Browse Articles

Development of a tissue-specific bioscaffold for intestinal stem cell culture

The generation of a tissue-specific intestinal hydrogel derived from the native intestine has the potential to support and promote the growth of intestinal organoids. In this study, we aimed to develop hydrogels derived exclusively from intestinal extracellular matrix (ECM) or composites comprised of intestinal ECM combined with alginate that allow for greater tuning of the hydrogel properties. A novel mouse intestinal decellularization protocol was developed and the ECM characterized. Our analyses demonstrate that our protocol effectively removed cellular and nuclear content while preserving key ECM components including collagens, glycosaminoglycans, fibronectin and laminin. When the decellularized small intestine (DSI) was used to generate hydrogels, the resulting ECM showed bioactivity as demonstrated by metabolic and pro-proliferative effects on NIH 3T3 murine fibroblasts. Importantly, our novel DSI hydrogels also supported murine intestinal and colonic organoid growth similar to Matrigel® controls. These studies demonstrate that murine tissue-specific DSI hydrogels can provide a supportive environment for the culture of intestinal and colonic organoids in vitro.

Total Synthesis of Paxdaphnine A and Daphlongamine B via an Aza-Prins Cyclization Strategy

Assessment of methods for evaluating structural stability of cell envelope fragments in hypersaline brines as biosignatures of ancient microbial life

Abstract The study of biomolecular stability of proteins and lipids in extreme saline environments is critical for understanding the preservation of potential microbial biosignatures of ancient life on Earth and other planetary bodies, including Mars. In this study, we evaluate the compatibility of several analytical techniques, Nano-Differential Scanning Fluorometry (NanoDSF), Analytical Ultracentrifugation (AUC), and Differential Scanning Calorimetry (DSC) with hypersaline brine analogues of Early Earth and Early Mars conditions. Using the halophilic archaeon Halobacterium salinarum as a model, we examine the structural stability of proteins within cell envelope fragments from dead cells, focusing on their preservation potential in complex brines. The results reveal significant technical challenges in studying macromolecules in high-salinity environments, including crystallisation during DSC and NanoDSF, viscosity-related artifacts in AUC, and reduced fluorescence signals in NanoDSF due to the low tryptophan content of membrane proteins from halophilic archaea. Nevertheless, NanoDSF proved useful for analysing multi-protein systems and DSC may be applicable using new generation technology, while AUC showed limited applicability under extreme saline conditions. These findings provide crucial insights into the methodologies for studying the stability of halophilic biomolecules in brine environments and the limitations of current techniques in extreme settings.

ProProtein: A platform for fully automated identification of 3D structure fluctuations in MD simulation trajectories

The main goal of Molecular Dynamics (MD) is a simulation of a physical system motions in a fixed time period. This technique allows users to observe the dynamic evolution of the system but requires advanced force fields and is computationally intensive. Furthermore, finding desirable features in the results obtained is usually a time-consuming task. This motivates the need to implement a tool that visualizes the most flexible protein fragments. ProProtein platform is a sophisticated web server where, with a single click, the user can set up, configure, and run an MD simulation of the 3D structure of the peptide/protein. We perform the simulation using an open-source software suite developed for high-performance molecular dynamics named Gromacs. The resulting MD trajectory is then automatically analyzed within the dedicated heuristic algorithm to identify 3D fragments characterized by high instability in the context of the given (input) structure. These high-fluctuation substructures are presented next to the user with the Mol* package. They are visualized in colors on each frame covered by the considered trajectory. This tool can easily support the evaluation of the reliability of protein 3D structure predictions obtained computationally. The ProProtein platform is free and open to all users. It is publicly available at: https://proprotein.cs.put.poznan.pl/.

