TAT-PBX1 Reverses Hyperglycemia Through β-Cell Regeneration and Functional Restoration in an STZ-Induced Diabetic Model
Xiangyuan Meng, Zhenhu Zhao, Xin Zhang
et al.
<b>Objective:</b> β-cell dysfunction and loss are major pathological determinants of impaired islet function and hyperglycemia in diabetes. Given the inability of current therapies to restore β-cell viability or glucose-responsive insulin secretion, this study aimed to investigate whether a cell-permeable PBX1 fusion protein (TAT-PBX1) could rescue streptozotocin (STZ)-induced β-cell injury and restore β-cell functional integrity. <b>Methods:</b> A TAT-PBX1 recombinant fusion protein was produced using a prokaryotic expression system. Its protective effects were assessed in STZ-treated MIN6 β cells and in a mouse model of STZ-induced diabetes, with the glucokinase (GK) activator dorzagliatin included as a positive control. We evaluated β-cell apoptosis, DNA damage, ATP and NAD<sup>+</sup>/NADH levels, insulin signaling (IRS1/PI3K/Akt), and the expression of PDX1 and GK. Glucose-stimulated insulin secretion (GSIS), glucose tolerance, islet morphology, and β-cell proliferation were also examined in vivo. <b>Results:</b> TAT-PBX1 was detectable and significantly enriched in pancreatic tissue and mitigated STZ-induced cytotoxicity by reducing DNA damage, PARP1-associated energy depletion, and β-cell apoptosis. It restored intracellular ATP and NAD<sup>+</sup>/NADH ratios and reactivated IRS1/PI3K/Akt signaling. TAT-PBX1 further enhanced PDX1 protein levels and upregulated GK, resulting in improved glucose uptake and GSIS. In addition, it increased Ki67<sup>+</sup> β-cell proliferation. In diabetic mice, TAT-PBX1 improved glucose tolerance, preserved islet morphology and number, and improved insulin signaling responsiveness. <b>Conclusions:</b> TAT-PBX1 restores β-cell function through coordinated protection of cellular metabolism and insulin signaling, leading to improved β-cell survival, glucose responsiveness, and regenerative capacity. These findings support TAT-PBX1 as a promising molecular strategy for β-cell-protective and β-cell-restorative diabetes therapy.
Medicine, Pharmacy and materia medica
Oral Side Effects of Isotretinoin Therapy in Acne Patients: A Prospective Study
Reem M. Alqahtani, R. S. Alatwi, M. Almohammed Jinan Mohammed
et al.
Background:
Isotretinoin is used to treat severe, disfiguring nodular acne. It is effective against acne vulgaris and its systemic adverse effects are documented, but there is limited research on oral side effects.
Aim:
The aim of this study was to evaluate the oral side effects associated with isotretinoin therapy in patients diagnosed with acne vulgaris. Particular attention was given to manifestations such as cheilitis, xerostomia, mucosal ulcerations, and gingival changes, as these may affect patient comfort and adherence to therapy.
Methodology:
A prospective study was conducted on 60 patients receiving oral isotretinoin. Comprehensive oral examinations were performed at baseline and repeated at regular intervals throughout the treatment period to monitor for the onset, type, and severity of oral adverse effects. Patient-reported symptoms were also recorded to complement clinical observations.
Results:
Cheilitis was the most frequently observed oral side effect, occurring in 45 patients (75%), followed by xerostomia in 30 patients (50%). Less frequent manifestations included mucosal ulcerations (16.7%) and gingival changes (13.3%). All adverse effects were generally mild to moderate in severity and were effectively managed with supportive care without interrupting therapy.
Conclusion:
Oral side effects of isotretinoin therapy are predictable, primarily mild to moderate, and manageable with appropriate care. Early recognition, preventive measures, and patient education can minimize discomfort and ensure adherence, allowing patients to safely benefit from the therapeutic effects of isotretinoin.
Pharmacy and materia medica, Analytical chemistry
Investigation into Safety Profiles of Antiepileptic Drugs and Identification of Predictors for Serious Adverse Events: Insights from National Pharmacovigilance Data
Soo Hyeon Lee, Dae Hyeon Sung, Euna Cho
et al.
