bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of pH-Responsive, Thermosensitive, Antibacterial, and Anticancer CS/PVA/Graphene Blended Hydrogels for Controlled Drug Delivery
Authors: Mansha Saira , Sajjad Amna , Zarbab Aneeqa , Afzal Tahmina , Kanwal Zakia , Iqbal Muhammad Javaid , Raza Mohsin Ali , Ali Sharafat
Published: March 2024

Drug delivery techniques based on polymers have been investigated for their potential to improve drug solubility, reduce systemic side effects, and controlled and targeted administration at infection site. In this study, we developed a co-polymeric hydrogel composed of graphene sheets (GNS), polyvinyl alcohol (PVA), and chitosan (CS) that is loaded with methotrexate (MTX) for in vitro liver cancer treatment. Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM) was employed to check the structural properties and surface morphology. Moreover, tests were conducted on the cytotoxicity, hemolytic activity, release kinetics, swelling behaviour and degradation of hydrogels. A controlled release of drug from hydrogel in PBS at pH 7.4 was examined using release kinetics. Maximal drug release in six hours was 97.34%. The prepared hydrogels did not encourage the HepG2 growth and were non-hemolytic. The current study highlights the potential of GNS-based hydrogel loaded with MTX as an encouraging therapy for hepatocellular carcinoma. HepG2 cell viability of MTX-loaded CS-PVA-GNS hydrogel was (IC50 5.87 µg/200 mL) in comparison to free MTX (IC50 5.03 µg/200 mL). These outcomes recommend that hydrogels with GNS ensure improved drug delivery in cancer microenvironment while lessening adverse consequences on healthy cells.
Can Digital Technologies Be Useful for Weight Loss in Individuals with Overweight or Obesity? A Systematic Review
Authors: Protano Carmela , De Giorgi Andrea , Valeriani Federica , Mazzeo Elisa , Zanni Stefano , Cofone Luigi , D’Ancona Gabriele , Hasnaoui Anis , Pindinello Ivano , Sabato Marise , Ubaldi Francesca , Volpini Veronica , Romano Spica Vincenzo , Vitali Matteo , Gallè Francesca
Published: March 2024

Digital technologies have greatly developed and impacted several aspects of life, including health and lifestyle. Activity tracking, mobile applications, and devices may also provide messages and goals to motivate adopting healthy behaviors, namely physical activity and dietary changes. This review aimed to assess the effectiveness of digital resources in supporting behavior changes, and thus influencing weight loss, in people with overweight or obesity. A systematic review was conducted according to the PRISMA guidelines. The protocol was registered in PROSPERO (CRD42023403364). Randomized Controlled Trials published from the database’s inception to 8 November 2023 and focused on digital-based technologies aimed at increasing physical activity for the purpose of weight loss, with or without changes in diet, were considered eligible. In total, 1762 studies were retrieved and 31 met the inclusion criteria. Although they differed in the type of technology used and in their design, two-thirds of the studies reported significantly greater weight loss among electronic device users than controls. Many of these studies reported tailored or specialist-guided interventions. The use of digital technologies may be useful to support weight-loss interventions for people with overweight or obesity. Personalized feedback can increase the effectiveness of new technologies in motivating behavior changes.
Temporal Responses of a Low-Energy Meal Replacement Plan or Exercise Training on Cardiovascular Function and Fibro-Inflammatory Markers in People with Type 2 Diabetes—A Secondary Analysis of the “Diabetes Interventional Assessment of Slimming or Training to Lessen Inconspicuous Cardiovascular Dysfunction” Study
Authors: Bilak Joanna M. , Gulsin Gaurav S. , Bountziouka Vasiliki , Parke Kelly S. , Redman Emma , Henson Joseph , Zhao Lei , Costet Phillipe , Cvijic Mary Ellen , Maya Juan , Chang Ching-Pin , Davies Melanie J. , Yates Thomas , McCann Gerry P. , Brady Emer M.
Published: March 2024

Background: This study assesses the temporal responses of cardiovascular function, fibro-inflammation, and glucometabolic profiles in asymptomatic adults with type 2 diabetes, following a low-energy meal replacement plan (MRP) or exercise training. Methods: Secondary analysis of DIASTOLIC: a randomised, open-label, blinded-endpoint trial of 12 weeks MRP (~810 kcal/day) or exercise training. Cardiac magnetic resonance, plasma fibroinflammatory, and metabolic markers were undertaken at baseline, 4, and 12 weeks. Results: Out of 24 participants in the MRP group and 22 in exercise training, 18 and 11 completed all three visits. MRP resulted in early (0–4 weeks) improvement in insulin resistance (HOMA-IR: 10.82 to 4.32), decrease in FABP-4 (4.87 ± 0.19 to 5.15 ± 0.32 mg/L), and improvement in left ventricular remodelling LV mass: volume (0.86 ± 0.14 to 0.78 ± 0.11), all with large effect sizes. MMP8 levels increased moderately at 4–12 weeks. Peak early diastolic strain rate (cPEDSR) initially decreased, then improved. Exercise training led to minor improvements in insulin resistance and MMP-8 levels, with no significant changes in cPEDSR or LV remodelling. Conclusions: MRP resulted in early improvements in insulin resistance, cardiac remodelling, and inflammation, but with an initial decrease in diastolic function, improving by 12 weeks. Exercise training showed minor early benefits in insulin resistance and inflammation, but no significant cardiac changes.
Review of Peripheral Blood Eosinophilia: Workup and Differential Diagnosis
Authors: Weaver Michael Dennis , Glass Bianca , Aplanalp Chance , Patel Gauri , Mazhil Jeshrine , Wang Isabella , Dalia Samir
Published: March 2024

