bluuebunny/crossref_metadata_2025 huggingface dataset:
Particle Detection in Free-Falling Nanoliter Droplets
Authors: Sturm Fabian , Zieger Viktoria , Koltay Peter , Frejek Daniel , Kartmann Sabrina
Published: June 2024

Sorting and dispensing distinct numbers of cellular aggregates enables the creation of three-dimensional (3D) in vitro models that replicate in vivo tissues, such as tumor tissue, with realistic metabolic properties. One method for creating these models involves utilizing Drop-on-Demand (DoD) dispensing of individual Multicellular Spheroids (MCSs) according to material jetting processes. In the DoD approach, a droplet dispenser ejects droplets containing these MCSs. For the reliable printing of tissue models, the exact number of dispensed MCSs must be determined. Current systems are designed to detect MCSs in the nozzle region prior to the dispensing process. However, due to surface effects, in some cases the spheroids that are detected adhere to the nozzle and are not dispensed with the droplet as expected. In contrast, detection that is carried out only after the droplet has been ejected is not affected by this issue. This work presents a system that can detect micrometer-sized synthetic or biological particles within free-falling droplets with a volume of about 30 nanoliters. Different illumination modalities and detection algorithms were tested. For a glare point projection-based approach, detection accuracies of an average of 95% were achieved for polymer particles and MCF-7 spheroids with diameters above 75 μm. For smaller particles the detection accuracy was still in the range of 70%. An approach with diffuse white light illumination demonstrated an improvement for the detection of small opaque particles. Accuracies up to 96% were achieved using this concept. This makes the two demonstrated methods suitable for improving the accuracy and quality control of particle detection in droplets for Drop-on-Demand techniques and for bioprinting.
Miniaturized Active-Frequency Selective Surfaces for Low-Power Internet of Things Devices
Authors: Zhang Liang , Yang Haobin , Wang Yan , Zhang Shaoqing , Ding Tongyu
Published: June 2024

With the proliferation of smart devices, the Internet of Things (IoT) is rapidly expanding. This study proposes a miniaturized controllable metamaterial with low control voltage for achieving low-power and compact designs in IoT node devices. Operating at a target frequency of 2.4 GHz, the proposed metamaterial requires only a 3.3 V control voltage and occupies approximately one-third of the wavelength in size. Experimental validation demonstrates its excellent reflective control performance, positioning it as an ideal choice for low-power IoT systems, particularly in the context of miniaturized and low-power IoT node applications.
RGO/CuCl-Based Flexible Gas Sensor for High-Concentration Carbon Monoxide Gas Detection at Room Temperature
Authors: Liu Qingqing , Zhang Fuzheng , Pei Mengfei , Jiang Weile
Published: June 2024

Carbon monoxide (CO) gas sensors are widely used, especially for environmental monitoring in confined spaces such as the landscape of mining cave ruins in mining parks, which is essential for ensuring the health and safety of tourists and staff. In this paper, a flexible CO gas sensor based on polyimide, interdigital electrodes, and reduced graphene oxide (RGO)/cuprous chloride (CuCl) composite film is designed and manufactured for reliable room temperature detection of high-concentration CO gas. The structure size of RGO/CuCl gas-sensitive film is 5 × 5 mm. The RGO with a 62.65% C-C bond is prepared by the thermal reduction method. The test results show that the sensor has a high response in the range of 400–2000 ppm CO gas concentration, and the maximum response is 1.56. The linear correlation coefficient of the sensor is 0.981, which indicates that the sensor has good output response characteristics. The response time of the sensor for 400 ppm CO gas is 332 s, which indicates that the sensor has a fast response rate. Furthermore, compared with other gases, the sensor shows higher gas selectivity for CO gas. This sensor has the characteristics of small size and easy attachment; therefore, it can be installed on the shoulder or helmet of tourists’ safety suits, providing personalized real-time warning prompts for tourists’ physical health status.
GRU-ESO Strategy for a Distributed Coil Magnetically Levitated Planar Micromotor
Authors: Du Chaofan , Ming Zhengfeng , Ming Yue , Liu Ding , Li Yongzheng , Zhao Yuhu
Published: June 2024

Traditional magnetic levitation planar micromotors suffer from poor controllability, short travel range, low interference resistance, and low precision. To address these issues, a distributed coil magnetically levitated planar micromotor with a gated recurrent unit (GRU)-extended state observer (ESO) control strategy is proposed in this paper. First, the structural design of the distributed coil magnetically levitated planar micromotor employs a separation of levitation and displacement, reducing system coupling and increasing controllability and displacement range. Then, theoretical analysis and model establishment of the system are conducted based on the designed distributed coil magnetically levitated planar micromotor and its working principles, followed by simulation verification. Finally, based on the established system model, a GRU-ESO controller is designed. An ESO feedback control term is introduced to enhance the system’s anti-interference capability, and the GRU feedforward compensation control term is used to improve the system’s tracking control accuracy. The experimental results demonstrate the reliability of the designed distributed coil magnetic levitation planar micromotor and the effectiveness of the controller.
Design and Fabrication of Biosensor for a Specific Microbe by Silicon-Based Interference Color System
Authors: Sivakumar Muthusamy , Ervanan Sangami , Lakshmanan Susithra , Venkatesan Sathya , Kinoshita Takatoshi , Lakshmi Duraikkannu Shanthana , Kumar Alagarsamy Santhana Krishna
Published: June 2024

