures associates with biomechanical properties. CD patients undergoing elective small intestinal surgery were preoperatively examined with DCE-MRE and CEUS. The excised intestine was distended utilizing a pressure bag. Luminal and outer bowel wall cross-sectional areas were measured with US. The circumferential stricture stiffness (Young's modulus E) was computed. Stiffness was associated with the initial slope of enhancement on DCE-MRE (ρ = 0.63, p = 0.007), reflecting active disease, but lacked association with CEUS parameters. For structural imaging parameters, inflammation and stricture stiffness were associated with prestenotic dilatation on US (τb = 0.43, p = 0.02) but not with MRE (τb = 0.01, p = 1.0). Strictures identified by US were stiffer, 16.8 (14.0–20.1) kPa, than those graded as no or uncertain strictures, 12.6 (10.5–15.1) kPa, p = 0.02. MRE global score (activity) was associated with E (ρ = 0.55, p = 0.018). Elastography did not correlate with circumferential stiffness. We conclude that increasing activity defined by the initial slope of enhancement on DCE-MRE and MRE global score were associated with stricture stiffness. Prestenotic dilatation on US could be a potential biomarker of CD small intestinal stricture stiffness. [ABSTRACT FROM AUTHOR]

Here, we investigate the shell shape variation of some closely related freshwater species of the bivalve genus Corbicula using descriptive (qualitative), geometric morphometric and traditional conchometric approaches. The combination of these different approaches allows for an effective discrimination between the species C. fluminalis, C. fluminea and C. leana , as well as an unidentified Corbicula sp. The roundness of the shell hinge is an important diagnostic feature, as are shell sculpture (ribs), symmetry of the apertural margin, and both position and extension of the umbo. We also identify possible hybrids between C. fluminalis and C. leana , with these showing features intermediate to those of the parent species. We examine variability of shell features of C. leana in selected areas in Europe and compare these results with material from the native range of Japan and Korea. For C. leana , we identify two geographic morphotypes from the native area; within Europe, there is a high morphological diversity of this species with several new forms arising, most probably as a result of hybridization. [ABSTRACT FROM AUTHOR]

External fixation is a commonly used method in stabilizing fracture sites. The performance of the fixator depends on how it affects the mechanical properties of the fracture site and is governed by parameters like the fixator type and fixator configuration. Identifying ideal configurations prior to surgery will help surgeons in planning the procedure, limiting the possibility of complications such as non-union. In this study, a framework has been proposed as a surgical pre-planning tool, to assist surgeons compare mechanical properties of a fracture site under different fixator configurations, and thereby identify the optimum solution. A computational tool was identified as the best method for this purpose. Cost and time of computation were given special consideration to reduce complexity in clinical settings. A pilot study was conducted on a section of the proposed framework, where the aim was to understand the feasibility of implementation. In the pilot study, a unilateral uni-planar fixator on a simple diaphyseal transverse fracture was analyzed. During the pilot study the selected fixator was tested and a few models were developed to assess system stability. The models were then compared to identify the optimum model that could be used with the proposed framework. The proposed framework provided a suitable solution for the use case and out of the models developed the simplified finite element model was identified as the best option for the use case. [ABSTRACT FROM AUTHOR]

Heuristically accelerated reinforcement learning (HARL) is a new family of algorithms that combines the advantages of reinforcement learning (RL) with the advantages of heuristic algorithms. To achieve this, the action selection strategy of the standard RL algorithm is modified to take into account a heuristic running in parallel with the RL process. This paper presents two approximated HARL algorithms that make use of pheromone trails to improve the behaviour of linearly approximated SARSA(λ ) by dynamically learning a heuristic function through the pheromone trails. The proposed dynamic algorithms are evaluated in comparison to linearly approximated SARSA(λ ), and heuristically accelerated SARSA(λ ) using a static heuristic in three benchmark scenarios: the mountain car, the mountain car 3D and the maze scenarios. [ABSTRACT FROM AUTHOR]