Eosinophils are a type of granulocyte key to immune system modulation seen in a number of disease processes. Nearly every major organ system can be connected to peripheral eosinophilia through a number of different disease processes, ranging from benign conditions to malignancy. In this paper, we review both common and rare causes of peripheral eosinophilia, their symptoms, and a framework for the workup of peripheral eosinophilia of unknown etiology.
A Knowledge and Evaluation Model to Support the Conservation of Abandoned Historical Centres in Inner Areas
Authors: Trovato Maria Rosa , Sanzaro Deborah
Published: March 2024

The planning of interventions aimed at preserving the built heritage of inner areas is a complex process due to the fragility of these contexts. It should stem from adequate knowledge to support the recognition of qualities, resources, and potentials, and the reinterpretation of residual values. From the perspective of an axiological approach to the built heritage, it is possible to foster the resemantization of such values based on a rigorous cognitive model. This research proposed a cognitive model of the built heritage of the historic neighbourhood of Granfonte in Leonforte (Enna). The knowledge model, developed in Excel, has a hierarchical type of structure characterized by domain, classes, properties, and the attribution of values to properties. The approach makes it possible to execute queries that arise from specific relationships between classes. In this study, we developed both simple queries to measure the percentages of certain characteristics of the building units and complex queries for the estimation of aggregate indices to define the degree of transformation and loss of integrity ITI and degradation ID of the building units or to identify those most exposed to the risk of ruination and contagion. The proposed model can be framed within the framework of ontologies supporting structured heritage knowledge.
“Creative Anthropology” as a Unit for Knowing: Epistemic Object and Experimental System in Research-Creation “in” Clay
Authors: Potvin Yanik
Published: March 2024

This essay takes advantage of the current context of superdiversity to define a form of hybrid heuristics between North American anthropology and research-creation “in” the arts. In an attempt to alleviate the epistemological disaster described by Gregory Bateson as the loss of the unity of the biosphere and humanity, I position myself within a nomothetic perspective of Boasian anthropology and a postqualitative approach to research-creation. My research-creation proposes clay as an epistemic object and develops a creative methodology in the form of an experimental system that borrows from the following two types of change observable in living organisms: static and schismatic changes. The artistic activities, presented as two heuristic cycles, seek to broaden the self-reflexivity inherent in the use of clay by human groups. They provoke decentring leading to a loss of control where a new identity has to be defined. This reveals itself in terms of system thinking as the reconstruction of a new reality that is defined neither entirely by my artistic practice nor entirely by my theoretical framework derived from anthropology. It is a “place of passage” between both. It is a new identity that can be defined by the “change of change” that I call “creative anthropology”. This transdisciplinary approach introduces a “second glance” into anthropological research and opens up breaches through research-creation. It works to develop new narratives and test posthumanism in the field of my artistic practice.
Classical and Modern Prejudice toward Individuals with Intellectual Disabilities: The Role of Experienced Contact, Beliefs in a Just World and Social Dominance Orientation
Authors: Servidio Rocco , Cammarata Ivan Giuseppe , Scaffidi Abbate Costanza , Boca Stefano
Published: March 2024

This study investigates the impact of experienced contact on prejudiced attitudes towards individuals with intellectual disabilities (IDs), examining beliefs in a just world (BJW) and social dominance orientation (SDO) as potential serial mediators. Data were collected from 224 university students (M = 23.02, SD = 2.48). Path analysis modelling assessed the structural relationships between the study variables. The findings revealed that experienced contact was negatively and significantly associated with BJW and SDO. Additionally, BJW and SDO fully mediated the relationship between experienced contact and overt prejudice. These findings underscore the influence of individual differences on attitudes towards individuals with ID, establishing a crucial foundation for future research and the development of interventions aimed at reducing prejudice and discrimination.
What Are the Experiences of Mental Health Practitioners Involved in a Coroner’s Inquest and Other Inquiry Processes after an Unexpected Death of a Patient? A Systematic Review and Thematic Synthesis of the Literature
Authors: Tamworth Millie , Tekin Sahra , Billings Jo , Killaspy Helen
Published: March 2024