In this paper, one of the great challenges faced by silicon-based biosensors is resolved using a biomaterial multilayer. Tiny biomolecules are deposited on silicon substrates, producing devices that have the ability to act as iridescent color sensors. The color is formed by a coating of uniform microstructures through the interference of light. The system exploits a flat, RNA-aptamer-coated silicon-based surface to which captured microbes are covalently attached. Silicon surfaces are encompassed with the layer-by-layer deposition of biomolecules, as characterized by atomic force microscopy and X-ray photoelectron spectroscopy. Furthermore, the results demonstrate an application of an RNA aptamer chip for sensing a specific bacterium. Interestingly, the detection limit for the microbe was observed to be 2 × 106 CFUmL−1 by visually observed color changes, which were confirmed further using UV-Vis reflectance spectrophotometry. In this report, a flexible method has been developed for the detection of the pathogen Sphingobium yanoikuyae, which is found in non-beverage alcohols. The optimized system is capable of detecting the specific target microbe. The simple concept of these iridescent color changes is mainly derived from the increase in thickness of the nano-ordered layers.
Zeolite and Neurodegenerative Diseases
Authors: Panaiotov Stefan , Tancheva Lyubka , Kalfin Reni , Petkova-Kirova Polina
Published: June 2024

Neurodegenerative diseases (NDs), characterized by progressive degeneration and death of neurons, are strongly related to aging, and the number of people with NDs will continue to rise. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs, and the current treatments offer no cure. A growing body of research shows that AD and especially PD are intricately related to intestinal health and the gut microbiome and that both diseases can spread retrogradely from the gut to the brain. Zeolites are a large family of minerals built by [SiO4]4− and [AlO4]5− tetrahedrons joined by shared oxygen atoms and forming a three-dimensional microporous structure holding water molecules and ions. The most widespread and used zeolite is clinoptilolite, and additionally, mechanically activated clinoptilolites offer further improved beneficial effects. The current review describes and discusses the numerous positive effects of clinoptilolite and its forms on gut health and the gut microbiome, as well as their detoxifying, antioxidative, immunostimulatory, and anti-inflammatory effects, relevant to the treatment of NDs and especially AD and PD. The direct effects of clinoptilolite and its activated forms on AD pathology in vitro and in vivo are also reviewed, as well as the use of zeolites as biosensors and delivery systems related to PD.
Measurements of Nuclear Magnetic Shielding in Molecules
Authors: Jackowski Karol , Wilczek Marcin
Published: June 2024

The origin of nuclear magnetic shielding in diamagnetic molecules is discussed, pointing out various contributions to the shielding from electrons and the effects of intra- and intermolecular interactions. In NMR practice, chemical shifts are determined first as the measure of shielding in observed samples. The descriptions of shielding and chemical shifts are not fully consistent. Gas phase studies permit the withdrawal of intermolecular contributions from shielding and obtaining the magnetic shielding data in isolated molecules. The shielding determination in molecules is possible using at least three methods delivering the reference shielding standards for selected nuclei. The known shielding of one magnetic nucleus can be transferred to other nuclei if the appropriate nuclear magnetic moments are available with satisfactory accuracy. It is possible to determine the nuclear magnetic dipole moments using the most advanced ab initio shielding calculations jointly with the NMR frequencies measurements for small-sized isolated molecules. Helium-3 gas is postulated as all the molecules’ primary and universal reference standard of shielding. It can be easily applied using common deuterium lock solvents as the secondary reference standards. The measurements of absolute shielding are available for everyone with the use of standard NMR spectrometers.
Homo- and Heterogeneous Benzyl Alcohol Catalytic Oxidation Promoted by Mononuclear Copper(II) Complexes: The Influence of the Ligand upon Product Conversion
Authors: Chimilouski Larissa , Slominski William H. , Tillmann Ana I. , Will Daniella , dos Santos Aaron M. , Farias Giliandro , Martendal Edmar , Naidek Karine P. , Xavier Fernando R.
Published: June 2024

The catalytic properties of three copper complexes, [Cu(en)2](ClO4)2 (1), [Cu(amp)2](ClO4)2, (2) and [Cu(bpy)2](ClO4)2 (3) (where en = ethylenediamine, amp = 2-aminomethylpyridine and bpy = 2,2′-bipyridine), were explored upon the oxidation of benzyl alcohol (BnOH). Maximized conversions of the substrates to their respective products were obtained using a multivariate analysis approach, a powerful tool that allowed multiple variables to be optimized simultaneously, thus creating a more economical, fast and effective technique. Considering the studies in a fluid solution (homogeneous), all complexes strongly depended on the amount of the oxidizing agent (H2O2), followed by the catalyst load. In contrast, time seemed to be statistically less relevant for complexes 1 and 3 and not relevant for 2. All complexes showed high selectivity in their optimized conditions, and only benzaldehyde (BA) was obtained as a viable product. Quantitatively, the catalytic activity observed was 3 > 2 > 1, which is related to the π-acceptor character of the ligands employed in the study. Density functional theory (DFT) studies could corroborate this feature by correlating the geometric index for square pyramid Cu(II)-OOH species, which should be generated in the solution during the catalytic process. Complex 3 was successfully immobilized in silica-coated magnetic nanoparticles (Fe3O4@SiO2), and its oxidative activity was evaluated through heterogenous catalysis assays. Substrate conversion promoted by 3-Fe3O4@SiO2 generated only BA as a viable product, and the supported catalyst’s recyclability was proven. Reduced catalytic conversions in the presence of the radical scavenger (2,2,6,6-tetrametil-piperidi-1-nil)oxil (TEMPO) indicate that radical and non-radical mechanisms are involved.
Decoding the κ Opioid Receptor (KOR): Advancements in Structural Understanding and Implications for Opioid Analgesic Development
Authors: Li Zoe , Huang Ruili , Xia Menghang , Chang Nancy , Guo Wenjing , Liu Jie , Dong Fan , Liu Bailang , Varghese Ann , Aslam Aasma , Patterson Tucker A. , Hong Huixiao
Published: June 2024