<b>Backgrounds/Objectives:</b> This study aims to comprehensively characterize the prevalence and severity of antiepileptic drug (AED)-induced adverse drug events (ADEs) and to identify predictors strongly associated with serious adverse events (SAEs) in both general and geriatric populations. <b>Methods:</b> This cross-sectional study investigated AED-related ADEs reported to the KIDS KAERS DB from January 2014 to December 2023. Disproportionality analysis was performed to detect the association between reported SAEs, and multiple logistic regression was conducted to identify predictors associated with SAEs. Cox’s proportional hazard model was utilized to assess ADE duration in elderly patients aged 60 years and older. <b>Results:</b> More than 50% of 36,809 AED-related ADEs were reported in elderly patients aged 60 years and older, and the prevalence of SAEs was 3.78%. ADEs associated with endocrine disorders had the highest likelihood of SAEs being reported (ROR 15.30), followed by hematological disorders. The predictors associated with elevated SAE risks in the elderly were male sex (OR 1.91; 95% CI 1.62–2.27), aging (OR 1.17; 95% CI 1.04–1.31), and certain AEDs. However, the concomitant administration of acid-suppressive therapy (AST) and opioids was associated with a lower risk of SAEs in the elderly population. Elderly patients not receiving concomitant AST were less likely to experience prolonged ADE duration (HR 0.28, 95% CI 0.07–1.15); however, no substantial differences in ADE duration were observed with the concomitant use of opioids. <b>Conclusions:</b> This study implies significant variability in the frequency, severity, and duration of ADEs depending on the type of AEDs, patient demographics, and concomitant medication use.
Medicine, Pharmacy and materia medica
Pharmacokinetics of Pegaspargase with a Limited Sampling Strategy for Asparaginase Activity Monitoring in Children with Acute Lymphoblastic Leukemia
Cristina Matteo, Antonella Colombini, Marta Cancelliere
et al.
<b>Background</b>: Asparaginase (ASPase) plays an important role in the therapy of acute lymphoblastic leukemia (ALL). Serum ASPase activity (SAA) can be modified and even abolished by host immune responses; therefore, current treatment guidelines recommend to monitor SAA during treatment administration. The SAA monitoring schedule needs to be carefully planned to reduce the number of samples without hampering the possibility of measuring pharmacokinetics (PK) parameters in individual patients. Complex modelling approaches, not easily applicable in common practice, have been applied in previous studies to estimate ASPase PK parameters. This study aimed to estimate PK parameters by using a simplified approach suitable for real-world settings with limited sampling. <b>Methods</b>: Our study was based on 434 patients treated in Italy within the AIEOP-BFM ALL 2009 trial. During the induction phase, patients received two doses of pegylated ASPase and were monitored with blood sampling at five time points, including time 0. PK parameters were estimated by using the individually available SAA measurements with simple modifications of the classical non-compartmental PK analysis. We also took the opportunity to develop and validate a series of limited sampling models to predict ASPase exposure. <b>Results</b>: During the induction phase, average ASPase activity at day 7 was 1380 IU/L after the first dose and 1948 IU/L after the second dose; therapeutic SAA levels (>100 IU/L) were maintained until day 33 in 90.1% of patients. The average AUC and clearance were 46,937 IU/L × day and 0.114 L/day/m<sup>2</sup>, respectively. The database was analyzed for possible associations of PK parameters with biological characteristics of the patients, finding only a limited dependence on sex, age and risk score; however, these differences were not sufficient to allow any dose or schedule adjustments. Thereafter the possibility of further sampling reduction by using simple linear models to estimate the AUC was also explored. The most simple model required only two samplings 7 days after each ASPase dose, with the AUC being proportional to the sum of the two measured activities A(7) and A(21), calculated by the formula AUC = 14.1 × [A(7) + A(21)]. This model predicts the AUC with 6% average error and 35% maximum error compared to the AUC estimated with all available measures. <b>Conclusions</b>: Our study demonstrates the feasibility of a direct estimation of PK parameters in a real-life situation with limited and variable blood sampling schedules and also offers a simplified method and formulae easily applicable in clinical practice while maintaining a reliable pharmacokinetic monitoring.