Grief after suicide or patient-perpetrated homicide can be complex for those involved in the patient’s care. Mental health practitioners with patients who die unexpectedly may be called to assist in the formal investigation processes that follow. The aim of this study was to examine the experience of mental health practitioners called to attend a coroner’s inquest or other forms of formal inquiry. A protocol for a systematic review was prospectively registered on PROSPERO (CRD42023400310). A thematic synthesis of existing literature was conducted. We identified six articles for inclusion and constructed three themes from our analysis: Blame and enduring hostility, In the dark, and Limited learning. We found mental health practitioners may construct narratives of self-blame. These can be reinforced by the investigatory processes that follow. Feedback from inquiries is often delivered haphazardly and may not reflect the realities of clinical work. The support given to assist practitioners through inquiry processes varied—both in amount and how helpful it was. The research conducted on this topic is limited. More qualitative research should be conducted to understand the factors that make this experience more or less difficult as well as well as what support is needed for whom.
A Review of Bayesian Spatiotemporal Models in Spatial Epidemiology
Authors: Wang Yufeng , Chen Xue , Xue Feng
Published: March 2024

Spatial epidemiology investigates the patterns and determinants of health outcomes over both space and time. Within this field, Bayesian spatiotemporal models have gained popularity due to their capacity to incorporate spatial and temporal dependencies, uncertainties, and intricate interactions. However, the complexity of modelling and computations associated with Bayesian spatiotemporal models vary across different diseases. Presently, there is a limited comprehensive overview of Bayesian spatiotemporal models and their applications in epidemiology. This article aims to address this gap through a thorough review. The review commences by delving into the historical development of Bayesian spatiotemporal models concerning disease mapping, prediction, and regression analysis. Subsequently, the article compares these models in terms of spatiotemporal data distribution, general spatiotemporal data models, environmental covariates, parameter estimation methods, and model fitting standards. Following this, essential preparatory processes are outlined, encompassing data acquisition, data preprocessing, and available statistical software. The article further categorizes and summarizes the application of Bayesian spatiotemporal models in spatial epidemiology. Lastly, a critical examination of the advantages and disadvantages of these models, along with considerations for their application, is provided. This comprehensive review aims to enhance comprehension of the dynamic spatiotemporal distribution and prediction of epidemics. By facilitating effective disease scrutiny, especially in the context of the global COVID-19 pandemic, the review holds significant academic merit and practical value. It also aims to contribute to the development of improved ecological and epidemiological prevention and control strategies.
Sequence Alignment-Based Prediction of Myosin 7A: Structural Implications and Protein Interactions
Authors: Yu Chan Jong , Park Yoon Ho , Ryu Bumhan , Jung Hyun Suk
Published: March 2024

Myosin, a superfamily of motor proteins, obtain the energy they require for movement from ATP hydrolysis to perform various functions by binding to actin filaments. Extensive studies have clarified the diverse functions performed by the different isoforms of myosin. However, the unavailability of resolved structures has made it difficult to understand the way in which their mechanochemical cycle and structural diversity give rise to distinct functional properties. With this study, we seek to further our understanding of the structural organization of the myosin 7A motor domain by modeling the tertiary structure of myosin 7A based on its primary sequence. Multiple sequence alignment and a comparison of the models of different myosin isoforms and myosin 7A not only enabled us to identify highly conserved nucleotide binding sites but also to predict actin binding sites. In addition, the actomyosin-7A complex was predicted from the protein–protein interaction model, from which the core interface sites of actin and the myosin 7A motor domain were defined. Finally, sequence alignment and the comparison of models were used to suggest the possibility of a pliant region existing between the converter domain and lever arm of myosin 7A. The results of this study provide insights into the structure of myosin 7A that could serve as a framework for higher resolution studies in future.
Resveratrol as a Promising Nutraceutical: Implications in Gut Microbiota Modulation, Inflammatory Disorders, and Colorectal Cancer
Authors: Prakash Vidhya , Bose Chinchu , Sunilkumar Damu , Cherian Robin Mathew , Thomas Shwetha Susan , Nair Bipin G.
Published: March 2024

Natural products have been a long-standing source for exploring health-beneficial components from time immemorial. Modern science has had a renewed interest in natural-products-based drug discovery. The quest for new potential secondary metabolites or exploring enhanced activities for existing molecules remains a pertinent topic for research. Resveratrol belongs to the stilbenoid polyphenols group that encompasses two phenol rings linked by ethylene bonds. Several plant species and foods, including grape skin and seeds, are the primary source of this compound. Resveratrol is known to possess potent anti-inflammatory, antiproliferative, and immunoregulatory properties. Among the notable bioactivities associated with resveratrol, its pivotal role in safeguarding the intestinal barrier is highlighted for its capacity to prevent intestinal inflammation and regulate the gut microbiome. A better understanding of how oxidative stress can be controlled using resveratrol and its capability to protect the intestinal barrier from a gut microbiome perspective can shed more light on associated physiological conditions. Additionally, resveratrol exhibits antitumor activity, proving its potential for cancer treatment and prevention. Moreover, cardioprotective, vasorelaxant, phytoestrogenic, and neuroprotective benefits have also been reported. The pharmaceutical industry continues to encounter difficulties administering resveratrol owing to its inadequate bioavailability and poor solubility, which must be addressed simultaneously. This report summarizes the currently available literature unveiling the pharmacological effects of resveratrol.
In Silico Analysis Highlights Potential Predictive Indicators Associated with Secondary Progressive Multiple Sclerosis
Authors: Calabrò Marco , Lui Maria , Mazzon Emanuela , D’Angiolini Simone
Published: March 2024