The opioid crisis in the United States is a significant public health issue, with a nearly threefold increase in opioid-related fatalities between 1999 and 2014. In response to this crisis, society has made numerous efforts to mitigate its impact. Recent advancements in understanding the structural intricacies of the κ opioid receptor (KOR) have improved our knowledge of how opioids interact with their receptors, triggering downstream signaling pathways that lead to pain relief. This review concentrates on the KOR, offering crucial structural insights into the binding mechanisms of both agonists and antagonists to the receptor. Through comparative analysis of the atomic details of the binding site, distinct interactions specific to agonists and antagonists have been identified. These insights not only enhance our understanding of ligand binding mechanisms but also shed light on potential pathways for developing new opioid analgesics with an improved risk-benefit profile.
A Comprehensive Review of Hollow-Fiber Membrane Fabrication Methods across Biomedical, Biotechnological, and Environmental Domains
Authors: Wojciechowski Cezary , Wasyłeczko Monika , Lewińska Dorota , Chwojnowski Andrzej
Published: June 2024

This work presents methods of obtaining polymeric hollow-fiber membranes produced via the dry–wet phase inversion method that were published in renowned specialized membrane publications in the years 2010–2020. Obtaining hollow-fiber membranes, unlike flat membranes, requires the use of a special installation for their production, the most important component of which is the hollow fiber forming spinneret. This method is most often used in obtaining membranes made of polysulfone, polyethersulfone, polyurethane, cellulose acetate, and its derivatives. Many factors affect the properties of the membranes obtained. By changing the parameters of the spinning process, we change the thickness of the membranes’ walls and the diameter of the hollow fibers, which causes changes in the membranes’ structure and, as a consequence, changes in their transport/separation parameters. The type of bore fluid affects the porosity of the inner epidermal layer or causes its atrophy. Porogenic compounds such as polyvinylpyrrolidones and polyethylene glycols and other substances that additionally increase the membrane porosity are often added to the polymer solution. Another example is a blend of two- or multi-component membranes and dual-layer membranes that are obtained using a three-nozzle spinneret. In dual-layer membranes, one layer is the membrane scaffolding, and the other is the separation layer. Also, the temperature during the process, the humidity, and the composition of the solution in the coagulating bath have impact on the parameters of the membranes obtained.
Communicating Arteries and Leptomeningeal Collaterals: A Synergistic but Independent Effect on Patient Outcomes after Stroke
Authors: Sablić Sara , Dolić Krešimir , Budimir Mršić Danijela , Čičmir-Vestić Mate , Matana Antonela , Lovrić Kojundžić Sanja , Marinović Guić Maja
Published: June 2024

The collateral system is a compensatory mechanism activated in the acute phase of an ischemic stroke. It increases brain perfusion to the hypoperfused area. Arteries of the Willis’ circle supply antegrade blood flow, while pial (leptomeningeal) arteries direct blood via retrograde flow. The aim of our retrospective study was to investigate the relationship between both collateral systems, computed tomography perfusion (CTP) values, and functional outcomes in acute stroke patients. Overall, 158 patients with anterior circulation stroke who underwent mechanical thrombectomy were included in the study. We analyzed the presence of communicating arteries and leptomeningeal arteries on computed tomography angiography. Patients were divided into three groups according to their collateral status. The main outcomes were the rate of functional independence 3 months after stroke (modified Rankin scale score, mRS) and mortality rate. Our study suggests that the collateral status, as indicated by the three groups (unfavorable, intermediate, and favorable), is linked to CT perfusion parameters, potential recuperation ratio, and stroke outcomes. Patients with favorable collateral status exhibited smaller core infarct and penumbra volumes, higher mismatch ratios, better potential for recuperation, and improved functional outcomes compared to patients with unfavorable or intermediate collateral status.
Spectral Index-Based Estimation of Total Nitrogen in Forage Maize: A Comparative Analysis of Machine Learning Algorithms
Authors: Martínez-Sifuentes Aldo Rafael , Trucíos-Caciano Ramón , López-Hernández Nuria Aide , Miguel-Valle Enrique , Estrada-Ávalos Juan
Published: June 2024