Pharmacy and materia medica
Next-Generation Hydrogels for Biliary Organoid Engineering
Andrea Marfoglia, Giovanni Sorrentino
The biliary tree is a fundamental structural and functional component of the liver, lined with cholangiocytes which control bile flow and regulate bile homeostasis. In addition to their physiological roles, cholangiocytes are involved in pathological processes known as cholangiopathies. These biliary disorders significantly impair liver function, and their effects are often irreversible, making liver transplantation the only curative option. This substantial clinical burden highlights the need for innovative bioengineered strategies to study disease mechanisms and to restore or replace biliary tissue. In this framework, biliary organoids offer a robust platform to model liver diseases in vitro with physiological accuracy. Compared with traditional 2D or explant-based systems, organoids provide higher physiological relevance, patient specificity, and scalability, although challenges remain in standardization and clinical translation. Organoids are traditionally cultured within basement membrane extract (BME) matrices, which are commercially available under various names. While BME-based matrices support organoid growth and function, their undefined composition, variability, and animal origin limit reproducibility and clinical translation. These drawbacks have driven the development of alternative matrices based on engineered hydrogels. Hydrogels, whether of natural or synthetic origin, provide chemically defined and tunable environments that allow independent modulation of their biochemical and biophysical properties. Acting at the interface between materials science and biology, they enable the creation of microenvironments with precisely controlled cues. In this review, we summarize advances in biliary organoid bioengineering and discuss how hydrogel-based systems are shaping next-generation platforms for organoid growth, differentiation, and disease modeling toward more translationally relevant biliary models.
Medicine, Pharmacy and materia medica
Therapeutic Approaches with Iron Oxide Nanoparticles to Induce Ferroptosis and Overcome Radioresistance in Cancers
Dorianne Sant’Angelo, Géraldine Descamps, Valentin Lecomte
et al.
The emergence of nanotechnology in medicine, particularly using iron oxide nanoparticles (IONPs), may impact cancer treatment strategies. IONPs exhibit unique properties, such as superparamagnetism, biocompatibility, and ease of surface modification, making them ideal candidates for imaging, and therapeutic interventions. Their application in targeted drug delivery, especially with traditional chemotherapeutic agents like cisplatin, has shown potential in overcoming limitations such as low bioavailability and systemic toxicity of chemotherapies. Moreover, IONPs, by releasing iron ions, can induce ferroptosis, a form of iron-dependent cell death, which offers a promising pathway to reverse radio- and chemoresistance in cancer therapy. In particular, IONPs demonstrate significant potential as radiosensitisers, enhancing the effects of radiotherapy by promoting reactive oxygen species (ROS) generation, lipid peroxidation, and modulating the tumour microenvironment to stimulate antitumour immune responses. This review explores the multifunctional roles of IONPs in radiosensitisation through ferroptosis induction, highlighting their promise in advancing treatment for head and neck cancers. Additional research is crucial to fully addressing their potential in clinical settings, offering a novel approach to personalised cancer treatment.
Medicine, Pharmacy and materia medica
Optimized Hesperidin-Loaded Lipid Nanoparticles with Tea Tree Oil for Enhanced Wound Healing: Formulation, Characterization, and Evaluation
Borros Arneth, Rehab Abdelmonem, Mohamed A. El-Nabarawi
et al.