Multiple sclerosis (MS) is a complex inflammatory disease affecting the central nervous system. Most commonly, it begins with recurrent symptoms followed by partial or complete recovery, known as relapsing–remitting MS (RRMS). Over time, many RRMS patients progress to secondary progressive MS (SPMS), marked by gradual symptom deterioration. The factors triggering this transition remain unknown, lacking predictive biomarkers. This study aims to identify blood biomarkers specific to SPMS. We analyzed six datasets of SPMS and RRMS patients’ blood and brain tissues, and compared the differential expressed genes (DEGs) obtained to highlight DEGs reflecting alterations occurring in both brain and blood tissues and the potential biological processes involved. We observed a total of 38 DEGs up-regulated in both blood and brain tissues, and their interaction network was evaluated through network analysis. Among the aforementioned DEGs, 21 may be directly involved with SPMS transition. Further, we highlighted three biological processes, including the calcineurin–NFAT pathway, related to this transition. The investigated DEGs may serve as a promising means to monitor the transition from RRMS to SPMS, which is still elusive. Given that they can also be sourced from blood samples, this approach could offer a relatively rapid and convenient method for monitoring MS and facilitating expedited assessments.
State-of-the-Art Differentiation Protocols for Patient-Derived Cardiac Pacemaker Cells
Authors: Torre Eleonora , Mangoni Matteo E. , Lacampagne Alain , Meli Albano C. , Mesirca Pietro
Published: March 2024

Human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes raise the possibility of generating pluripotent stem cells from a wide range of human diseases. In the cardiology field, hiPSCs have been used to address the mechanistic bases of primary arrhythmias and in investigations of drug safety. These studies have been focused primarily on atrial and ventricular pathologies. Consequently, many hiPSC-based cardiac differentiation protocols have been developed to differentiate between atrial- or ventricular-like cardiomyocytes. Few protocols have successfully proposed ways to obtain hiPSC-derived cardiac pacemaker cells, despite the very limited availability of human tissues from the sinoatrial node. Providing an in vitro source of pacemaker-like cells would be of paramount importance in terms of furthering our understanding of the mechanisms underlying sinoatrial node pathophysiology and testing innovative clinical strategies against sinoatrial node dysfunction (i.e., biological pacemakers and genetic- and pharmacological- based therapy). Here, we summarize and detail the currently available protocols used to obtain patient-derived pacemaker-like cells.
Molecular Pharmacology of Gelsemium Alkaloids on Inhibitory Receptors
Authors: Marileo Ana M. , Lara César O. , Sazo Anggelo , Contreras Omayra V. , González Gabriel , Castro Patricio A. , Aguayo Luis G. , Moraga-Cid Gustavo , Fuentealba Jorge , Burgos Carlos F. , Yévenes Gonzalo E.
Published: March 2024

Indole alkaloids are the main bioactive molecules of the Gelsemium genus plants. Diverse reports have shown the beneficial actions of Gelsemium alkaloids on the pathological states of the central nervous system (CNS). Nevertheless, Gelsemium alkaloids are toxic for mammals. To date, the molecular targets underlying the biological actions of Gelsemium alkaloids at the CNS remain poorly defined. Functional studies have determined that gelsemine is a modulator of glycine receptors (GlyRs) and GABAA receptors (GABAARs), which are ligand-gated ion channels of the CNS. The molecular and physicochemical determinants involved in the interactions between Gelsemium alkaloids and these channels are still undefined. We used electrophysiological recordings and bioinformatic approaches to determine the pharmacological profile and the molecular interactions between koumine, gelsemine, gelsevirine, and humantenmine and these ion channels. GlyRs composed of α1 subunits were inhibited by koumine and gelsevirine (IC50 of 31.5 ± 1.7 and 40.6 ± 8.2 μM, respectively), while humantenmine did not display any detectable activity. The examination of GlyRs composed of α2 and α3 subunits showed similar results. Likewise, GABAARs were inhibited by koumine and were insensitive to humantenmine. Further assays with chimeric and mutated GlyRs showed that the extracellular domain and residues within the orthosteric site were critical for the alkaloid effects, while the pharmacophore modeling revealed the physicochemical features of the alkaloids for the functional modulation. Our study provides novel information about the molecular determinants and functional actions of four major Gelsemium indole alkaloids on inhibitory receptors, expanding our knowledge regarding the interaction of these types of compounds with protein targets of the CNS.
Polydopamine-Coated Liposomes for Methylene Blue Delivery in Anticancer Photodynamic Therapy: Effects in 2D and 3D Cellular Models
Authors: De Leo Vincenzo , Marras Emanuela , Maurelli Anna Maria , Catucci Lucia , Milano Francesco , Gariboldi Marzia Bruna
Published: March 2024