Nitrogen plays a fundamental role as a nutrient for the growth of leaves and the process of photosynthesis, as it directly influences the quality and yield of corn. The importance of knowing the foliar nitrogen content through Machine Learning algorithms will help determine the efficient use of nitrogen fertilization in a context of sustainable agronomic management by avoiding Nitrogen loss and preventing it from becoming a pollutant for the soil and the atmosphere. The combination of machine learning algorithms with vegetation spectral indices is a new practice that helps estimate parameters of agricultural importance such as nitrogen. The objective of the present study was to compare random forest and neural network algorithms for estimating total plant nitrogen with spectral indices. Five spectral indices were obtained from remotely piloted aircraft systems and analyzed by mean, maximum and minimum from each sample plot to finally obtain 15 indices, and total nitrogen was estimated from the georeferenced points. The most important variables were selected with backward, forward and stepwise methods and total nitrogen estimates by laboratory were compared with random forest models and artificial neural networks. The most important indices were NDREmax and TCARImax. Using 15 spectral indices, total nitrogen with a variance of 79% and 81% with random forest and artificial neural network, respectively, was estimated. And only using NDREmax and TCARmax indices, 73% and 79% were explained by random forest and artificial neural network, respectively. It is concluded that it is possible to estimate nitrogen in forage maize with two indices and it is recommended to analyze by phenological stage and with a greater number of field data.
The Effects of Breastfeeding on Childhood Behavioral and Emotional Development: A Prospective Cohort Study in China
Authors: Meng Ying , Yu Hongzhao , Zhang Mingxuan , Li Hongtian , Zhou Yubo , Liu Jianmeng
Published: June 2024

Background: Breastfeeding could improve a child’s health early on, but its long-term effects on childhood behavioral and emotional development remain inconclusive. We aimed to estimate the associations of feeding practice with childhood behavioral and emotional development. Methods: In this population-based birth cohort study, data on feeding patterns for the first 6 mo of life, the duration of breastfeeding, and children’s emotional and behavioral outcomes were prospectively collected from 2489 mother–child dyads. Feeding patterns for the first 6 mo included exclusive breastfeeding (EBF) and non-exclusive breastfeeding (non-EBF, including mixed feeding or formula feeding), and the duration of breastfeeding (EBF or mixed feeding) was categorized into ≤6 mo, 7–12 mo, 13–18 mo, and >18 mo. Externalizing problems and internalizing problems were assessed with the Child Behavior Checklist (CBCL) and operationalized according to recommended clinical cutoffs, corresponding to T scores ≥64. Multivariable linear regression and logistic regression were used to evaluate the association of feeding practice with CBCL outcomes. Results: The median (interquartile range) age of children at the outcome measurement was 32.0 (17.0) mo. Compared with non-EBF for the first 6 mo, EBF was associated with a lower T score of internalizing problems [adjusted mean difference (aMD): −1.31; 95% confidence interval (95% CI): −2.53, −0.10], and it was marginally associated with T scores of externalizing problems (aMD: −0.88; 95% CI: −1.92, 0.15). When dichotomized, EBF versus non-EBF was associated with a lower risk of externalizing problems (aOR: 0.54, 95% CI: 0.34, 0.87), and it was marginally associated with internalizing problems (aOR: 0.75, 95% CI: 0.54, 1.06). Regarding the duration of breastfeeding, breastfeeding for 13–18 mo versus ≤6 mo was associated with lower T scores of internalizing problems (aMD: −2.50; 95% CI: −4.43, −0.56) and externalizing problems (aMD: −2.75; 95% CI: −4.40, −1.10), and breastfeeding for >18 mo versus ≤6 mo was associated with lower T scores of externalizing problems (aMD: −1.88; 95% CI: −3.68, −0.08). When dichotomized, breastfeeding for periods of 7–12 mo, 13–18 mo, and >18 mo was associated with lower risks of externalizing problems [aOR (95% CI): 0.96 (0.92, 0.99), 0.94 (0.91, 0.98), 0.96 (0.92, 0.99), respectively]. Conclusions: Exclusive breastfeeding for the first 6 mo and a longer duration of breastfeeding, exclusively or partially, are beneficial for childhood behavioral and emotional development.
Design and Validation of MEDOC, a Tool to Assess the Combined Adherence to Mediterranean and Western Dietary Patterns
Authors: Mazzucca Camilla Barbero , Scotti Lorenza , Raineri Davide , Cappellano Giuseppe , Chiocchetti Annalisa
Published: June 2024

The Mediterranean diet (MD) and Western diet (WD) are poles apart as dietary patterns. Despite the availability of epidemiological tools to estimate the adherence to MD, to date, there is a lack of combined scores. We developed MEDOC, a food frequency questionnaire (FFQ) designed to calculate a combined adherence score for both diets and validated it on 213 subjects. The test–retest reliability revealed all frequency questions falling within the acceptable range of 0.5 to 0.7 (Pearson correlation coefficient) in younger (<30 years old) subjects, while 1 question out of 39 fell below the range in older (>30 years old) participants. The reproducibility for portion size was less satisfying, with, respectively, 38.2% and 70.5% of questions falling below 0.5 (Cohen’s Kappa index) for younger and older subjects. The good correlation (R = 0.63, p < 0.0001 for subjects younger than 30 years and R = 0.54, p < 0.0001 for subjects older than 30 years, Pearson’s correlation coefficient) between the MEDOC score and the MediDietScore (MDS) confirmed the validity of the MEDOC score in identifying patients who adhere to the MD. Harnessing the capabilities of this innovative tool, we aim to broaden the existing perspective to study complex dietary patterns in nutritional epidemiology studies.
Health Behaviours and the Quality of Life of Students of Medical Fields during the COVID-19 Pandemic
Authors: Kupcewicz Ewa , Schneider-Matyka Daria , Rachubińska Kamila , Jastrzębski Paweł , Bentkowska Aleksandra , Grochans Elżbieta
Published: June 2024