<b>Objectives:</b> This study aimed to develop hesperidin solid lipid nanoparticles (HESP-SLNs) to enhance their stability, solubility, and sustained release for wound healing; further enhancement was achieved through prepared nanostructured lipid carriers (HESP-NLCs) using Tea Tree Oil (TTO) to explore their synergistic efficacy. <b>Methods</b>: A factorial design of 2<sup>4</sup> trials was established to evaluate the influence of lipid type (X1), lipid conc (%) (X2), surfactant type (X3), and sonication amplitude (%) (X4) of prepared HESP-SLNs on the particle size (nm) (Y1), polydispersibility index (Y2), zeta potential (Y3), and encapsulation efficiency (%) (Y4). The optimized HESP-SLNs formula was selected utilizing Design Expert<sup>®</sup> software version 13, which was additionally enhanced by preparing TTO-loaded HESP-NLCs. In vitro release, Raman spectroscopy, and transmission electron microscopy were carried out for both lipid nanoparticles. Cytotoxicity, in vivo wound-healing assessments, and skin irritancy tests were performed to evaluate the performance of TTO-incorporated HESP-NLCs compared to HESP-SLNs. <b>Results:</b> The optimized formula demonstrated PS (280 ± 1.35 nm), ZP (−39.4 ± 0.92 mV), PDI (0.239 ± 0.012), and EE% (88.2 ± 2.09%). NLCs enhanced Q6% release, (95.14%) vs. (79.69%), for SLNs and showed superior antimicrobial efficacy. Both lipid nanoparticles exhibited spherical morphology and compatibility between HESP and excipients. NLCs achieved the highest wound closure percentage, supported by histological analysis and inflammatory biomarker outcomes. Cytotoxicity evaluation showed 87% cell viability compared to untreated HSF cells, and the skin irritancy test confirmed the safety of NLCs. <b>Conclusions:</b> TTO-loaded HESP-NLCs are promising candidates exhibiting superior wound-healing capabilities, making them a potential therapeutic option for cutaneous wound management.
Medicine, Pharmacy and materia medica
Eigenvalues and equivalence classes of third-order symmetric tensors
Lishan Fang, Hua-Lin Huang, Shengyuan Ruan
et al.
This paper demonstrates that third-order real symmetric tensors cannot be classified up to equivalence by their eigenvalues only, thereby resolving a problem posed by Qi in 2006. By applying Harrison's center theory, we derive equivalence classes of $2 \times 2 \times 2$ symmetric tensors via the one-to-one correspondence with the canonical forms of their associated binary cubics. For such tensors, we compute the explicit characteristic polynomials and discover two previously unknown coefficients using the combination resultant. Pairs of third-order real symmetric tensors of all dimensions with identical eigenvalues but belonging to different equivalence classes are constructed to illustrate the inapplicability of eigenvalues for classification.
Robust Planning and Control of Omnidirectional MRAVs for Aerial Communications in Wireless Networks
Giuseppe Silano, Daniel Bonilla Licea, Hajar El Hammouti
et al.
A new class of Multi-Rotor Aerial Vehicles (MRAVs), known as omnidirectional MRAVs (o-MRAVs), has gained attention for their ability to independently control 3D position and orientation. This capability enhances robust planning and control in aerial communication networks, enabling more adaptive trajectory planning and precise antenna alignment without additional mechanical components. These features are particularly valuable in uncertain environments, where disturbances such as wind and interference affect communication stability. This paper examines o-MRAVs in the context of robust aerial network planning, comparing them with the more common under-actuated MRAVs (u-MRAVs). Key applications, including physical layer security, optical communications, and network densification, are highlighted, demonstrating the potential of o-MRAVs to improve reliability and efficiency in dynamic communication scenarios.
Bridging Collaborative Filtering and Large Language Models with Dynamic Alignment, Multimodal Fusion and Evidence-grounded Explanations
Bo Ma, LuYao Liu, Simon Lau
et al.
Recent research has explored using Large Language Models for recommendation tasks by transforming user interaction histories and item metadata into text prompts, then having the LLM produce rankings or recommendations. A promising approach involves connecting collaborative filtering knowledge to LLM representations through compact adapter networks, which avoids expensive fine-tuning while preserving the strengths of both components. Yet several challenges persist in practice: collaborative filtering models often use static snapshots that miss rapidly changing user preferences; many real-world items contain rich visual and audio content beyond textual descriptions; and current systems struggle to provide trustworthy explanations backed by concrete evidence. Our work introduces \model{}, a framework that tackles these limitations through three key innovations. We develop an online adaptation mechanism that continuously incorporates new user interactions through lightweight modules, avoiding the need to retrain large models. We create a unified representation that seamlessly combines collaborative signals with visual and audio features, handling cases where some modalities may be unavailable. Finally, we design an explanation system that grounds recommendations in specific collaborative patterns and item attributes, producing natural language rationales users can verify. Our approach maintains the efficiency of frozen base models while adding minimal computational overhead, making it practical for real-world deployment.