Flexible Double Bonds-Enhanced Photodynamic Therapy toward Antibacterial Resistance

Experimental and numerical investigation of suddenly expanded flow at sonic mach number

Quantification of H3.1-nucleosomes using a chemiluminescent immunoassay: A reliable method for neutrophil extracellular trap detection

Neutrophil extracellular traps (NETs) are chromatin-based web-like structures released by activated neutrophils in response to infectious agents. Overproduction or insufficient clearance of NETs contributes to dysfunction of immune response and disease pathogenesis, underlying the importance of early detection and monitoring of NET levels in clinical samples. While existing methods for NETs detection and quantification face limitations, there is a pressing need for a reliable, sensitive, and clinically applicable assay. Since NETs consist of long strains of decondensed chromatin, with nucleosomes as their basic units, we propose circulating H3.1-nucleosomes as biomarkers for NETs detection in clinical plasma samples. In the initial phase of our study, we confirmed the presence of H3.1-nucleosomes by immunofluorescence and immunoprecipitation experiments in two in vitro NET models: neutrophil-like cells differentiated from the HL-60 cell line, and primary neutrophils isolated from whole blood, both treated with either phorbol 12-myristate 13-acetate or calcium ionophore A23187 to induce NETs formation. Subsequently, we developed and analytically validated a chemiluminescent immunoassay for the quantification of circulating H3.1-nucleosomes in plasma. This fully automated assay demonstrates convincing analytical performance in parameters including sensitivity, precision, linearity and reproducibility. Overall, by measuring the H3.1-nucleosome levels in plasma samples from patients suffering from NETs-related diseases compared to healthy donors, we demonstrated the assay’s clinical value in identifying NETs-associated pathologies and its potential utility for disease management.

Ordering Bent and Straight Dicarboxylate Linkers in an fcu Zirconium Metal–Organic Framework

Grinding wheel wear evaluation with the PMSCNN model

RETRACTED: A 12,800-year-old layer with cometary dust, microspherules, and platinum anomaly recorded in multiple cores from Baffin Bay

The Younger Dryas Impact Hypothesis (YDIH) posits that ~12,800 years ago Earth encountered the debris stream of a disintegrating comet, triggering hemisphere-wide airbursts, atmospheric dust loading, and the deposition of a distinctive suite of extraterrestrial (ET) impact proxies at the Younger Dryas Boundary (YDB). Until now, evidence supporting this hypothesis has come only from terrestrial sediment and ice-core records. Here we report the first discovery of similar impact-related proxies in ocean sediments from four marine cores in Baffin Bay that span the YDB layer at water depths of 0.5–2.4 km, minimizing the potential for modern contamination. Using scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS) and laser ablation ICP-MS, we detect synchronous abundance peaks of metallic debris geochemically consistent with cometary dust, co-occurring with iron- and silica-rich microspherules (4–163 μm) that are predominantly of terrestrial origin with minor (<2 wt%) ET contributions. These microspherules were likely formed by low-altitude touchdown airbursts and surface impacts of comet fragments and were widely dispersed. In addition, single-particle ICP-TOF-MS analysis reveals nanoparticles (<1 μm) enriched in platinum, iridium, nickel, and cobalt. Similar platinum-group element anomalies at the YDB have been documented at dozens of sites worldwide, strongly suggesting an ET source. Collectively, these findings provide robust support for the YDIH. The impact event likely triggered massive meltwater flooding, iceberg calving, and a temporary shutdown of thermohaline circulation, contributing to abrupt Younger Dryas cooling. Our identification of a YDB impact layer in deep marine sediments underscores the potential of oceanic records to broaden our understanding of this catastrophic event and its climatological impacts.