(1) Background: Social distancing and closing down public spaces associated with learning, leisure and physical activity limited the spread of COVID-19. These measures had an impact not only on the economy and education but also on health behaviours and the quality of life of individuals affected by the restrictions. The aim of this study was to identify the role of health behaviours in the perception of the quality of life of students during the COVID-19 pandemic. (2) Methods: This study was conducted among 796 students of the University of Warmia and Mazury in Olsztyn in the first quarter of 2022. Subgroup 1 consisted of students at the Public Health School (n = 428; 53.8%) and subgroup 2 consisted of students belonging to the Faculty of Veterinary Medicine (n = 368; 46.2%). The diagnostic survey method was applied, and an original survey questionnaire, the Health Behaviour Inventory and the Quality of Life Questionnaire (WHOQoL-Bref version) were used. (3) Results: The largest contribution to the prediction of quality of life of students in subgroup 1 was made by a positive mental attitude related to avoiding too strong emotions, which explained 19% of the result variability in the somatic domain (ßeta = 0.24; R2 = 0.21), 20% of the result variability in the psychological domain (ßeta = 0.36; R2 = 0.20), 16% of the result variability in the social domain (ßeta = 0.52; R2 = 0.17) and 17% of the result variability in the environmental domain (ßeta = 0.19; R2 = 0.19). Moreover, in subgroup 2, a predominantly positive mental attitude significantly predicted quality of life in the somatic domain, explaining 23% of the result variability (ßeta = 0.24; R2 = 0.26), while it explained 25% of the result variability in the psychological domain (ßeta = 0.47; R2 = 0.25), 16% of the result variability in the social domain (ßeta = 0.46; R2 = 0.17) and 21% of the result variability in the environmental domain (ßeta = 0.38; R2 = 0.23). (4) Conclusions: Positive correlations between health behaviours and the quality of life among the study participants were determined. Health-promoting behaviours had a beneficial impact on the respondents’ quality of life during the COVID-19 pandemic. The category of health behaviours described as a positive mental attitude was an important predictor for the participants’ quality of life.
The Prognostic Role of Prognostic Nutritional Index and Controlling Nutritional Status in Predicting Survival in Older Adults with Oncological Disease: A Systematic Review
Authors: Ferreira Ana Filipa , Fernandes Tatiana , Carvalho Maria do Carmo , Loureiro Helena Soares
Published: June 2024

The increase in new cancer diagnoses in the elderly calls for new, accessible, and easy-to-use prognostic tools that contribute to lowering the burden of the disease. Recognising the importance of inflammation and nutritional status in the progression of the disease, the purpose of this systematic review was to synthesise the evidence on the prognostic role of Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) in predicting survival of older adult cancer patients. A comprehensive search was conducted in PubMed and Web of Science Core Collection databases until 22 February 2024. The articles included in this review (n = 38) examined the relationships of PNI and CONUT with survival outcomes in elderly cancer patients. Despite high heterogeneity between the studies, most concluded that low PNI values are associated with poor overall survival (OS), particularly in gastric cancer patients. Most studies did not find an association between PNI and cancer-specific survival, progression-free survival, disease-free survival, recurrence-free survival, and mortality. Results regarding the prognostic role of CONUT in predicting survival were inconclusive. This study suggests that PNI could be used to predict OS in elderly cancer patients, while more studies are needed to assess the prognostic role of CONUT.
Technology Readiness Level Roadmap for Developing Innovative Herbal Medicinal Products
Authors: Pagani Eduardo , Ropke Cristina Dislich , Soares Cristiane Mota , Perez Sandra Aurora Chavez , Benevides Paulo José Coelho , Barbosa Barbara Sena , Carvalho Ana Cecilia Bezerra , Behrens Maria Dutra
Published: June 2024

Despite the vast global botanical diversity, the pharmaceutical development of herbal medicinal products (HMPs) remains underexploited. Of over 370,000 described plant species, only a few hundred are utilized in HMPs. Most of these have originated from traditional use, and only a minority come from megadiverse countries. Exploiting the pharmacological synergies of the hundreds of compounds found in poorly studied plant species may unlock new therapeutic possibilities, enhance megadiverse countries’ scientific and socio-economic development, and help conserve biodiversity. However, extensive constraints in the development process of HMPs pose significant barriers to transforming this unsatisfactory socio-economic landscape. This paper proposes a roadmap to overcome these challenges, based on the technology readiness levels (TRLs) introduced by NASA to assess the maturity of technologies. It aims to assist research entities, manufacturers, and funding agencies from megadiverse countries in the discovery, development, and global market authorization of innovative HMPs that comply with regulatory standards from ANVISA, EMA, and FDA, as well as WHO and ICH guidelines.
Oral Administration of Nacre Extract from Pearl Oyster Shells Has Anti-Aging Effects on Skin and Muscle, and Extends the Lifespan in SAMP8 Mice
Authors: Yamamoto Hana , Shimomura Nanami , Hasegawa Yasushi
Published: June 2024