Photodynamic therapy (PDT) is a therapeutic option for cancer, in which photosensitizer (PS) drugs, light, and molecular oxygen generate reactive oxygen species (ROS) and induce cell death. First- and second-generation PSs presented with problems that hindered their efficacy, including low solubility. Thus, second-generation PSs loaded into nanocarriers were produced to enhance their cellular uptake and therapeutic efficacy. Among other compounds investigated, the dye methylene blue (MB) showed potential as a PS, and its photodynamic activity in tumor cells was reported even in its nanocarrier-delivered form, including liposomes. Here, we prepared polydopamine (PDA)-coated liposomes and efficiently adsorbed MB onto their surface. lipoPDA@MB vesicles were first physico-chemically characterized and studies on their light stability and on the in vitro release of MB were performed. Photodynamic effects were then assessed on a panel of 2D- and 3D-cultured cancer cell lines, comparing the results with those obtained using free MB. lipoPDA@MB uptake, type of cell death induced, and ability to generate ROS were also investigated. Our results show that lipoPDA@MB possesses higher photodynamic potency compared to MB in both 2D and 3D cell models, probably thanks to its higher uptake, ROS production, and apoptotic cell death induction. Therefore, lipoPDA@MB appears as an efficient drug delivery system for MB-based PDT.
The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain
Authors: Martos Diána , Lőrinczi Bálint , Szatmári István , Vécsei László , Tanaka Masaru
Published: March 2024

The central nervous system (CNS) is the final frontier in drug delivery because of the blood–brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions, and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain-modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically, SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open-field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 μmol/4 μL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 μmol/4 μL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.
In Vivo Detection of Metabolic Fluctuations in Real Time Using the NanoBiT Technology Based on PII Signalling Protein Interactions
Authors: Rozbeh Rokhsareh , Forchhammer Karl
Published: March 2024

New protein-fragment complementation assays (PCA) have successfully been developed to characterize protein–protein interactions in vitro and in vivo. Notably, the NanoBiT technology, employing fragment complementation of NanoLuc luciferase, stands out for its high sensitivity, wide dynamic range, and straightforward read out. Previously, we explored the in vitro protein interaction dynamics of the PII signalling protein using NanoBiT, revealing significant modulation of luminescence signals generated by the interaction between PII and its receptor protein NAGK by 2-oxoglutarate levels. In the current work, we investigated this technology in vivo, to find out whether recombinantly expressed NanoBiT constructs using the NanoLuc large fragment fused to PII and PII-interaction partners NAGK or PipX-fused to the NanoLuc Small BiT are capable of detecting the metabolic fluctuations in Escherichia coli. Therefore, we devised an assay capable of capturing the metabolic responses of E. coli cells, demonstrating real-time metabolic perturbation upon nitrogen upshift or depletion treatments. In particular, the PII-NAGK NanoBitT sensor pair reported these changes in a highly sensitive manner.
Ionization Cross Sections of Hydrogen Molecule by Electron and Positron Impact
Authors: Tőkési Károly , DuBois Robert D.
Published: March 2024

We present ionization cross sections of hydrogen molecules by electron and positron impact for impact energies between 20 and 1000 eV. A three-body Classical Trajectory Monte Carlo approximation is applied to mimic the collision system. In this approach, the H2 molecule is modeled by a hydrogen-type atom with one active electron bound to a central core of effective charge with an effective binding energy. Although this model is crude for describing a hydrogen molecule, we found that the total cross sections for positron impact agree reasonably well with the experimental data. For the electron impact, our calculated cross sections are in good agreement with the experimental data in impact energies between 80 eV and 400 eV but are smaller at higher impact energies and larger at lower impact energies. Our calculated cross sections are compared with the scaled cross sections obtained experimentally for an atomic hydrogen target. We also present single differential cross sections as a function of the energy and angle of the ejected electron and scattered projectiles for a 250 eV impact. These are shown to agree well with available data. Impact parameter distributions are also compared for several impact energies.
Transcutaneous Auricular Vagus Nerve Stimulation Alleviates Monobenzone-Induced Vitiligo in Mice
Authors: Luo Shiqi , Meng Xinghua , Ai Jing , Zhang Zhihong , Dai Yanfeng , Yu Xiang
Published: March 2024

Vitiligo is a complex skin disorder that involves oxidative stress and inflammatory responses and currently lacks a definitive cure. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive method for targeting the auricular branch of the vagus nerve and has gained widespread attention for potential intervention in the autonomic nervous system. Although previous research has suggested that vagus nerve stimulation can potentially inhibit inflammatory responses, its specific role and mechanisms in vitiligo treatment remain unknown. This study aimed to explore the therapeutic effects of taVNS in a mouse model of vitiligo induced by monobenzone. Initially, a quantitative assessment of the treatment effects on vitiligo mice was conducted using a scoring system, revealing that taVNS significantly alleviated symptoms, particularly by reducing the depigmented areas. Subsequent immunohistochemical analysis revealed the impact of taVNS treatment on melanocyte granules, mitigating pigment loss in the skin of monobenzone-induced vitiligo mice. Further analysis indicated that taVNS exerted its therapeutic effects through multiple mechanisms, including the regulation of oxidative stress, enhancement of antioxidant capacity, promotion of tyrosine synthesis, and suppression of inflammatory responses. The conclusions of this study not only emphasize the potential value of taVNS in vitiligo therapy, but also lay a foundation for future research into the mechanisms and clinical applications of taVNS.
New Strategies for Macrophage Re-Education in Cancer: An Update
Authors: Lampiasi Nadia
Published: March 2024