Size-dependent static response of a functionally graded nanobeam attached to a piezoelectric fibre-reinforced composite actuator

Spectrum of urolith composition among a multi-ethnic population at the Aga Khan hospital, Dar-es-Salaam, Tanzania

Background Urolithiasis is among the commonest diseases affecting the urinary tract with worldwide prevalence varying from 1%−20%. A urolith refers to a calculus or stone within the urinary tract, knowledge of urolith composition is important in understanding their etiology, treatment and preventing recurrence. This study aimed to describe the spectrum of urolith compositions among patients seen at the Aga Khan Hospital Dar-es-Salaam, Tanzania. Methods This was a hospital based cross-sectional study carried out among patients with urolithiasis treated during a ten-year period from January 2011 to December 2020 whose stones were sent for stone analysis by infrared spectroscopy. Data on age, sex, clinical presentation, mode of diagnosis, mode of extraction and chemical composition was analyzed. Results A total of 168 adult patients were included in the study, with a mean age of 44.7 yrs. (SD 10.99). Males (83.3%) were more affected than females. The majority (58.3%) of stones were found in the ureters. Purely calcium oxalate stones was the predominant composition of urinary tract stones, found in 66.1% of patients, this predominance was observed across both genders and across all age groups and anatomical locations, following calcium oxalate only stones in prevalence were stones with mixed calcium oxalate and calcium phosphate (21.4%). Conclusion Stones in our setting were of mixed composition. The most common constituent of stones across all ages, gender and locations was calcium oxalate only stones. Male gender was most predominant and the commonest site of urinary calculi was the ureters.

Specific Ion Properties Induce Spontaneous H₂O₂ Production at the Air–Water Interface

Assessing induced abortion underreporting in restrictive settings using prospective morbidity surveys from Kenya, Liberia, and Sierra Leone

Prevalence and associated factors of overweight and obesity among reproductive-aged women (15–49 years) in Ratnanagar Municipality, Chitwan district, Nepal

Background Overweight and obesity is a rising public health threat both in developed and developing countries including Nepal. Nepal is undergoing rapid urbanization, accompanied by significant changes in lifestyle, dietary practices, and behavioral patterns. This shift has contributed to a rising prevalence of overweight and obesity. This study aimed to determine the prevalence of overweight and obesity and their associated factors among reproductive-aged women of Ratnanagar Municipality (RM), Chitwan. Methodology A cross-sectional study was conducted in selected wards of Ratnanagar Municipality, Chitwan district. A multistage sampling method was followed for the selection of participants. Face-to-face interview was conducted using a structured questionnaire. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 25.0 (IBM). Descriptive results were presented using the frequencies, percentages, mean, and standard deviation. Bivariate analysis was performed using Chi-square and bivariate binary logistic regression. The factors associated with the prevalence of overweight and obesity were determined using a multivariate logistic regression analysis. All the tests were performed at a 95% Confidence Interval and variables with p-values less than 0.05 were considered statistically significant. Results A total of 318 individuals participated in this study. More than half of the participants (51.6%) were overweight/obese. This study demonstrated that participant’s socio-demographic and behavioral characteristics such as age (AOR = 3.3, CI: 1.5–4.4), ethnicity (AOR = 2.3, CI:1.2–4.3), higher education (AOR = 2.6 CI:1.8–5.8), family type (AOR = 0.4, CI:0.1–0.8) and moderate physical activity (AOR = 3.0, CI: 1.2–7.4) were statistically significant with the prevalence of overweight and obesity. Conclusion This study concludes a significant burden of overweight and obesity (51.6%) among reproductive-aged women, with socio-demographic, lifestyle, and behavioral factors playing a key role. Factors such as age, education, occupation, and physical activity were linked to overweight and obesity. The findings highlight the need for targeted interventions to combat obesity, emphasizing the importance of behavioral changes, public health awareness, and community-based campaigns to promote healthy eating, and reduced sedentary behavior.