Pearl oysters have been extensively utilized in pearl production; however, most pearl oyster shells are discarded as industrial waste. In a previous study, we demonstrated that the intraperitoneal administration of pearl oyster shell-derived nacre extract (NE) prevented d-galactose-induced brain and skin aging. In this study, we examined the anti-aging effects of orally administered NE in senescence-accelerated mice (SAMP8). Feeding SAMP8 mice NE prevented the development of aging-related characteristics, such as coarse and dull hair, which are commonly observed in aged mice. Additionally, the NE mitigated muscle aging in SAMP8 mice, such as a decline in grip strength. Histological analysis of skeletal muscle revealed that the NE suppressed the expression of aging markers, cyclin-dependent kinase inhibitor 2A (p16) and cyclin-dependent kinase inhibitor 1 (p21), and increased the expression of sirtuin1 and peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1)- α, which are involved in muscle synthesis. These findings suggest that the oral administration of NE suppresses skeletal muscle aging. Moreover, NE administration suppressed skin aging, including a decline in water content. Interestingly, oral administration of NE significantly extended the lifespan of SAMP8 mice, suggesting that its effectiveness as an anti-aging agent of various tissues including skeletal muscle, skin, and adipose tissue.
Photodynamic Therapy for Atherosclerosis: Past, Present, and Future
Authors: Lin Yanqing , Xie Ruosen , Yu Tao
Published: June 2024

This review paper examines the evolution of photodynamic therapy (PDT) as a novel, minimally invasive strategy for treating atherosclerosis, a leading global health concern. Atherosclerosis is characterized by the accumulation of lipids and inflammation within arterial walls, leading to significant morbidity and mortality through cardiovascular diseases such as myocardial infarction and stroke. Traditional therapeutic approaches have primarily focused on modulating risk factors such as hypertension and hyperlipidemia, with emerging evidence highlighting the pivotal role of inflammation. PDT, leveraging a photosensitizer, specific-wavelength light, and oxygen, offers targeted treatment by inducing cell death in diseased tissues while sparing healthy ones. This specificity, combined with advancements in nanoparticle technology for improved delivery, positions PDT as a promising alternative to traditional interventions. The review explores the mechanistic basis of PDT, its efficacy in preclinical studies, and the potential for enhancing plaque stability and reducing macrophage density within plaques. It also addresses the need for further research to optimize treatment parameters, mitigate adverse effects, and validate long-term outcomes. By detailing past developments, current progress, and future directions, this paper aims to highlight PDT’s potential in revolutionizing atherosclerosis treatment, bridging the gap from experimental research to clinical application.
Review of Prodrug and Nanodelivery Strategies to Improve the Treatment of Colorectal Cancer with Fluoropyrimidine Drugs
Authors: Sarkar Santu , Kiren Sezgin , Gmeiner William H.
Published: June 2024

Fluoropyrimidine (FP) drugs are central components of combination chemotherapy regimens for the treatment of colorectal cancer (CRC). FP-based chemotherapy has improved survival outcomes over the last several decades with much of the therapeutic benefit derived from the optimization of dose and delivery. To provide further advances in therapeutic efficacy, next-generation prodrugs and nanodelivery systems for FPs are being developed. This review focuses on recent innovative nanodelivery approaches for FP drugs that display therapeutic promise. We summarize established, clinically useful FP prodrug strategies, including capecitabine, which exploit tumor-specific enzyme expression for optimal anticancer activity. We then describe the use of FP DNA-based polymers (e.g., CF10) for the delivery of activated FP nucleotides as a nanodelivery approach with proven activity in pre-clinical models and with clinical potential. Multiple nanodelivery systems for FP delivery show promise in CRC pre-clinical models and we review advances in albumin-mediated FP delivery, the development of mesoporous silica nanoparticles, emulsion-based nanoparticles, metal nanoparticles, hydrogel-based delivery, and liposomes and lipid nanoparticles that display particular promise for therapeutic development. Nanodelivery of FPs is anticipated to impact CRC treatment in the coming years and to improve survival for cancer patients.
Liquid Chromatography-Mass Spectrometry Analytical Methods for the Quantitation of p-Cresol Sulfate and Indoxyl Sulfate in Human Matrices: Biological Applications and Diagnostic Potentials
Authors: Al-Dajani Ala’a R. , Hou Qi Kun , Kiang Tony K. L.
Published: June 2024

Indoxyl sulfate (IxS) and p-cresyl sulfate (pCS) are toxic uremic compounds with documented pathological outcomes. This review critically and comprehensively analyzes the available liquid chromatography-mass spectrometry methods quantifying IxS and pCS in human matrices and the biological applications of these validated assays. Embase, Medline, PubMed, Scopus, and Web of Science were searched until December 2023 to identify assays with complete analytical and validation data (N = 23). Subsequently, citation analysis with PubMed and Scopus was utilized to identify the biological applications for these assays (N = 45). The extraction methods, mobile phase compositions, chromatography, and ionization methods were evaluated with respect to overall assay performance (e.g., sensitivity, separation, interference). Most of the assays focused on human serum/plasma, utilizing acetonitrile or methanol (with ammonium acetate/formate or formic/acetic acid), liquid–liquid extraction, reverse phase (e.g., C18) chromatography, and gradient elution for analyte separation. Mass spectrometry conditions were also consistent in the identified papers, with negative electrospray ionization, select multiple reaction monitoring transitions and deuterated internal standards being the most common approaches. The validated biological applications indicated IxS and/or pCS were correlated with renal disease progression and cardiovascular outcomes, with limited data on central nervous system disorders. Methods for reducing IxS and/or pCS concentrations were also identified (e.g., drugs, natural products, diet, dialysis, transplantation) where inconsistent findings have been reported. The clinical monitoring of IxS and pCS is gaining significant interest, and this review will serve as a useful compendium for scientists and clinicians.
Comprehensive Insight into Cutaneous Application of Hemp
Authors: Žugić Ana , Martinović Milica , Tadić Vanja , Rajković Miloš , Racić Gordana , Nešić Ivana , Koren Anamarija
Published: June 2024