The association between cancer and inflammation is well established. Chronic inflammation represents a fundamental step in the development and progression of some types of cancer. Tumors are composed of a heterogeneous population of infiltrating cells including macrophages, fibroblasts, lymphocytes, granulocytes, and mast cells, which respond to signals from the microenvironment and, in turn, produce cytokines, chemokines, transcription factors, receptors, and miRNAs. Recent data demonstrate that, in addition to classical (M1) and alternative (M2) macrophage subtypes, there are many intermediate subtypes that potentially play different roles in response to environmental stimuli. Tumors are infiltrated by macrophages called TAMs that mainly display an M2-like phenotype and tumor growth-permissive activities. There is a bidirectional interaction between tumor cells and tumor-infiltrating cells that determines macrophage polarization and ultimately tumor progression or regression. These complex interactions are still unclear but understanding them is fundamental for the development of new therapeutic strategies. Re-educating tumor-permissive macrophages into anti-tumor macrophages is a new focus of research. This review aims to analyze the most recent articles investigating the interplay between tumors, tumor-infiltrating cells, and TAMs, and the strategies for re-educating tumor-permissive macrophages.
Standard Doses of Cholecalciferol Reduce Glucose and Increase Glutamine in Obesity-Related Hypertension: Results of a Randomized Trial
Authors: Santos Catarina , Carvalho Rui , Fonseca Ana Mafalda , Castelo Branco Miguel , Alves Marco , Jarak Ivana
Published: March 2024

In arterial hypertension, the dysregulation of several metabolic pathways is closely associated with chronic immune imbalance and inflammation progression. With time, these disturbances lead to the development of progressive disease and end-organ involvement. However, the influence of cholecalciferol on metabolic pathways as a possible mechanism of its immunomodulatory activity in obesity-related hypertension is not known. In a phase 2, randomized, single-center, 24-week trial, we evaluated, as a secondary outcome, the serum metabolome of 36 age- and gender-matched adults with obesity-related hypertension and vitamin D deficiency, before and after supplementation with cholecalciferol therapy along with routine medication. The defined endpoint was the assessment of circulating metabolites using a nuclear magnetic resonance-based metabolomics approach. Univariate and multivariate analyses were used to evaluate the systemic metabolic alterations caused by cholecalciferol. In comparison with normotensive controls, hypertensive patients presented overall decreased expression of several amino acids (p < 0.05), including amino acids with ketogenic and glucogenic properties as well as aromatic amino acids. Following cholecalciferol supplementation, increases were observed in glutamine (p < 0.001) and histidine levels (p < 0.05), with several other amino acids remaining unaffected. Glucose (p < 0.05) and acetate (p < 0.05) decreased after 24 weeks in the group taking the supplement, and changes in the saturation of fatty acids (p < 0.05) were also observed, suggesting a role of liposoluble vitamin D in lipid metabolism. Long-term cholecalciferol supplementation in chronically obese and overweight hypertensives induced changes in the blood serum metabolome, which reflected systemic metabolism and may have fostered a new microenvironment for cell proliferation and biology. Of note, the increased availability of glutamine may be relevant for the proliferation of different T-cell subsets.
Aspirin Caused Intestinal Damage through FXR and ET-1 Signaling Pathways
Authors: Lin Qiuxia , Zhang Binbin , Dai Manyun , Cheng Yan , Li Fei
Published: March 2024

Aspirin is a non-steroidal, anti-inflammatory drug often used long term. However, long-term or large doses will cause gastrointestinal adverse reactions. To explore the mechanism of intestinal damage, we used non-targeted metabolomics; farnesoid X receptor (FXR) knockout mice, which were compared with wild-type mice; FXR agonists obeticholic acid (OCA) and chenodeoxycholic acid (CDCA); and endothelin-producing inhibitor estradiol to explore the mechanisms of acute and chronic intestinal injuries induced by aspirin from the perspective of molecular biology. Changes were found in the bile acids taurocholate acid (TCA) and tauro-β-muricholic acid (T-β-MCA) in the duodenum, and we detected a significant inhibition of FXR target genes. After additional administration of the FXR agonists OCA and CDCA, duodenal villus damage and inflammation were effectively improved. The results in the FXR knockout mice and wild-type mice showed that the overexpression of endothelin 1 (ET-1) was independent of FXR regulation after aspirin exposure, whereas CDCA was able to restore the activation of ET-1, which was induced by aspirin in wild-type mice in an FXR-dependent manner. The inhibition of ET-1 production could also effectively protect against small bowel damage. Therefore, the study revealed the key roles of the FXR and ET-1 pathways in acute and chronic aspirin-induced intestinal injuries, as well as strategies on alleviating aspirin-induced gastrointestinal injury by activating FXR and inhibiting ET-1 overexpression.
Domestication Gene Mlx and Its Partner Mondo Are Involved in Controlling the Larval Body Size and Cocoon Shell Weight of Bombyx mori
Authors: Qin Xiaoxuan , Jiang Liang , Zhao Ping , Lin Ying , Zhang Yi , Xia Qingyou
Published: March 2024