Evaluation of micro-osteoperforations in expediting orthodontic tooth movement in adult patients
Mohammad K Alam, Balqees Alahmari
Background: Orthodontic tooth movement, the process of aligning teeth, can often be time-consuming, particularly in adult patients. Micro-osteoperforations (MOPs) have emerged as a potential technique to accelerate this process. Materials and Methods: A sample of 30 adult patients undergoing orthodontic treatment was selected. The patients were divided into two groups: an experimental group (EG) receiving MOPs and a control group (CG) without MOPs. Standard orthodontic treatment was administered to both groups. The rate of tooth movement was measured using digital models and recorded in millimeters per month. Pain levels reported by patients were also noted. The data were analyzed using basic statistical methods. Results: The EG demonstrated a significantly higher rate of orthodontic tooth movement compared to the CG. The average rate of tooth movement in the EG was 1.5 millimeters per month, while the CG exhibited an average rate of 0.8 millimeters per month. Additionally, pain levels reported by patients in the EG were slightly elevated immediately after MOPs but subsided within a few days. Conclusion: The findings of this study suggest that MOPs can effectively expedite orthodontic tooth movement in adult patients.
Pharmacy and materia medica, Analytical chemistry
Multi-modal Attribute Prompting for Vision-Language Models
Xin Liu, Jiamin Wu, and Wenfei Yang
et al.
Pre-trained Vision-Language Models (VLMs), like CLIP, exhibit strong generalization ability to downstream tasks but struggle in few-shot scenarios. Existing prompting techniques primarily focus on global text and image representations, yet overlooking multi-modal attribute characteristics. This limitation hinders the model's ability to perceive fine-grained visual details and restricts its generalization ability to a broader range of unseen classes. To address this issue, we propose a Multi-modal Attribute Prompting method (MAP) by jointly exploring textual attribute prompting, visual attribute prompting, and attribute-level alignment. The proposed MAP enjoys several merits. First, we introduce learnable visual attribute prompts enhanced by textual attribute semantics to adaptively capture visual attributes for images from unknown categories, boosting fine-grained visual perception capabilities for CLIP. Second, the proposed attribute-level alignment complements the global alignment to enhance the robustness of cross-modal alignment for open-vocabulary objects. To our knowledge, this is the first work to establish cross-modal attribute-level alignment for CLIP-based few-shot adaptation. Extensive experimental results on 11 datasets demonstrate that our method performs favorably against state-of-the-art approaches.
Study of the relationship between the severity of alcoholic cardiomyopathy and the level of alcohol consumption in male and female rats in the model of “home drinking”
S. A. Kryzhanovskii, I. B. Tsorin, E. O. Ionova
et al.
Background. Earlier, on the translational model of alcoholic cardiomyopathy (ACMP) developed by us in outbred white rats, which reproduces the main clinical diagnostic signs of this disease, it was shown that in rats of both sexes under conditions of constant 24/7 alcoholization for 24 weeks, AСMP is formed.This study purpose is a comparative assessment of the features of the ACM formation in male and female rats depending on the level of ethanol consumption in model experiments simulating "domestic drunkenness" with periodic alcoholization 24/2 for 24 weeks.Materials and methods. Experiments were performed on outbred white rats randomized into 4 groups: group 1 — control male rats (n=18), group 2 — control female rats (n = 18), group 3 — alcoholized male rats (n = 39) and group 4 — alcoholized female rats (n = 19). Control animals received a normal diet and free access to water. Animals of the 3rd and 4th groups weekly, for 24 weeks, from Friday 22.00 to Monday 8.00, received a 10 % ethanol solution as the only source of liquid with unlimited access to standard food, and the usual diet on the remaining days.Results. In animals of both sexes, after 24 weeks from the consumption start of the ethanol solution, ACM is formed, as evidenced by an increase in the end-systolic and end-diastolic sizes of the left ventricle of the heart (p = 0.0001) and a decrease in its ejection fraction (p = 0.0001), while the degree of pathological myocardial remodeling is more pronounced in females. According to cluster analysis, by the consumption of ethanol (CET), animals of both sexes are divided into 3 subgroups: low, medium and high CET, however, in males, the subgroup with an average CET prevails — 56 %, and in females with a high CET — 47 % (p = 0.0286), the low CET subgroup is minimal (16 %). At the same time, if in males in all subgroups, starting from the 8th week of alcoholization, CET dynamically decreases, then how in females in subgroups with medium and high CET, starting from the 16th week, it increases. It was found that the degree of left ventricular remodeling in females with high and moderate CET was almost 2 times higher than in males (p < 0.05).Conclusion. In model experiments imitating “domestic drunkenness”, it was shown that in females the intensity of the left ventricle heart remodeling is significantly higher than in males, which, apparently, is determined by the identified gender-dependent multidirectional trends in the formation of alcoholic behavior characterized by dynamic growth. consumption of ethanol in female rats as the duration of alcoholization increases.