Known for its natural bio-compounds and therapeutic properties, hemp is being utilized in the development of skin products. These products offer a wide range of applications and benefits in the fields of natural bio-compounds, pharmaceutical technology, topical delivery systems, and cosmeceuticals. This manuscript deals with hemp actives, such as cannabinoids, terpenes, and flavonoids, and their diverse biological properties relative to topical application, including anti-inflammatory, antimicrobial, and antioxidant effects. Also, the paper reviews strategies to overcome poor penetration of hemp actives, as well as the integration of hemp actives in cosmeceuticals that provide natural and sustainable alternatives to traditional skincare products offering a range of benefits, including anti-aging, moisturizing, and soothing properties. The review aims to provide a comprehensive understanding of the development and manufacturing processes of skin products containing hemp actives. By delving into the science behind hemp-based products, the paper provides valuable insights into the potential of hemp as a versatile ingredient in the pharmaceutical and cosmetic industries. The utilization of hemp in these innovative products not only offers therapeutic benefits but also promotes natural and sustainable approaches to skincare.
Design and Biocompatibility of Biodegradable Poly(octamethylene suberate) Nanoparticles to Treat Skin Diseases
Authors: de Barros Dragana P. C. , Fonseca Luís P. , Gonçalves Luís G. , Serrano Diogo S. , Oliva Abel
Published: June 2024

Biodegradable aliphatic polyester formulations as carriers for topical drug delivery show the potential to encapsulate structurally different therapeutic compounds. Poly(octamethylene suberate) (POS) nanoparticles (POS-NPs) were used as a matrix to encapsulate four therapeutic molecules used to treat skin disorders: caffeine (CF), quercetin (QR), hydrocortisone (HC), and adapalene (AD). Hydrophobicity and chemical structure of bioactive compounds (BCs) influenced the physicochemical stability of drug-loaded nanoparticles. The particle size of drug-loaded nanoparticles was between 254.9 nm for the CF-POS-NP and 1291.3 for QR-POS-NP. Particles had a negative charge from −27.6 mV (QR) to −49.2 mV (HC). Drug loading content for all BC-POS-NPs varies between 36.11 ± 1.48% (CF-POS-NP) and 66.66 ± 4.87% (AD-POS-NP), and their entrapment efficiency is relatively high (28.30 ± 1.81% and 99.95 ± 0.04%, respectively). Calorimetric analysis showed the appearance of polymorphism for AD- and HC-loaded systems and the drug’s complete solubilisation into all nanoparticle formulations. FTIR and NMR spectra showed apparent drug incorporation into the polymer matrix of NPs. The encapsulation of BCs enhanced the antioxidative effect. The prepared POS nanoparticles’ cytotoxicity was studied using two dermal cell lines, keratinocyte (HaCaT) cells and fibroblasts (HDFn). The nanoparticle cytotoxic effect was more substantial on HaCaT cell lines. A reconstructed human epidermis (RHE) was successfully used to investigate the penetration of polymeric NPs. Based on permeation and histology studies, HC-POS-NPs and CF-POS-NPs were shown not to be suitable for dermal applications with the explored drug concentrations. AD presents a high permeation rate and no toxic impact on RHE.
Challenges and the Way Forward in Demand-Forecasting Practices within the Ethiopian Public Pharmaceutical Supply Chain
Authors: Bilal Arebu Issa , Bititci Umit Sezer , Fenta Teferi Gedif
Published: June 2024

This study delves into the challenges of pharmaceutical forecasting within the Ethiopian public pharmaceutical supply chain, which is vital for ensuring medicine availability and optimizing healthcare delivery. t It aims to identify and analyze key hindrances to pharmaceutical forecasting in Ethiopia, employing qualitative analysis through semi-structured interviews with stakeholders. Thematic analysis using NVIVO 14 software reveals challenges including finance-related constraints, workforce shortages, and data quality issues. Financial challenges arise from funding uncertainties, causing delayed procurement and stockouts. Workforce shortages hinder accurate forecasting, while data quality issues result from incomplete and untimely reporting. Recommendations include prioritizing healthcare financing, investing in workforce development, and improving data quality through technological advancements and enhanced coordination among stakeholders.
Principles of Measuring Thickness and Refractive Index of Thin Dielectric Film by Using Multiresonance Archimedean Spiral Metasurfaces with C Resonator in the Terahertz Frequency Range
Authors: Kameshkov Oleg , Gerasimov Vasily
Published: June 2024

Metasurfaces are an excellent platform for terahertz (THz) sensing applications, enabling highly efficient light–matter interaction and overcoming the fundamental disadvantage of the relatively long-wavelength THz range (30–3000 μm), which limits sensing of small features. The current focus in developing metasurfaces is mostly directed toward single-resonance metasurfaces and reconstruction of the dielectric constants of analyte from the saturation mode induced by the limited sensing volume of the metasurface. This paper presents a numerical demonstration of using a multiresonance metasurface to extract the thickness and refractive index of a deposited film without saturation of the sensor. It was shown that the multiresonance property enables determination of the analyte characteristic via measurements with two different thicknesses and tracking changes in two resonances. High-accuracy parameter retrieval is achieved when there are large differences in the thicknesses. In contrast to the established approach, this method provides an efficient way to avoid using relatively thick films.
Increase in Modulation Speed of Silicon Photonics Modulator with Quantum-Well Slab Wings: New Insights from a Numerical Study
Authors: Ogawa Kensuke
Published: June 2024