Bombyx mori was domesticated from Bombyx mandarina. The long-term domestication of the silkworm has brought about many remarkable changes to its body size and cocoon shell weight. However, the molecular mechanism underlying the improvement in the economic characteristics of this species during domestication remains unclear. In this study, we found that a transposable element (TE)—Bm1—was present in the upstream regulatory region of the Mlx (Max-like protein X) gene in wild silkworms but not in all domesticated silkworms. The absence of Bm1 caused an increase in the promoter activity and mRNA content of Mlx. Mlx and its partner Mondo belong to the bHLHZ transcription factors family and regulate nutrient metabolism. RNAi of Mlx and Mondo decreased the expression and promoter activity of glucose metabolism-related genes (trehalose transport (Tret), phosphofructokinase (PFK), and pyruvate kinase (PK)), lipogenic genes (Acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS)), and glutamine synthesis gene (Glutamine synthase 2, (GS2)). Furthermore, the transgenic overexpression of Mlx and Mondo in the fat body of silkworms increased the larval body size, cocoon shell weight, and egg number, but the silencing of the two genes resulted in the opposite phenotypes. Our results reveal the molecular mechanism of Mlx selection during domestication and its successful use in the molecular breeding of Bombyx mori.
Tumor-Targeted Squaraine Dye for Near-Infrared Fluorescence-Guided Photodynamic Therapy
Authors: Park Yoonbin , Park Min Ho , Hyun Hoon
Published: March 2024

Many efforts have been made to develop near-infrared (NIR) fluorescent dyes with high efficiency for the NIR laser-induced phototherapy of cancer. However, the low tumor targetability and high nonspecific tissue uptake of NIR dyes in vivo limit their applications in preclinical cancer imaging and therapy. Among the various NIR dyes, squaraine (SQ) dyes are widely used due to their high molar extinction coefficient, intense fluorescence, and excellent photostability. Previously, benzoindole-derived SQ (BSQ) was prepared by incorporating carboxypentyl benzoindolium end groups into a classical SQ backbone, followed by conjugating with cyclic RGD peptides for tumor-targeted imaging. In this study, we demonstrate that the structure-inherent tumor-targeting BSQ not only shows a high fluorescence quantum yield in serum but also exhibits superior reactive oxygen species (ROS) generation capability under the 671 nm laser irradiation for effective photodynamic therapy (PDT) in vitro and in vivo. Without targeting ligands, the BSQ was preferentially accumulated in tumor tissue 24 h post-injection, which was the optimal timing of the laser irradiation to induce increments of ROS production. Therefore, this work provides a promising strategy for the development of photodynamic therapeutic SQ dyes for targeted cancer therapy.
On the Development of Inkjet-Printed Band Pass Filters Based on the Microstrip Hairpin Structure
Authors: Gugliandolo Giovanni , Quattrocchi Antonino , Campobello Giuseppe , Crupi Giovanni , Donato Nicola
Published: March 2024

In recent years, inkjet printing has emerged as a promising advanced fabrication technology in the field of electronics, offering remarkable advantages in terms of cost-effectiveness, design flexibility, and rapid prototyping. For these reasons, inkjet printing technology has been widely adopted in various applications, including printed circuit board fabrication, sensor development (e.g., temperature, humidity, and pressure sensing), and antenna and filter production, up to the microwave frequency range. The present paper is focused on the investigation of a methodology based on Monte Carlo simulations for quantitatively assessing the influence of fabrication tolerances on the performance of inkjet-printed microwave devices. In particular, the proposed methodology is applied to an inkjet-printed hairpin band pass filter specifically tailored for operation in the L band (i.e., from 1 GHz to 2 GHz). The initial design phase involved the use of computer aided design (CAD) software to optimize the geometric dimensions of the designed filter to closely match the desired performance specifications in terms of bandwidth, insertion loss, and return loss. Later, a Monte Carlo analysis was conducted to evaluate the propagation of tolerances in the fabrication process throughout the design and to estimate their effects on device performance. The fabrication process exploited the advanced capabilities of the Voltera inkjet printer, which was used to deposit a silver-based conductive ink on a commercial Rogers substrate. The device’s performance was evaluated by comparing the simulated scattering parameters with those measured on the developed filter using a vector network analyzer (VNA), thus ensuring accurate validation of real-world performance.
A Portable Tool for Spectral Analysis of Plant Leaves That Incorporates a Multichannel Detector to Enable Faster Data Capture
Authors: Botero-Valencia Juan , Reyes-Vera Erick , Ospina-Rojas Elizabeth , Prieto-Ortiz Flavio
Published: March 2024