Pharmacy and materia medica
Manganese Sulfate Nanocomposites Fabricated by Hot-Melt Extrusion for Chemodynamic Therapy of Colorectal Cancer
Da In Jeong, Sungyun Kim, Ja Seong Koo
et al.
The development of metal salts-based nanocomposites is highly desired for the Fenton or Fenton-like reaction-based chemodynamic therapy of cancer. Manganese sulfate (MnSO<sub>4</sub>)-dispersed nanoparticles (NPs) were fabricated with a hot-melt extrusion (HME) system for the chemodynamic therapy of colorectal cancer in this study. MnSO<sub>4</sub> was homogeneously distributed in polyethylene glycol (PEG) 6000 (as a hydrophilic polymer) with the aid of surfactants (Span 80 and Tween 80) by HME processing. Nano-size distribution was achieved after dispersing the pulverized extrudate of MnSO<sub>4</sub>-based composite in the aqueous media. The distribution of MnSO<sub>4</sub> in HME extrudate and the interactions between MnSO<sub>4</sub> and pharmaceutical additives were elucidated by Fourier-transform infrared, X-ray diffractometry, X-ray photoelectron spectroscopy, and scanning electron microscopy analyses. Hydroxyl radical generation efficiency by the Fenton-like chemistry capability of Mn<sup>2+</sup> ion was also confirmed by catalytic assays. By using the intrinsic H<sub>2</sub>O<sub>2</sub> in cancer cells, MnSO<sub>4</sub> NPs provided an elevated cellular reactive oxygen species level, apoptosis induction capability, and antiproliferation efficiency. The designed HME-processed MnSO<sub>4</sub> formulation can be efficiently used for the chemodynamic therapy of colorectal cancer.
Pharmacy and materia medica
Molecular Docking Study of Nigella sativa Alkaloid Compounds as the Inhibitor of Papain-Like Protease SARS-CoV-2
Gusnia Meilin Gholam, Iman Akhyar Firdausy
SARS-CoV-2 causes about 66% of China’s Wuhan market workers to experience fever, dry cough, and fatigue. Black cumin (Nigella sativa) is a plant with many benefits to cure many illnesses like hypertension, headache, infection, and inflammation. This study aimed to investigate the inhibition by compounds belonging to the Alkaloid group from Black Cumin Seed to inhibit PLpro activity as a target for SARS-CoV-2. The study used five alkaloid compounds ((2E,4E)-Decadienal, (2E,4Z)-Decadienal, Nigellicine, Nigellidine, and Nigellimine) from the Black cumin seed and a PLpro SARS-CoV-2 receptor (PDB ID: 6WX4). The methods used are ligand and receptor preparation, grid box validation, molecular docking, 2D and 3D visualisation, and data analysis using Gibbs free energy, type of interaction, and contact of amino acid residues data. This study used YASARA structure and BIOVIA Discovery Studio. The results showed that Nigellidine has the highest Gibbs free energy with a -2.67 kcal/mol score, higher than VIR251. PLpro has a catalytic triad at Cys111, His272, and Asp286 residues, the compound that binds to the active site is Nigellicine found at amino acid Cys111 with Pi-Sulfur.