Interaction between a zinc porphyrin (ZnPor) as the end-group and poly(9,9-di-n-octylfluorene-2,7-vinylene) (PFV) as the main chain in a porphyrin end-modified fluorescent conjugated polymer, ZnPFV, was studied by time-resolved electron paramagnetic resonance (EPR) and fluorescence spectroscopy. While fluorescence from the PFV part of ZnPFV showed a spectral profile almost identical to that of a PFV oligomer without end-modification, the emission spectrum of the ZnPor part exhibited a much broader profile compared to that of the reference zinc porphyrin monomer. Based on the analysis of lifetimes and quantum yields, it was found that radiative rate constant of the ZnPor part was enhanced by nearly three times. The observed unusual enhancement in the radiative rate constant was rationalised in terms of a partial π-conjugation between the end group and the main chain, as a result of co-planarisation in fluid solution. On the other hand, the time-resolved EPR spectrum of ZnPFV at 100 K basically showed a similar spectral pattern to that of the reference zinc porphyrin, but with significant differences in zero-field spitting parameters and initial population ratios. The π-system of the excited triplet state is deduced to deviate from D4h symmetry in the end zinc porphyrin groups. The obtained results show that interaction of the porphyrin end group with the main chain of the polymer significantly influences the excited singlet state properties of the porphyrin, while its triplet state properties were affected to a lesser extent. [ABSTRACT FROM AUTHOR]

Leptotina butterflies (Lycaenidae, Polyommatiinae) are found mostly in tropical and subtropical areas around the globe, marginally penetrating into temperate regions. Here, we investigated phylogenetic and biogeographical relationships of most representatives of the subtribe, using both likelihood and Bayesian approaches. We also estimated the timing of their diversification. And lastly, we studied phylogeographic patterns of the most widespread species, Leptotes pirithous. DNA sequences from two mitochondrial (COI, COII) and two nuclear genes (wingless, Ef1α) were analysed for 13 species of the genus Leptotes Scudder and one species of the genus Cyclyrius Butler. Both genera together form a monophyletic clade, and Cyclyrius is rooted deep inside Leptotes. Therefore, we designate Cyclyrius to be a junior synonym of Leptotes. According to our study, the genus Leptotes originated between the late Eocene and early Oligocene (35–31 Ma). During the Miocene it dispersed to the rest of the southern hemisphere, with further speciation events within the Indo‐Australian region, and separate radiations in the Americas and the Afrotropics. Leptotes webbianus from the Canary Islands turned out to be sister to the American clade from which it split c. 12 Ma. Leptotes pirithous originated in Madagascar c. 4 Ma and invaded the whole of Africa and southern Europe, including numerous surrounding islands. Populations of L. pirithous from Mauritius and Madagascar turned out to represent a distinct species (Leptotes durrellisp.n.) and the same applies to the Australasian populations of Leptotes plinius (Leptotes lybasstat. rev.). This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:pub:20308930‐988B‐4327‐A35F‐CC983D46263B. [ABSTRACT FROM AUTHOR]

The Winter Colloquium on the Physics of Quantum Electronics (PQE) has been a seminal force in quantum optics and related areas since 1971. It is rather mind-boggling to recognize how the concepts presented at these conferences have transformed scientific understanding and human society. In January 2017, the participants of PQE were asked to consider the equally important prospects for the future, and to formulate a set of questions representing some of the greatest aspirations in this broad field. The result is this multi-authored paper, in which many of the world’s leading experts address the following fundamental questions: (1) What is the future of gravitational wave astronomy? (2) Are there new quantum phases of matter away from equilibrium that can be found and exploited - such as the time crystal? (3) Quantum theory in uncharted territory: What can we learn? (4) What are the ultimate limits for laser photon energies? (5) What are the ultimate limits to temporal, spatial and optical resolution? (6) What novel roles will atoms play in technology? (7) What applications lie ahead for nitrogen-vacancy centres in diamond? (8) What is the future of quantum coherence, squeezing and entanglement for enhanced super-resolution and sensing? (9) How can we solve (some of) humanity’s biggest problems through new quantum technologies? (10) What new understanding of materials and biological molecules will result from their dynamical characterization with free-electron lasers? (11) What new technologies and fundamental discoveries might quantum optics achieve by the end of this century? (12) What novel topological structures can be created and employed in quantum optics? [ABSTRACT FROM AUTHOR]