A Silicon Photonics modulator is a high-speed photonic integrated circuit for optical data transmission in high-capacity optical networks. Silicon Photonics modulators in the configuration of a Mach–Zehnder interferometer, in which a PN-junction rib-waveguide phase shifter is inserted in each arm of the interferometer, are studied in this paper because of their superior performance of high-quality optical data generation in a wide range of spectral bands and their simplicity in fabrication processes suitable to production in foundries. Design, fabrication, and fundamental characteristics of Silicon Photonics Mach–Zehnder modulators are reviewed as an introduction to these high-speed PICs on the Silicon Photonics platform. Modulation speed, or modulation bandwidth, is a key performance item, as well as optical loss, in the application to high-speed optical transmitters. Limiting factors on modulation speed are addressed in equations. Electrical resistance–capacitance coupling, which causes optical modulation bandwidth–optical loss trade-off, is the most challenging limiting factor that limits high-speed modulation. Expansion of modulation bandwidth is not possible without increasing optical loss in the conventional approaches. A new idea including quantum-mechanical effect in the design of Silicon Photonics modulators is proposed and proved in computational analysis to resolve the bandwidth loss trade-off. By adding high-mobility quantum-well overlayers to the side slab wings of the rib-waveguide phase shifter, the modulation bandwidth is doubled without increasing optical loss to achieve a 200 Gbaud modulation rate.
Supercritical Impregnation of PETG with Olea europaea Leaf Extract: Influence of Operational Parameters on Expansion Degree, Antioxidant and Mechanical Properties
Authors: Machado Noelia D. , Mosquera José E. , Cejudo-Bastante Cristina , Goñi María L. , Martini Raquel E. , Gañán Nicolás A. , Mantell-Serrano Casimiro , Casas-Cardoso Lourdes
Published: June 2024

PETG (poly(ethylene glycol-co-cyclohexane-1,4-dimethanol terephthalate)) is an amorphous copolymer, biocompatible, recyclable, and versatile. Nowadays, it is being actively researched for biomedical applications. However, proposals of PETG as a platform for the loading of bioactive compounds from natural extract are scarce, as well as the effect of the supercritical impregnation on this polymer. In this work, the supercritical impregnation of PETG filaments with Olea europaea leaf extract was investigated, evaluating the effect of pressure (100–400 bar), temperature (35–55 °C), and depressurization rate (5–50 bar min−1) on the expansion degree, antioxidant activity, and mechanical properties of the resulting filaments. PETG expansion degree ranged from ~3 to 120%, with antioxidant loading ranging from 2.28 to 17.96 g per 100 g of polymer, corresponding to oxidation inhibition values of 7.65 and 66.55%, respectively. The temperature and the binary interaction between pressure and depressurization rate most affected these properties. The mechanical properties of PETG filaments depended greatly on process variables. Tensile strength values were similar or lower than the untreated filaments. Young’s modulus and elongation at break values decreased below ~1000 MPa and ~10%, respectively, after the scCO2 treatment and impregnation. The extent of this decrease depended on the supercritical operational parameters. Therefore, filaments with higher antioxidant activity and different expansion degrees and mechanical properties were obtained by adjusting the supercritical processing conditions.
In Situ Synthesis of CsPbX3/Polyacrylonitrile Nanofibers with Water-Stability and Color-Tunability for Anti-Counterfeiting and LEDs
Authors: Shi Yinbiao , Su Xiaojia , Wang Xiaoyan , Ding Mingye
Published: June 2024

Inorganic CsPbX3 (X = Cl, Br, I) perovskite quantum dots (PQDs) have attracted widespread attention due to their excellent optical properties and extensive application prospects. However, their inherent structural instability significantly hinders their practical application despite their outstanding optical performance. To enhance stability, an in situ electrospinning strategy was used to synthesize CsPbX3/polyacrylonitrile composite nanofibers. By optimizing process parameters (e.g., halide ratio, electrospinning voltage, and heat treatment temperature), all-inorganic CsPbX3 PQDs have been successfully grown in a polyacrylonitrile (PAN) matrix. During the electrospinning process, the rapid solidification of electrospun fibers not only effectively constrained the formation of large-sized PQDs but also provided effective physical protection for PQDs, resulting in the improvement in the water stability of PQDs by minimizing external environmental interference. Even after storage in water for over 100 days, the PQDs maintained approximately 93.5% of their photoluminescence intensity. Through the adjustment of halogen elements, the as-obtained composite nanofibers exhibited color-tunable luminescence in the visible light region, and based on this, a series of multicolor anti-counterfeiting patterns were fabricated. Additionally, benefiting from the excellent water stability and optical performance, the CsPbBr3/PAN composite film was combined with red-emitting K2SiF6:Mn4+ (KSF) on a blue LED (460 nm), producing a stable and efficient WLED device with a color temperature of around 6000 K and CIE coordinates of (0.318, 0.322). These results provide a general approach to synthesizing PQDs/polymer nanocomposites with excellent water stability and multicolor emission, thereby promoting their practical applications in multifunctional optoelectronic devices and advanced anti-counterfeiting.