Pharmacy and materia medica, Chemistry
Hemp (<i>Cannabis sativa</i> L., Kompolti cv.) and Hop (<i>Humulus lupulus</i> L., Chinook cv.) Essential Oil and Hydrolate: HS-GC-MS Chemical Investigation and Apoptotic Activity Evaluation
Elisa Ovidi, Valentina Laghezza Masci, Anna Rita Taddei
et al.
In this study, essential oils (EOs) and hydrolates (Hys) from Italian hemp (<i>Cannabis sativa</i> L. Kompolti cv.) and hop (<i>Humulus Lupulus</i> L., Chinook cv.) supply chains were chemically characterized and tested to investigate their apoptotic potential for the first time. Headspace–Gas Chromatography–Mass Spectrometry (HS-GC-MS) techniques were performed to describe their volatile chemical profile, highlighting a composition rich in terpene derivatives such as monoterpenes and sesquiterpenes among which <i>β</i>-myrcene, limonene, <i>β</i>-caryophyllene and <i>α</i>-humulene were the main constituents of EOs; in contrast, linalool, <i>cis</i>-<i>p</i>-menth-2,8-dien-1-ol, terpinen-4-ol, <i>α</i>-terpineol, caryophyllene oxide, and <i>τ</i>-cadinol were found in the Hys. The cytotoxicity activity on human leukemia cells (HL60), human neuroblastoma cells (SH-SY5Y), human metastatic adenocarcinoma breast cells (MCF7), human adenocarcinoma breast cells (MDA), and normal breast epithelial cell (MCF10A) for the EOs and Hys was studied by MTT assay and cytofluorimetric analysis and scanning and transmission electron microscopy were performed to define ultrastructural changes and the mechanism of cells death for HL 60 cells. An induction of the apoptotic mechanism was evidenced for hemp and hop EOs after treatment with the corresponding EC<sub>50</sub> dose. In addition, TEM and SEM investigations revealed typical characteristics induced by the apoptotic pathway. Therefore, thanks to the integration of the applied methodologies with the used techniques, this work provides an overview on the metabolomic profile and the apoptotic potential of hemp and hop EOs and, for the first time, also of Hys. The findings of this preliminary study confirm that the EOs and Hys from <i>Cannabis</i> and <i>Humulus</i> species are sources of bioactive molecules with multiple biological effects yet to be explored.
Medicine, Pharmacy and materia medica
DeLoRes: Decorrelating Latent Spaces for Low-Resource Audio Representation Learning
Sreyan Ghosh, Ashish Seth, and Deepak Mittal
et al.
Inspired by the recent progress in self-supervised learning for computer vision, in this paper we introduce DeLoRes, a new general-purpose audio representation learning approach. Our main objective is to make our network learn representations in a resource-constrained setting (both data and compute), that can generalize well across a diverse set of downstream tasks. Inspired from the Barlow Twins objective function, we propose to learn embeddings that are invariant to distortions of an input audio sample, while making sure that they contain non-redundant information about the sample. To achieve this, we measure the cross-correlation matrix between the outputs of two identical networks fed with distorted versions of an audio segment sampled from an audio file and make it as close to the identity matrix as possible. We use a combination of a small subset of the large-scale AudioSet dataset and FSD50K for self-supervised learning and are able to learn with less than half the parameters compared to state-of-the-art algorithms. For evaluation, we transfer these learned representations to 9 downstream classification tasks, including speech, music, and animal sounds, and show competitive results under different evaluation setups. In addition to being simple and intuitive, our pre-training algorithm is amenable to compute through its inherent nature of construction and does not require careful implementation details to avoid trivial or degenerate solutions. Furthermore, we conduct ablation studies on our results and make all our code and pre-trained models publicly available https://github.com/Speech-Lab-IITM/DeLoRes.
Polyelectrolytes Formulated with Primary Unconjugated Bile Acid Optimised Pharmacology of Bio-Engineered Implant
Armin Mooranian, Corina Mihaela Ionescu, Susbin Raj Wagle
et al.