In this study, a novel system was designed to enhance the efficiency of data acquisition in a portable and compact instrument dedicated to the spectral analysis of various surfaces, including plant leaves, and materials requiring characterization within the 410 to 915 nm range. The proposed system incorporates two nine-band detectors positioned on the top and bottom of the target surface, each equipped with a digitally controllable LED. The detectors are capable of measuring both reflection and transmission properties, depending on the LED configuration. Specifically, when the upper LED is activated, the lower detector operates without its LED, enabling the precise measurement of light transmitted through the sample. The process is reversed in subsequent iterations, facilitating an accurate assessment of reflection and transmission for each side of the target surface. For reliability, the error estimation utilizes a color checker, followed by a multi-layer perceptron (MLP) implementation integrated into the microcontroller unit (MCU) using TinyML technology for real-time refined data acquisition. The system is constructed with 3D-printed components and cost-effective electronics. It also supports USB or Bluetooth communication for data transmission. This innovative detector marks a significant advancement in spectral analysis, particularly for plant research, offering the potential for disease detection and nutritional deficiency assessment.
The Scope and Impact of Viral Infections in Common Variable Immunodeficiency (CVID) and CVID-like Disorders: A Literature Review
Authors: Al-Hakim Adam , Kacar Mark , Savic Sinisa
Published: March 2024

Common Variable Immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disorder characterised by impaired antibody production, leading to recurrent infections and an increased susceptibility to viral pathogens. This literature review aims to provide a comprehensive overview of CVID’s relationship with viral infections, encompassing disease pathogenesis, key presenting features, specific monogenic susceptibilities, the impact of COVID-19, and existing treatment options. The pathogenesis of CVID involves complex immunological dysregulation, including defects in B cell development, antibody class switching, and plasma cell differentiation. These abnormalities contribute to an impaired humoral immune response against viral agents, predisposing individuals with CVID to a broad range of viral infections. Genetic factors play a prominent role in CVID, and monogenic drivers of CVID-like disease are increasingly identified through advanced genomic studies. Some monogenic causes of the CVID-like phenotype appear to cause specific viral susceptibilities, and these are explored in the review. The emergence of the COVID-19 pandemic highlighted CVID patients’ heightened predisposition to severe outcomes with viral infections. This review explores the clinical manifestations, outcomes, and potential therapeutic approaches for COVID-19 in CVID patients. It assesses the efficacy of prophylactic measures for COVID-19, including vaccination and immunoglobulin replacement therapy, as well as trialled therapies.
De Novo Metabolic Syndrome 1 Year after Liver Transplantation and Its Association with Mid- and Long-Term Morbidity and Mortality in Liver Recipients
Authors: Czarnecka Kinga , Czarnecka Paulina , Tronina Olga , Bączkowska Teresa , Durlik Magdalena
Published: March 2024

Background: Metabolic syndrome (MS) constitutes an important source of cardiovascular- and cancer-related morbidity and mortality in the general population. Limited information is available on whether these findings can be directly extrapolated to liver recipients. This study aimed to investigate the impact of post-transplant MS present 1 year after liver transplantation on survival rates, risk of major cardiovascular events (CVEs), and de novo malignancies. Methods: Adult deceased-liver-donor recipients who underwent transplantation in our centre between 2010 and 2019 and reached at least 1 year of post-transplantation follow-up were eligible. Results: Of 259 enrolled patients, 20% developed post-transplant MS 1 year after the procedure. The presence of post-transplant MS at 1 year did not affect all-cause mortality (p = 0.144) and risk of de novo malignancies (p = 0.198) in liver recipients. However, it was associated with an overall and time-dependent increase in the risk of major CVEs (p < 0.001). MASH aetiology of liver disease, pre-existing major CVEs, and development of de novo malignancy were independent predictors of all-cause mortality in liver recipients. Conclusions: New onset MS exerts a wide-ranging effect on the post-transplant prognosis of liver recipients. Obtaining optimal control over all modifiable metabolic risk factors is central to improving long-term outcomes in this population.
Research on the Deployment of Professional Rescue Ships for Maritime Traffic Safety under Limited Conditions
Authors: Shao Minghui , Wu Biao , Li Yan , Jiang Xiaoli
Published: March 2024

This paper focuses on optimizing the deployment plan for standby points of professional rescue vessels based on the data of maritime incidents in the Beihai area of China. The primary objective is to achieve multi-level and multiple coverage of the jurisdictional waters of the Beihai Rescue Bureau. Models including the coverage quality of the jurisdictional waters, the coverage quality in high-risk areas, the maximum coverage of jurisdictional areas, and the maximum coverage of high-risk areas are constructed and solved using 0–1 integer programming. The optimal plan for eight standby points and their corresponding deployment plans for rescue vessels are obtained. A comparison with the current site selection plan of the Beihai Rescue Bureau validates the superiority of the proposed deployment plan for rescue vessel standby points in this paper.