Two heat treatments were carried out below (Ti6Al4V800) and above (Ti6Al4V1050) Ti6Al4V beta-phase transformation temperature (980 °C), with the purpose of studying the effect of microstructure on the adhesion and proliferation of fibroblast cells, as well as their electrochemical behavior. These alloys were seeded with 10,000 L929 fibroblast cells and immersed for 7 days in the cell culture at 37 °C, pH 7.40, 5% CO2 and 100% relative humidity. Cell adhesion was characterized by Scanning Electron Microscopy (SEM) and Electrochemical Impedance Spectroscopy (EIS) techniques. Polygonal and elongated cell morphology was observed independent of Ti6Al4V microstructure. Besides, C, O, P, S, Na and Cl signals were detected by Energy Dispersive X-Ray Spectroscopy (EDX), associated with the synthesis of organic compounds excreted by the cells, including protein adsorption from the medium. In certain areas on Ti6Al4V and Ti6Al4V800 alloys, cells were agglomerated (island type), likely related to the globular microstructure; meanwhile, larger cellular coverage is shown for Ti6Al4V1050 alloy, forming more than one layer on the surface, where only Ca was recorded. Impedance diagrams showed a similar passive behavior for the different Ti6Al4V alloys, mainly due to TiO2 overlaying the contribution of the organic compounds excreted by fibroblast cells. [ABSTRACT FROM AUTHOR]

Background: ARID1A is an essential subunit of SWI/SNF chromatin remodeling complexes. ARID1A gene mutations and loss of ARID1A expression have been observed in a variety of cancers, and to be correlated with invasion, immune escape and synthetic lethality. As yet, however, the biological effect of ARID1A expression and its role in the prognosis of lung adenocarcinoma (LUAD) patients have remained unclear. In this study we aimed to further elucidate the role of ARID1A expression in LUAD in vitro and in vivo and to assess its effect on the clinical prognosis of LUAD patients., Methods: ARID1A expression was detected by IHC in tissue samples from LUAD patients. After regular culturing of LUAD cell lines and constructing stable ARID1A knockdown lines, wound healing and Transwell assays were used to assess the role of ARID1A in cell migration and invasion. The effect of ARID1A knockdown on metastasis was verified in vivo. Western blotting was used to examine the expression of target proteins. Univariate and multivariate analyses were performed to assess survival and to provide variables for nomogram construction. In addition, we used the "rms" package to construct a prognostic nomogram based on a Cox regression model., Results: We found that ARID1A expression serves as an effective prognostic marker for LUAD patients. Loss of ARID1A expression correlated with a poor prognosis, as verified with a nomogram based on a Cox regression model. In addition, we found that ARID1A knockdown promoted LUAD cell proliferation, migration and invasion in vitro and enhanced LUAD metastasis in vivo by activating the Akt signaling pathway., Conclusions: Our data indicate that loss of ARID1A expression promotes LUAD metastasis and predicts a poor prognosis in LUAD patients., (© 2021. Springer Nature Switzerland AG.)

The mycalesine butterfly genus Heteropsis Westwood, 1850 (Satyrinae: Mycalesina) has recently been conceived to be represented in three major palaeotropical regions (Madagascar, Africa and Asia), but there has been no formal taxonomic treatment covering this entire group. Studies aimed at understanding the evolutionary success of Mycalesina in the Old World tropics have been hampered by the lack of both a robust phylogeny and a stable nomenclature for this satyrine subtribe. Here, we present a well-supported molecular phylogeny based on 10 genes and 133 exemplar taxa, representing almost all known species groups of Heteropsis (s.l.), and including all but four known species in Madagascar. We also combine sequences of the exemplars with a morphological matrix of 428 characters. The widespread ' Heteropsis clade' is confirmed as monophyletic, but lineages in different geographic regions also form endemic and well-supported clades with deep divergences among them. Here we establish this group as comprising three genera, Heteropsis (Malagasy region only), Telinga Moore, 1880 (Asia), and Brakefieldia gen.n. (Africa). We recover the genera Telinga and Brakefieldia as sisters with high support. Each genus is taxonomically characterized and a revised synonymic checklist is appended with new combinations and some changes in rank. With a well-resolved topology and updates to the taxonomy of the group, researchers are now in a position to explore the drivers of the spectacular radiation of the group, notably in Madagascar, where the highest phenotypic and species diversity occurs. This published work has been registered in ZooBank, . [ABSTRACT FROM AUTHOR]