Introduction. Several studies have shown that different biomaterials and hydrogels comprising various bile acids such as chenodeoxycholic acid (CDCA), as well as excipients such as poly-(styrene)-sulphonate (PSS) and poly-(allyl)-amine (PAA), exhibited positive biological effects on encapsulated viable pancreatic β-cells. Hence, this study aimed to investigate whether incorporating CDCA with PSS and PAA will optimise the functions of encapsulated pancreatic islets post-transplantation in Type 1 diabetes (T1D). Methods. Mice were made T1D, divided into two equal groups, and transplanted with encapsulated islets in PSS-PAA (control) or with CDCA-PSS-PAA (treatment) microcapsules. The effects of transplanted microcapsules on blood glucose, inflammation and the bile acid profile were measured post-transplantation. Results and Conclusion. Compared with control, the treatment group showed better survival rate, improved glycaemic control, and lower inflammatory profile, illustrated by ↓ interleukin 1-β, interleukin-6, interleukin-12, and tumour-necrosis factor-α, and ↓ levels of the bile acid, as well as lithocholic acid in the plasma, liver, large intestine and faeces. The results suggest that CDCA incorporation with PSS-PAA microcapsules exerted beneficial effects on encapsulated islets and resulted in enhanced diabetes treatment, post-transplantation, at the local and systemic levels.
Pharmacy and materia medica
Anomalous and Anisotropic Nonlinear Susceptibility in the Proximate Kitaev Magnet $α$-RuCl$_3$
Ludwig Holleis, Joseph Prestigiacomo, Zhijie Fan
et al.
The leading order nonlinear (NL) susceptibility, $χ_3$, in a paramagnet is negative and diverges as $T \rightarrow 0$. This divergence is destroyed when spins correlate and the NL response provides unique insights into magnetic order. Dimensionality, exchange interaction, and preponderance of quantum effects all imprint their signatures in the NL magnetic response. Here, we study the NL susceptibilities in the proximate Kitaev magnet $α$-RuCl$_3$ which differs from the expected antiferromagnetic behavior. For $T< T_c$ = 7.5 K and field $B$ in the ab-plane, we obtain contrasting NL responses in low ($<$ 2 ${T}$) and high field regions. For low fields the NL behavior is dominated by a quadratic response (positive $χ_2$), which shows a rapid rise below $T_c$. This large $χ_2 >0$ implies a broken sublattice symmetry of magnetic order at low temperatures. Classical Monte Carlo (CMC) simulations in the standard ${K-H-Γ}$ model secure such a quadratic ${B}$ dependence of ${M}$, only for ${T}$ $\approx$ ${T}_c$ with $χ_2$ being zero as ${T}$ $\rightarrow$ 0. It is also zero for all temperatures in exact diagonalization calculations. On the other hand, we find an exclusive cubic term ($χ_3$) describes the high field NL behavior well. $χ_3$ is large and positive both below and above ${T}_c$ crossing zero only for ${T}$ $>$ 50 K. In contrast, for $B$~$\parallel$~c-axis, no separate low/high field behaviors is measured and only a much smaller $χ_3$ is apparent.
A Novel Deep Learning Method for Thermal to Annotated Thermal-Optical Fused Images
Suranjan Goswami, Satish Kumar Singh, and Bidyut B. Chaudhuri
Thermal Images profile the passive radiation of objects and capture them in grayscale images. Such images have a very different distribution of data compared to optical colored images. We present here a work that produces a grayscale thermo-optical fused mask given a thermal input. This is a deep learning based pioneering work since to the best of our knowledge, there exists no other work on thermal-optical grayscale fusion. Our method is also unique in the sense that the deep learning method we are proposing here works on the Discrete Wavelet Transform (DWT) domain instead of the gray level domain. As a part of this work, we also present a new and unique database for obtaining the region of interest in thermal images based on an existing thermal visual paired database, containing the Region of Interest on 5 different classes of data. Finally, we are proposing a simple low cost overhead statistical measure for identifying the region of interest in the fused images, which we call as the Region of Fusion (RoF). Experiments on the database show encouraging results in identifying the region of interest in the fused images. We also show that they can be processed better in the mixed form rather than with only thermal images.