C–H Amination of Arenes and Heteroarenes through a Dearomative (3 + 2) Cycloaddition

Predict the writer’s trait emotional intelligence from reproduced calligraphy

Personality traits and resilience mediated by depressive symptoms in a sample of psychotherapy patients: A cross-sectional study

Introduction Resilience is a concept that has been widely studied in different contexts and is related to adaptation to different stress levels. Although research in psychotherapy has produced vast knowledge about the effectiveness and mechanisms that mediate response, there is still no clarity about the role of resilience in this process, especially research in psychotherapy with patients with severe mental illness. Due to the implications of severe mental illness in different areas of life, in these patients, the capacity for resilience may be impaired, and the mechanisms involved in mediating this process are still not well explained. Objective Verify the associations between personality traits and resilience and their potential confounders (sociodemographic factors, pharmacological treatment, type of psychotherapy, social support, depressive and anxiety symptoms). Assess depressive symptoms as a possible mediator of the relationship between personality traits and resilience. Methods This is a naturalistic cross-sectional study, with 83 participants undergoing psychotherapy from different theoretical lines (psychodynamic, cognitive-behavioural, and interpersonal). Sociodemographic characteristics were evaluated, as well as resilience (25-item Connor Davidson Resilience Scale), depressive symptoms (Beck Depression Inventory), anxious symptoms (Beck Anxiety Inventory), and Personality traits (Personality Inventory for DSM-5). Results Resilience was negatively associated with depressive symptoms (B = −12.1, p < 0.001). The mediation effect was significant for depressive symptoms (b = −7.21, BCa 95% CI [−12.6, −3.07]). This variable mediated approximately 46% of the relationship between negative affectivity and resilience. Conclusion Resilience was positively associated with antagonism traits and negatively with negative affectivity and depressive symptoms. Depressive symptoms mediated 46% of the relationship between negative affectivity and resilience. The main findings of this study contribute to a greater understanding of the mechanisms involved in resilience, thus influencing the mental health outcomes of patients with severe mental illness.

Effect of a single ultra processed meal on myocardial endothelial function, adenosine mediated effects and cognitive performances

Efficacy of MRI and clinical findings of Lidocaine injection combined with manual therapy in frozen shoulder—A prospective, randomized, single-blinded, sham-controlled trial

Background Frozen shoulder, or adhesive capsulitis, is a debilitating condition characterized by progressive pain and restricted range of motion in the glenohumeral joint. A wide range of interventions has been explored for its management, including conservative physiotherapy approaches such as thermotherapy, manual therapy, and therapeutic exercises. Pharmacological interventions, including pain medications, and muscle relaxants are commonly employed to alleviate symptoms. Additionally, intra-articular corticosteroid injections have been shown to provide short-term relief. While each modality offers potential benefits, the optimal treatment strategy remains a subject of ongoing investigation. Purpose The objective of this study is to investigate the clinical and magnetic resonance image (MRI) changes after lidocaine injection with manual therapy in frozen shoulder. Study design/ setting Randomized, single-blinded controlled study conducted at University hospital. Patient sample Sixty eligible participants were divided into an active group (n = 30; Lidocaine injection with active manual therapy) and the placebo group (n = 30; Lidocaine injection with placebo manual therapy) 4 sessions per week for 4 weeks. Outcome measures The primary outcome was pain intensity, measured with the visual analogue scale and the other outcome measures were range of motion (ROM), functional disability, thickness of corocohumeral ligament (CHL) by MRI, and quality of life which was measured at baseline, after 4 weeks, 8 weeks and at 6 months. Results The VAS score at 4 weeks shows an improvement 2.4 (CI 95% 2.08 to 2.71) in the active group than the placebo group. Similar effects have been noted after 8 weeks 3.0 (CI95% 2.68 to 3.31) and at 6 months 2.5 (CI95% 2.18 to 2.81). Similar statistically significant improvements were found in the ROM (abduction & Lateral rotation), functional disability, thickness of CHL ligament, status and quality of life (p = 0.001). Conclusion Lidocaine injection with active manual therapy consists of scapula mobilization and posterior capsular stretching was superior to placebo group for improving pain, ROM, functional disability, and quality of life in people with frozen shoulder. Trial registration ClinicalTrials.gov CTRI/2020/04/024853