Male genitalia are among the most rapidly evolving and divergent morphological structures and sexual selection is known to drive this phenomenon in many taxa. Because of their diversity, even within a single genus, genital characters are frequently used to infer relationships among closely-related species. Moths within the genus Izatha (Xyloryctidae) are ideal candidates for investigating the phylogenetic patterns of genital evolution as they display great variation in male genital structure and complexity. We determined the evolutionary relationships among 31 species of Izatha by constructing a molecular phylogeny of the genus based on the mitochondrial cytochrome oxidase subunit I gene and the isocitrate dehydrogenase and carbamoylphosphate synthase domain protein nuclear genes. This allowed estimations of ancestral male genital character states and patterns of male genital diversification using maximum-likelihood models. The genus is divided into two well-supported clades and two poorly supported clades at the root of the phylogeny with incomplete phylogenetic resolution within two species groups, likely due to rapid speciation. Izatha display a number of apomorphic phallic traits including cornuti (sclerotized spines) which are either discharged into the female during copulation (deciduous cornuti) or fixed to the male phallus (compound and fish-hook cornuti). Within the genus, there is a reduction of secondary genital characters - the uncus and gnathos - but an elaboration of another grasping structure, the juxta; the potential origin and functionality of these male genital traits are discussed. Overall, some male genital characters provided a good indication of species relationships; however, several parts of the complex male genitalia of Izatha show evidence of homoplasy and convergence highlighting the problems of using these traits in determining species relationships. Additionally, this convergence has highlighted that complex genital structures may evolve repeatedly and independently within a lineage. [ABSTRACT FROM AUTHOR]

This study aimed to define progesterone 5β-reductases (P5βR, EC 1.3.99.6, enone 1,4-reductases) as function-associated molecular markers at the plant family level. Therefore cDNAs were isolated from 25 Brassicaceae species, including two species, Erysimum crepidifolium and Draba aizoides, known to produce cardiac glycosides. The sequences were used in a molecular phylogeny study. The cladogram created is congruent to the existing molecular analyses. Recombinant His-tagged forms of the P5β R cDNAs from Aethionema grandiflorum, Draba aizoides, Nasturtium officinale, Raphanus sativus and Sisymbrium officinale were expressed in E. coli. Enone 1,4-reductase activity was demonstrated in vitro using progesterone and 2-cyclohexen-1-one as substrates. Evidence is provided that functional P5βRs are ubiquitous in the Brassicaceae. The recombinant P5βR enzymes showed different substrate preferences towards progesterone and 2-cyclohexen-1-one. Sequence comparison of the catalytic pocket of the P5βR enzymes and homology modelling using Digitalis lanata P5βR ( PDB ID: 2V6G) as template highlighted the importance of the hydrophobicity of the binding pocket for substrate discrimination. It is concluded that P5β R genes or P5βR proteins can be used as valuable function-associated molecular markers to infer taxonomic relationship and evolutionary diversification from a metabolic/catalytic perspective. [ABSTRACT FROM AUTHOR]

Poor diet quality frequently constrains the growth and reproduction of primary consumers, altering their population dynamics, interactions in food webs, and contributions to ecosystem services such as nutrient cycling. The identification and measurement of an animal's nutritional state are thus central to studying the connections between diet and animal ecology. Here we show how the nutritional state of a freshwater invertebrate, Daphnia magna, can be determined by analyzing its endogenous metabolites using hydrogen nuclear magnetic resonance-based metabolomics. With a multivariate analysis, we observed the differentiation of the metabolite composition of animals grown under control conditions (good food and no environmental stress), raised on different diets (low quantity, nitrogen limited, and phosphorus limited), and exposed to two common environmental stressors (bacterial infection and salt stress). We identified 18 metabolites that were significantly different between control animals and at least one limiting food type or environmental stressor. The unique metabolite responses of animals caused by inadequate nutrition and environmental stress are reflective of dramatic and distinctive effects that each stressor has on animal metabolism. Our results suggest that dietary-specific induced changes in metabolite composition of animal consumers hold considerable promise as indicators of nutritional stress and will be invaluable to future studies of animal nutrition. [ABSTRACT FROM AUTHOR]